May 23, 2024 • 33 mins
Embark on a scientific odyssey with us as we reveal the hidden ties between our genetic blueprints and the scales. With expertise in molecular biology and genetics, Dr. Iliakova dives into the nuanced interplay between DNA and obesity, breaking down myths and simplifying science. Discover rare genetic syndromes and their surprising implications for our understanding of weight regulation. We also inspect groundbreaking medications targeting genetic factors in overeating, offering a sneak peek into the future of personalized obesity treatment.
Our journey doesn't stop at genetics; we traverse the complex terrain of hormones and their delicate dance with our weight. We unpack how obesity can disrupt this balance, affecting everything from fertility to metabolic health. Learn about the link between conditions like PCOS and hormonal harmony, and how thoughtful weight management can bolster fertility and overall well-being. Plus, we highlight cutting-edge treatments, from receptor agonists to the staggering potential of CRISPR gene editing and the transformative power of fecal transplants. Join us for this enlightening exploration of weight, health, and the pioneering science that's shaping our approach to both.
Our journey doesn't stop at genetics; we traverse the complex terrain of hormones and their delicate dance with our weight. We unpack how obesity can disrupt this balance, affecting everything from fertility to metabolic health. Learn about the link between conditions like PCOS and hormonal harmony, and how thoughtful weight management can bolster fertility and overall well-being. Plus, we highlight cutting-edge treatments, from receptor agonists to the staggering potential of CRISPR gene editing and the transformative power of fecal transplants. Join us for this enlightening exploration of weight, health, and the pioneering science that's shaping our approach to both.
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Transcript
Episode Transcript
Available transcripts are automatically generated. Complete accuracy is not guaranteed.
Speaker 1 (00:00):
Welcome to Core Bariatric's podcast, hosted by
bariatric surgeon Dr MariaIliakova and Tami LaCoste,
bariatric coordinator and apatient herself.
Our goal is building andelevating our community.
The Core Bariatric podcast doesnot offer medical advice,
diagnosis or treatment.
On this podcast, we aim toshare stories, support and
(00:22):
insight into the world beyondthe clinic.
Let's get into it, maria.
It's all.
Eat less, move more.
Right, that's it, that's all100%.
Speaker 2 (00:32):
Yes, it is all that.
Yes, 100%, tami.
Okay, why wouldn't you even ask?
Of course, ins and outs, hello.
Speaker 1 (00:42):
Because that's what everybody thinks.
Speaker 2 (00:44):
That is what everybody thinks and everybody's
wrong, anyway.
So no, but you're actuallyright.
So today we're going to bediving into genetics and weight
genetics and obesity.
And the reason why is becauseguess what, if it were simple,
everybody would not be asking us, not be wondering about this
and not be struggling with this,because we'd have it all
(01:05):
figured out.
If an after-waste killer in amile run was a mile run, we'd
all be the same size, exactly.
So I am always really curiousabout the why and the behind the
scenes, and I think you are too.
So I wanted to create a podcastepisode that was all about
genetics and obesity, and thereason why is because I actually
have a background in molecularbiology, genetics, studying
(01:27):
proteins, all that fun stuff.
What.
So I love this.
It is so exciting and I thinkyou're going to find that.
Speaker 1 (01:33):
Look, I've known you for how long and I did not know
that.
Speaker 2 (01:36):
Yeah, and so I am really jazzed about this.
Speaker 1 (01:39):
And you're 34.
Speaker 2 (01:41):
Well, you know, sometimes we do, sometimes
people have good childhoods andsometimes they have.
Speaker 1 (01:46):
actually I don't really get childhood, but I mean
I got three kids and I'm 30 andyou, just you have degrees and
you're 34.
Speaker 2 (01:54):
Yeah, so instead of having kids, I had degrees, and
so yes, anyway, but I am reallyreally jazzed about genetics and
about all of the ways that ourbodies actually regulate how
things work, and how thatchanges over time and how it
relates to weight is pretty, Ithink, fascinating.
So you're going to go on alittle bit of a journey with me
today.
Yes, please.
Hopefully we will not bore thepants off of everyone listening
(02:16):
today.
Speaker 1 (02:17):
I want to add that, so we're doing video.
Yes, maria is all dressed up ina minnowsuit shirt.
Speaker 2 (02:22):
Oh please, I'm just like a t-shirt.
I'm in a t-shirt, I'm in at-shirt.
Speaker 1 (02:26):
Well, red is your color.
Well, thank you Anyway genetics, yes, genetics.
Speaker 2 (02:29):
So anyway, let's talk real quick about weight and
metabolic change.
We have talked a lot about inother episodes the fact that
surgery and other ways thatpeople can lose weight can have
impacts on your signaling andimpacts on your metabolism, and
today we're going to talk intothe weeds a bit more about what
that means.
On a cell level, and evensmaller than the cell, is the
(02:51):
genes, and we're not talkingabout, like Levi's genes or gas
genes.
We're talking about the genesthat get expressed and create
all the different parts of yourbody, all the different cells
and all the different proteinsand all that.
But what do you Into the thickof it?
Into the thick of it, tammy,what do you know so far about
genes and weight, or genes andobesity?
Speaker 1 (03:13):
I know that most people that are obese their kids
are obese, their parents areobese there has to be a
connection there.
I love that.
Speaker 2 (03:25):
And, honestly, a lot of what we know about genetics
comes from those observations ofpeople going wait a second.
There's got to be some kind oflink here, because this runs in
families.
And actually I remember I hadone patient that was pretty
funny and I said what runs inyour family?
And they said nobody runs in myfamily and we laughed and we
had a great time, but anyway,but you're obviously right,
(03:45):
these things do run in familiesand, however do we do genetic
testing on a regular basis forour patients.
No no, we do not.
Speaker 1 (03:54):
I don't think anybody really does right, Because
genetic testing isn't covered byinsurance.
Speaker 2 (03:59):
Well, there's that.
We run into our age old themeof it's not covered by insurance
, yes, but here there's also abasis for that, because a lot of
weight isn't just genetics andisn't just known genetics,
meaning like we know exactlywhat gene is being affected, and
that's why people have weightstruggles or weight challenges
more than other people.
(04:19):
It's a lot more factors thanjust that and we're going to
talk about today some targets oftreatment, how things work on
the sort of gene and cell level,and basically what kind of
treatments exist now, and it's alittle bit about in the future
where things are going to.
So that's kind of how we'regoing to structure today.
So, yeah, there is actually onemedication on the market called
(04:43):
in Crevy or in Crevy, dependingon how you pronounce it, and
Sivri, I think some people sayto and it specifically targets
one gene that gets expressed andcan cause overeating or the
desire to overeat, and can causeobesity in some people.
Right, and I think we'veactually seen some of the reps
for that medication in our ownoffice before.
(05:05):
Yeah, the light bulb went off.
Sorry, that's right.
No, no, that's totally fine,and there is genetic testing
that can be done that theircompany actually covers at this
point for patients, yes.
However, that affects way lessthan 1% of people who have
excess weight or obesity, soit's not common, and that's kind
of the theme behind a lot ofthese things.
(05:26):
Let me just run through a listof a couple of things that can
be related to excess weight thatare genetic syndromes, and
those are things likemelanocortin for receptor
deficiency, which is what thatmedication targets, leptin
deficiency, leptin receptordeficiency, brain-derived
metropic factor deficiency andprohormone convertase 1
(05:47):
deficiency, cohen syndrome,bartopetal syndrome, beckwith
Wiedemann syndrome, and there'smore.
I won't go through all of them,but there's over a dozen
different syndromes and specificgenes that are thought to be
directly related to obesity.
All together, all of thosethings, all the more than dozen
(06:08):
of those syndromes and specificmutations still account for less
than 1% of obesity.
So it's still 99% of the time.
There's still way more factorsthan just genetics involved.
So one big takeaway is, yes, itcan be genetics, but oftentimes
it's not just genetics, but westill need to look at it Exactly
(06:31):
.
So I think if you're havingsomeone who isn't, for instance,
like from a healthcareperspective, if you have someone
who is trying everything,including surgery, they're still
not losing weight.
They're trying medications,they're still not losing weight.
Or you have a kid, for instance, under the age of 16, who's
having a lot of issues withweight, even though their diet
and exercise is well-controlled.
They don't have really haveother medical conditions.
(06:52):
Really really important toconsider some of these syndromes
and genetic considerations.
So things to think about.
So when we're talking aboutadults, yeah, these things are
pretty rare.
Speaker 1 (07:03):
So I'm just thinking about someone in our family.
The mom and dad are not big.
The man is very big and notlike he's very active, he's on a
paving crew, it's a very active, he's just big guy, and his son
, who is only 12, baseball, allthe things very big.
(07:24):
But how did we get from two notso big people, sure, to a son
who is very large and then agrandson that is very large?
It just makes me think.
Speaker 2 (07:35):
Absolutely.
That's a good way to thinkabout it, because sometimes, if
it is genetics that is playing arole, those don't necessarily
get expressed in everygeneration.
So, if you think about it, yeah, you don't have to look further
.
Yeah, if you think about it,you can actually like dwarfism,
for instance, being a dwarf andI hope I am not saying anything
that is offending anyone.
This is just sort of somethingpeople are aware of.
(07:56):
You can actually havecompletely regular adult-sized
parents and have a dwarf child,or vice versa, you can have a
dwarf parent and still have aregular-sized child from, yeah,
depending on who they mate with.
So not all genes, even ifinherited, and gene mutations,
(08:18):
are expressed and not everythingis just straight heredity Like
your parents have this andtherefore you have this and
therefore your kids will havethis.
It also depends on who yourpartner is when you have a child
and it depends on what theirgenetics are and it depends on
what's dominant and what'srecessive, what gets expressed
more than other things, and whatgets masked by having a
(08:38):
dominant gene that getsexpressed instead.
So, for fear of getting toointo the weeds on this one,
suffice it to say that there's alot of different targets, in
fact, over 60 different genesthat are thought to have an
impact on people's weight andmetabolism, and they control a
lot of the same pathways that weactually target with
(08:59):
medications and with surgery.
So, interestingly enough, wewere talking in another episode
about how surgery works and wewere talking about like PI3K
pathways and leptin and ghrelinand GLP1s and things like that.
And guess what?
Those are the same kind oftargets, that the same kinds of
genes and the same kinds ofpathways that affect weight to
(09:19):
begin with.
So the very things that we'retargeting with medications and
surgery or other approaches arealso things that contribute to
what someone weighs.
Speaker 1 (09:28):
All right, it all comes together.
Speaker 2 (09:30):
It all comes together eventually, and there are a
couple of things that are prettyinteresting just as a global,
so big picture here.
When people have extra weight,especially weight over a BMI of
30, typically you can actuallycause the cells to behave
differently than they wouldotherwise.
So some stem cells are not asstrong, essentially, as others
(09:55):
in this situation, and so theydon't different, they don't
become as many cells as well asthey do in people who have BMI
under 30, for instance, and whatthat leads to is think of it
this way you have a pool of goo,and that goo can become brain
cells, it can become heart cells, it can become muscle cells, it
can become bone cells or jointcells or something like that.
(10:17):
When your weight, when your BMI, is over 30, the ability for
those cells to become healthy,adult cells that are these
different kinds is less.
So even the ability to heal andespecially when you're
recovering from injury, traumasurgery, those kinds of things
is less good at higher weightsthan it is at lower weights on
(10:38):
average.
So that's, I think, kind ofinteresting and that's
absolutely yeah it very much sois.
And that's impacted by genetics, but it's also impacted by how
those genes are gettingexpressed, and we'll get into
something called epigenetics,which is one level above
genetics.
So not even what genes you have, but how they're actually
getting used in the real bodyand how they're, whether they're
(10:59):
showing up or whether they'rebeing masked, is something that
happens on a day to day basis,on a minute to minute, second to
second basis, in all of ourbodies at all time.
Very interesting stuff?
No, it is.
It is so, moving on from there,there's also something called
genomic instability, and that'snot like being psycho or
unstable or a little different.
(11:19):
I got that.
Oh well, we all got that, so Iget it.
But genomic instability isbasically when genes are in an
environment to stay what theyare without any further changes
and they can be then used to beexpressed in a certain way
without changes.
When there's instability, itmeans that the genes that you
have even can be changedactively, and that change is
(11:41):
rarely a positive change.
It typically means that thosegenes aren't getting expressed
properly or some other error ishappening and it can again cause
cells to be unstable or thingsjust not to signal the way that
they're supposed to.
And that is more common whenpeople have BMI is over 30, and
when people have BMI is under 30in general.
(12:03):
So that's just an Wow.
So that's a very large kind ofway that things work.
Another thing to think about isthat obesity in general, or
that weight being overespecially 30 BMI means that
your mitochondria aren't workingas well.
And guess what mitochondria are?
I remember it in anatomy, yes,yes, I think that's like the
(12:24):
only thing that people everremember from biology class, but
they're considered thepowerhouse of the cell, the
powerhouse, yes, yes.
The powerhouse of the cell.
Yes, they're very, veryimportant in how your cells deal
with energy and deal withnutrients coming in and how
those things are then processedfurther.
If they don't work very well,then you're creating a process
(12:45):
that leads to something calledoxidative stress, and oxidative
stress is basically you've gotthese molecules throughout your
body that are causing sometimesreactions in other molecules
that destabilize them, andsometimes those can be chain
reactions.
So not only one thing isgetting destabilized, but that's
causing things to spiral out ofcontrol in different processes.
(13:07):
So there is some evidenceactually that people over BMI's
authority have higher rates ofcancer earlier in their lives
and even more severe forms ofcancer or other disease, like
heart disease and lung disease,and Well, does cancer cells feed
off like weak cells, doesn't it?
(13:28):
Well, and sometimes this kindof dysfunction or this kind of
like, especially chain reactionof changes, can create an
environment in which cancercells can develop easier.
Okay, so it's a bit of likethink of you've got a train on a
track but now you're taking theguardrails off and so that
train can stay on the track, butif it derails, it'll go.
(13:48):
It's easier too.
It's easier for it to go flyinginto the neighborhood next door
as opposed to running into thatguardrail and being stopped
from causing even more damage.
So pretty interesting so far.
Speaker 1 (13:59):
It is.
Speaker 2 (14:00):
And then the other thought is that there's
basically a theory or a beliefand some and there's some data
around this that there's healthyfat and then there's fat that
can become not so healthy, andwhat this is called basically is
it's called a bunch of things,but adipose tissue is fat tissue
, and that adipose tissue canhave ways of being produced in
(14:22):
an unhealthy way or signaling inan unhealthy way too, to
contribute to things like theoxidative stress that then
destabilizes other molecules andcells potentially.
So all of it altogether.
Think of it like it's notdifferent parts, different
unrelated things.
This is all a web and alltogether.
Having a BMI of over 30 createsa state in your body where
(14:45):
things are not working as wellas they could, and oftentimes
that doesn't necessarily meanthat things are going to cause
disease or they're going to goway off the rails, but it means
that there's less protection forthings.
Yeah, because mutations likechanges are happening all the
time to us.
We live in an environment thathas lots of pollution in it,
lots of other factors that cancause these kinds of problems,
(15:07):
but when you take guardrails off, it just means that the
problems can get really worse,really bad and faster when
there's less protection, right?
Ok, so let's talk.
Does that kind of make sense sofar?
Speaker 1 (15:21):
It does.
Speaker 2 (15:21):
Yeah.
Speaker 1 (15:21):
Just my head.
I think deeply about thesethings.
Speaker 2 (15:25):
I love it.
Speaker 1 (15:26):
They talk about things.
Speaker 2 (15:27):
I love it.
And then, specifically, whenwe're talking about endocrine
function.
A lot of times we talk abouthormones and endocrine function
and what is that?
I would say that's even complexfor people who are in health
care, and so I'm going to try tobreak it down in a way that it
doesn't it's easy to think about, but this is really that
signaling and the pathways.
Endocrine and hormones arereally important themselves, but
(15:48):
they're even more important inhow they interact together and
what kind of impacts they haveon other signaling.
So think about steroids and I'mnot talking Well, I am talking
about the things that make youlike really big.
But in our own bodies, steroidhormones are things like
testosterone, for instance, orestrogen, and the way that our
body regulates these things isvery heavily impacted by what
(16:13):
genes we have, the epigenetics,which means how the genes get
expressed and used, and they areextremely sensitive to weight
and metabolism changes overall,which is why fertility is very
strongly impacted by weight atcertain, at that BMI of over 30,
and the same thing for sexualfunction.
(16:34):
It all makes sense yeah,starting to make sense and in
fact, the endocrine system isextremely heavily reliant on
lipid, meaning fat metabolism,and how we metabolize fat and
how that signals is extremelystrongly related to how our
hormones work.
And our hormones work a lotless good when we have a system
(16:57):
with fewer guardrails and withmore errors happening in it than
it does at BMI under 30, whenthose things are typically
working a little better.
Speaker 1 (17:05):
So that's potentially why I might be off the wall
saying this, but like PCOS, yeah.
Usually Obese, yeah, women.
Speaker 2 (17:15):
Yeah, absolutely so.
Pcos Polycystic OvarianSyndrome there's a lot of still
research into exactly how ithappens, but absolutely we know
that when estrogen andtestosterone and other hormones
are out of whack with each otherin women, it's really difficult
to have a baby because thosehormones have to be in really
good balance and there'sluteinizing hormone and
(17:36):
follicular stimulating himhormone and other hormones too
that play into this.
But unless those things are inreally good balance with each
other, it's really difficult tobe fertile and have a pregnancy
and even if you have a pregnancy, your rate of miscarriage and
things like that is higher ifthose things are not in balance
with each other.
Exactly when you have a BMIover 30, it's much more likely
(17:56):
for those things to be out ofbalance with each other and
therefore your ovaries may noteven be able to produce eggs or
may not be able to release themappropriately, and your chances
of having a viable pregnancy,even if you do, are lower.
So it all makes sense, yeah, sowhat happens when we actually
lower people's weights,especially in a sustainable way,
especially not in a crash tieat way, and we're actually
(18:19):
changing how these hormones aregetting regulated and how these
hormones are getting produced inappropriate levels with each
other, we're actually creatingthe sustainable changes that
allow people to be fertile, andeven on the men's side this
applies to, because sperm counts.
Libido, ability to haveerections and keep them, is all
(18:39):
very finely tuned as well.
Just like fertility is in women, fertility in men is very
similar.
So having the ability toactually have all these hormones
regulated appropriately witheach other under a BMI of 30 is
the reason that people have morefertility and better sexual
performance when people gothrough the process of weight
(18:59):
change and metabolic change withsurgery, right, yeah, so pretty
interesting, I think.
Speaker 1 (19:05):
Very much so is.
Speaker 2 (19:06):
Yeah, because it's like well, there's a reason for
everything, there's a reason,it's not magic.
Speaker 1 (19:10):
And we can't, or surgeons can't talk about these
things in a 15 minuteappointment?
Speaker 2 (19:15):
Not at all, and so that's the frustrating thing is
like I don't even think a lot ofmedical providers necessarily
know a ton about this and I willsay I know some about this and
I read a lot and I work on someof the research, but there's
still a lot we don't know and wedon't know all of the exact
mechanisms, like I wish it were,like a car engine that you're
like okay, well, there's thismany pistons and they work in
(19:35):
this specific way with physicsand it all works together this
way, because we know exactly allthe steps here.
We don't know all the steps.
We know approximately, we thinkwe know approximately how these
things are interacting witheach other and how these
different secondary impacts,that different hormones and
different molecules and allthese things are impacting each
(19:57):
other, but we don't know exactlyhow.
Speaker 1 (20:00):
So potentially, as time goes by, how those things
react can change.
So even if you're like, oh yeah, right on the ball.
Oh yeah, a month later, itcould be totally different.
Speaker 2 (20:09):
Exactly and that's also another reason that we've
talked about this a little bittoo when people go through
pregnancy or menopause or otherchanges.
That's why, anytime the systemchanges, you may experience
weight gain, you may experienceweight changes period, you may
experience things that now wehave an offset happening in one
side.
In order to balance things out,we kind of need an offset
somewhere else too.
(20:30):
So it's not superstraightforward, but we're
starting to understand like youcan't like a web, like you can't
touch one place and not have animpact throughout the whole
system, right?
So let's talk about sometargets actually for treating
weight.
We've definitely we know aboutGLP ones, which are like
Sixendom and Jarrow would go theozempic, all those things.
(20:51):
So GLP ones are GLP one.
Receptor agonists isspecifically what that class of
medication is, and it helps thebody be more sensitized to
insulin.
It helps the body processinsulin better so that you can
actually capture more of thebloodstream sugar and put it
into cells instead of keeping itin the bloodstream.
It has some other effects too,like slowing down the emptying
(21:14):
of the stomach and things likethat.
But that's actually a majorgenetic target technically for a
medication and that's very,very important.
All of the different thingsthat are involved in how we
process blood sugar are hugetargets for medications that
happen, that are useful foradults, but also even the one
that we talked about earlier,that in in civry, which is a
(21:36):
target for MCF receptor, is alsopart of that pathway too, so
pretty interesting.
There's other genes in thatpathway that are really
important, like leptin, leptinreceptor.
There's a bunch of others and,yeah, there's a lot of research
going on in terms of how wetarget these kinds of genes and
how they work with medications.
(21:57):
You've probably also heard ofCRISPR.
Maybe you've heard of it, maybenot, I don't know.
Speaker 1 (22:05):
I don't think so.
Speaker 2 (22:06):
Okay, so CRISPR is a form of gene editing and it
specifically stands forclustered, regularly interspaced
, short palindromic repeats forliving organism gene editing,
yeah, and so that's a reallylong term, I know, I know.
But the idea of basically beingin human beings like you and me
(22:29):
, or in living organisms, youcan actually go in and target
very specifically littlesections of genes that we want
to change for whatever reason,and you can actually go in and
change them and have an impact.
That right now there's CRISPRtechnology that's FDA approved,
I believe, for sickle celldisease, but there are targets
(22:50):
in fact over 60 of them thatpotentially could be used in the
treatment of obesity.
Okay, yeah, so like even geneediting in living people could
be, down the road, a target,right, yeah.
So literally going in, snippingout the part that doesn't, that
we don't want, and putting insomething we do, could be a
target for helping people loseweight in the future.
(23:11):
Now, science is crazy, scienceis crazy.
But we talked about the onethat already exists on the
market, the Msevri and Sivri.
I'm so sorry, I'm somispronouncing that one, but
that's the one that's on themarket.
Now Other targets we talkedabout even in another episode,
things like fecal transplants,for instance.
That target, yeah, that targetthe microbiome.
You totally predicted all ofthis, tammy.
(23:32):
I love that you're so curious.
Yes, you're so curious I am.
It's great.
But the microbiome, so all ofthe bacteria and more, not just
bacteria but viruses and thingsthat live in our bodies,
alongside us and sometimes arehelpful to us, sometimes are
harmful to us.
And again, it's all aboutbalance, right?
So it's not that bacteria isbad or good, it's that the
(23:52):
balance of what kind of bacteriawe've got in our bodies is bad
or good.
There's a lot of looking into.
Can we target specificallyobesity with essentially what's
going on in the gut of a personwho has healthy weight and the
gut of a person who has not sohealthy weight and is having
impacts from that?
Can we bring the healthy stuffinto the less than healthy body
(24:15):
and make a difference even inthe microbiome, even in the
bacteria that's happening in it?
So that's one thing, and thenthere's even some potential for
targeting how genes arecontrolled.
And how genes are controlled,if you think about it, is
actually something we do a lot.
When you're growing fruits orvegetables, you grow them in a
(24:36):
specific like.
You can grow them in a hothouse, right, like, even if
you're in the middle of thewinter in Iowa in a blizzard,
but you have a beautiful rightnow, right, but you have a
beautiful hot house, you havegreat lamps, you have warm,
moist environment, you havegreat soil all that stuff.
You can grow tomatoes in themiddle of a blizzard, right.
So if you think about it, youcan also put people into
(24:56):
environments that either help orharm how their bodies express
certain genes, right, and thatis impacted by the food we eat,
by how much sleep we get, by howmuch stress we have, by all the
things that we've talked aboutin other episodes.
All of these lifestyle factors,how we move our bodies those
lifestyle factors are having animpact in how we express our
(25:19):
genes on a daily basis.
Crazy, yes, and so some, yes,some of the treatment here, some
of the ways that we actuallydeal with this.
When we talk about diet andexercise as lifestyle, we're not
really just talking about like,ooh, it's nice to eat healthier
, ooh, it's nice to move yourbody.
It's quite literally having animpact on how you are expressing
your genes every day, and thatactually should be encouraging
(25:41):
to people, because these arethings that are not set in stone
.
When you do physical activitytoday differently than you did
yesterday, or when you make achoice to eat differently now
than you did this morning, yourbody is constantly updating
based on what you're doing.
Now there is some evidence that, yes, there's memory, and of
course, it's not like you run amarathon and all of a sudden you
(26:02):
know you weigh 50 pounds less.
That's not how it works, butthe way that you're actually
expressing your genes absolutelydoes get updated on essentially
a minute to minute basis.
Isn't that fascinating?
Speaker 1 (26:16):
It very much so is.
Speaker 2 (26:17):
Right.
So the impact that you can haveon your body by making a
different choice, through evenlifestyle changes like diet or
exercise, your body responds tothat immediately.
It might take a little bit morethan immediately to start to
see results, but do notunderestimate the impact that
those things are having on yourbody immediately.
So cheat meals, not going tokill at all, it's not going to
(26:39):
kill at all, and that's backedby science.
That is backed by science.
Some other things to thinkabout, you know, and that's
super interesting to me, becausewe can't go in and, like, edit
people's genes right now.
We can't go in and like, tammy,I'm going to, you know, find
this and then fix it for you.
And even if we could, thatwould probably cost hundreds of
thousands of dollars at thispoint It'd be super expensive.
But guess what?
We can have an impact on howmuch we're sleeping and we can
(27:03):
have an impact on what kinds offoods we're choosing to eat and
when.
A little bit more.
I wouldn't say like we'reperfect on that.
We can't totally change ourenvironment, but it's to say
that environmental change can bereally, really important.
There's also some studies thatgo into looking into like
probiotics and how else we canchange our gut bacteria, gut
health, and we don't have a tonof evidence there or ton of
(27:26):
research there, but in thefuture I think that's going to
be a really big target ofunderstanding how to help people
manage their weight too.
Speaker 1 (27:33):
Yeah, I think gut bacteria has a lot to do with it
.
Speaker 2 (27:37):
Oh yeah, absolutely.
Speaker 1 (27:38):
And that's what I'm learning.
Speaker 2 (27:39):
Oh yes, and it also changes over time.
Another kind of the maintakeaways from this is one very
little of set in stone Becauseyou have a certain gene or just
because you have a certainsyndrome, that really is only
making an impact, that set instone for less than 1% of people
and then for the rest of us,99%.
It's the combination of things.
(28:00):
It's a combination of lifestyleand our genes and how those
genes are getting expressed on aday to day basis, and I think
what also is interesting is thatall of these things are related
to each other.
Yeah, you have enough thingsthat push you one way and it's
very difficult to not gainweight and not have weight.
That then becomes really,really difficult to lose over
(28:21):
time, and for some folks they'regenetically lucky.
Okay, that happens, so telling.
I think also having thisunderstanding that, like people
are totally responsible or toblame for whatever weight they
have, is kind of ludicrous,because obviously not.
There's a lot of impacts wecan't control, and the ones that
we can have some impact andthey can even have an impact the
(28:42):
second you start doing themit's kind of interesting too.
So those are my takeaways.
There's a lot of targets here.
There's a lot of things wedon't know.
There's things that we'restarting to understand.
In the show notes for this, I'mgoing to put in a lot of links
and a lot more details.
For those folks who want todive into the genetics in more
of obesity and weight and,believe me, this is absolutely
just scratching the surface ofwhat's out there Absolutely.
(29:04):
I wanted this to not be themost boring section like lesson
we ever have, or was boringpodcast we ever have.
Speaker 1 (29:11):
No, I think the people that understand that a
calorie is not calorie my runson my hand want to know why, and
this is why why.
Speaker 2 (29:22):
This is why Because ultimately, even though we all
have the same kinds of pathwaysin our body, how those pathways
get used and how those pathwaysget expressed are extremely
unique.
They are extremely individual.
Speaker 1 (29:35):
I feel like you can compare that to.
You know, we all live in theworld.
Let's say we all live in Iowa.
We all have the same resources,but we all live very different
lives.
Our body is choosing to go downthis rope.
Sometimes we can't control it.
Right and there's things, butif we figure out how we can,
Exactly, exactly.
Speaker 2 (29:54):
And there's things we can control, there's things we
can't.
So absolutely figuring out howto leverage the ones that we can
control and then the ones thatwe can't, well, screw it, we
can't control it anyway.
So let's not blame people forthe things we can't control, but
actually focus on the stuff wecan.
And that's where, absolutelyyeah, and that's exactly where
some of these treatments likemedications and things like that
(30:15):
, have a role.
But even I think this is themost fascinating thing surgery,
like a surgical procedure thatwe do on people, has an impact
on how their genes are expresseddown the road.
Speaker 1 (30:26):
Yeah, that is the crazy part.
Speaker 2 (30:28):
Isn't that crazy.
And it's so cool because Ithink everyone who goes through
this process sees that in actionand this is a little bit of
that under the hood, why ithappens.
Speaker 1 (30:36):
Right, absolutely.
Speaker 2 (30:38):
Yeah.
Speaker 1 (30:39):
Well, thank you, for I know you're like going to that
was a lot, but no, for thepeople that really are trying to
figure out why.
Yeah, and that I talked in theprevious episode about your old
dad was at the gym and gotjudged for having bariatric
surgery.
She could listen and be likeman.
This is this is why, yeah, Shutyour mouth.
Speaker 2 (31:02):
Yeah, shut your mouth because, like, your body is
basically becoming a laboratory,you're turning your body into a
factory for changing and forbecoming healthier and for
converting what things have madeit challenging for you and for
your body to be where you wantit to be and making those things
work better.
And I think people should becongratulated for converting
their body into a laboratoryhonestly and allowing those
(31:25):
changes to happen.
I think it's really cool?
Speaker 1 (31:26):
Yeah, absolutely.
Thank you for the sciencelesson.
Speaker 2 (31:29):
Oh, you're so welcome .
I promise not to do too many ofthese.
Speaker 1 (31:31):
I promise Because, yes, I definitely want to know
why we are the way we are.
People that are obese don'twant to be obese.
Speaker 2 (31:38):
Well, and the thing is, obesity isn't something to
want or not want or somethinglike that.
Really, even I think it'sweight is complicated, as we are
learning, and for some people,even if they do the exact same
thing that somebody else does,their body is going to interpret
it very differently and carryit out very differently and
they're going to have a verydifferent weight as a result.
(31:59):
And it is, I think, true thatwhen people have a BMI over 30,
if they're not, likeprofessional athletes or
otherwise, super heavy withmuscle mass and things like that
, there are things that arehappening in bodies that make it
more difficult to avoid certainkinds of metabolism diseases
(32:20):
and then make it easier forpeople who have BMI under 30 to
have more healthy cells and havemore healthy gene expression
and things like that.
But to say that it applies toeveryone across the board is not
correct, and certainly to saythat it's anyone's fault that
their bodies are doing that iscompletely bogus, absolutely so,
if nothing else, I hope that'sthe takeaway that hey, guess
(32:41):
what?
We've got some things that wecan do about it with medications
and surgery and lifestyle, andthat we're constantly developing
more, because this is a growingfield in every possible way,
and I'm thankful for it, becausethe more we know, the better we
can all do.
Speaker 1 (32:55):
Absolutely Thank you for all of that, because I know
it took a while to figure outexactly how you were going to
explain it to people that mayhave no medical or science
background.
So thank you for making that.
Speaker 2 (33:08):
I hope that wasn't totally gobbledygook for
everyone.
No, no.
Speaker 1 (33:12):
And for those that don't want to go that deep, they
don't have to.
Speaker 2 (33:15):
Not at all.
They can skip an episode, skipthis episode and just go.
No, thank you, that is right.
Speaker 1 (33:20):
Well, thank you all for listening and we will be
back again.
Thank you.
Speaker 2 (33:24):
Yeah, thank you.
Speaker 1 (33:25):
Bye.
Welcome to Core Bariatric's podcast, hosted by
bariatric surgeon Dr MariaIliakova and Tami LaCoste,
bariatric coordinator and apatient herself.
Our goal is building andelevating our community.
The Core Bariatric podcast doesnot offer medical advice,
diagnosis or treatment.
On this podcast, we aim toshare stories, support and
(00:22):
insight into the world beyondthe clinic.
Let's get into it, maria.
It's all.
Eat less, move more.
Right, that's it, that's all100%.
Speaker 2 (00:32):
Yes, it is all that.
Yes, 100%, tami.
Okay, why wouldn't you even ask?
Of course, ins and outs, hello.
Speaker 1 (00:42):
Because that's what everybody thinks.
Speaker 2 (00:44):
That is what everybody thinks and everybody's
wrong, anyway.
So no, but you're actuallyright.
So today we're going to bediving into genetics and weight
genetics and obesity.
And the reason why is becauseguess what, if it were simple,
everybody would not be asking us, not be wondering about this
and not be struggling with this,because we'd have it all
(01:05):
figured out.
If an after-waste killer in amile run was a mile run, we'd
all be the same size, exactly.
So I am always really curiousabout the why and the behind the
scenes, and I think you are too.
So I wanted to create a podcastepisode that was all about
genetics and obesity, and thereason why is because I actually
have a background in molecularbiology, genetics, studying
(01:27):
proteins, all that fun stuff.
What.
So I love this.
It is so exciting and I thinkyou're going to find that.
Speaker 1 (01:33):
Look, I've known you for how long and I did not know
that.
Speaker 2 (01:36):
Yeah, and so I am really jazzed about this.
Speaker 1 (01:39):
And you're 34.
Speaker 2 (01:41):
Well, you know, sometimes we do, sometimes
people have good childhoods andsometimes they have.
Speaker 1 (01:46):
actually I don't really get childhood, but I mean
I got three kids and I'm 30 andyou, just you have degrees and
you're 34.
Speaker 2 (01:54):
Yeah, so instead of having kids, I had degrees, and
so yes, anyway, but I am reallyreally jazzed about genetics and
about all of the ways that ourbodies actually regulate how
things work, and how thatchanges over time and how it
relates to weight is pretty, Ithink, fascinating.
So you're going to go on alittle bit of a journey with me
today.
Yes, please.
Hopefully we will not bore thepants off of everyone listening
(02:16):
today.
Speaker 1 (02:17):
I want to add that, so we're doing video.
Yes, maria is all dressed up ina minnowsuit shirt.
Speaker 2 (02:22):
Oh please, I'm just like a t-shirt.
I'm in a t-shirt, I'm in at-shirt.
Speaker 1 (02:26):
Well, red is your color.
Well, thank you Anyway genetics, yes, genetics.
Speaker 2 (02:29):
So anyway, let's talk real quick about weight and
metabolic change.
We have talked a lot about inother episodes the fact that
surgery and other ways thatpeople can lose weight can have
impacts on your signaling andimpacts on your metabolism, and
today we're going to talk intothe weeds a bit more about what
that means.
On a cell level, and evensmaller than the cell, is the
(02:51):
genes, and we're not talkingabout, like Levi's genes or gas
genes.
We're talking about the genesthat get expressed and create
all the different parts of yourbody, all the different cells
and all the different proteinsand all that.
But what do you Into the thickof it?
Into the thick of it, tammy,what do you know so far about
genes and weight, or genes andobesity?
Speaker 1 (03:13):
I know that most people that are obese their kids
are obese, their parents areobese there has to be a
connection there.
I love that.
Speaker 2 (03:25):
And, honestly, a lot of what we know about genetics
comes from those observations ofpeople going wait a second.
There's got to be some kind oflink here, because this runs in
families.
And actually I remember I hadone patient that was pretty
funny and I said what runs inyour family?
And they said nobody runs in myfamily and we laughed and we
had a great time, but anyway,but you're obviously right,
(03:45):
these things do run in familiesand, however do we do genetic
testing on a regular basis forour patients.
No no, we do not.
Speaker 1 (03:54):
I don't think anybody really does right, Because
genetic testing isn't covered byinsurance.
Speaker 2 (03:59):
Well, there's that.
We run into our age old themeof it's not covered by insurance
, yes, but here there's also abasis for that, because a lot of
weight isn't just genetics andisn't just known genetics,
meaning like we know exactlywhat gene is being affected, and
that's why people have weightstruggles or weight challenges
more than other people.
(04:19):
It's a lot more factors thanjust that and we're going to
talk about today some targets oftreatment, how things work on
the sort of gene and cell level,and basically what kind of
treatments exist now, and it's alittle bit about in the future
where things are going to.
So that's kind of how we'regoing to structure today.
So, yeah, there is actually onemedication on the market called
(04:43):
in Crevy or in Crevy, dependingon how you pronounce it, and
Sivri, I think some people sayto and it specifically targets
one gene that gets expressed andcan cause overeating or the
desire to overeat, and can causeobesity in some people.
Right, and I think we'veactually seen some of the reps
for that medication in our ownoffice before.
(05:05):
Yeah, the light bulb went off.
Sorry, that's right.
No, no, that's totally fine,and there is genetic testing
that can be done that theircompany actually covers at this
point for patients, yes.
However, that affects way lessthan 1% of people who have
excess weight or obesity, soit's not common, and that's kind
of the theme behind a lot ofthese things.
(05:26):
Let me just run through a listof a couple of things that can
be related to excess weight thatare genetic syndromes, and
those are things likemelanocortin for receptor
deficiency, which is what thatmedication targets, leptin
deficiency, leptin receptordeficiency, brain-derived
metropic factor deficiency andprohormone convertase 1
(05:47):
deficiency, cohen syndrome,bartopetal syndrome, beckwith
Wiedemann syndrome, and there'smore.
I won't go through all of them,but there's over a dozen
different syndromes and specificgenes that are thought to be
directly related to obesity.
All together, all of thosethings, all the more than dozen
(06:08):
of those syndromes and specificmutations still account for less
than 1% of obesity.
So it's still 99% of the time.
There's still way more factorsthan just genetics involved.
So one big takeaway is, yes, itcan be genetics, but oftentimes
it's not just genetics, but westill need to look at it Exactly
(06:31):
.
So I think if you're havingsomeone who isn't, for instance,
like from a healthcareperspective, if you have someone
who is trying everything,including surgery, they're still
not losing weight.
They're trying medications,they're still not losing weight.
Or you have a kid, for instance, under the age of 16, who's
having a lot of issues withweight, even though their diet
and exercise is well-controlled.
They don't have really haveother medical conditions.
(06:52):
Really really important toconsider some of these syndromes
and genetic considerations.
So things to think about.
So when we're talking aboutadults, yeah, these things are
pretty rare.
Speaker 1 (07:03):
So I'm just thinking about someone in our family.
The mom and dad are not big.
The man is very big and notlike he's very active, he's on a
paving crew, it's a very active, he's just big guy, and his son
, who is only 12, baseball, allthe things very big.
(07:24):
But how did we get from two notso big people, sure, to a son
who is very large and then agrandson that is very large?
It just makes me think.
Speaker 2 (07:35):
Absolutely.
That's a good way to thinkabout it, because sometimes, if
it is genetics that is playing arole, those don't necessarily
get expressed in everygeneration.
So, if you think about it, yeah, you don't have to look further
.
Yeah, if you think about it,you can actually like dwarfism,
for instance, being a dwarf andI hope I am not saying anything
that is offending anyone.
This is just sort of somethingpeople are aware of.
(07:56):
You can actually havecompletely regular adult-sized
parents and have a dwarf child,or vice versa, you can have a
dwarf parent and still have aregular-sized child from, yeah,
depending on who they mate with.
So not all genes, even ifinherited, and gene mutations,
(08:18):
are expressed and not everythingis just straight heredity Like
your parents have this andtherefore you have this and
therefore your kids will havethis.
It also depends on who yourpartner is when you have a child
and it depends on what theirgenetics are and it depends on
what's dominant and what'srecessive, what gets expressed
more than other things, and whatgets masked by having a
(08:38):
dominant gene that getsexpressed instead.
So, for fear of getting toointo the weeds on this one,
suffice it to say that there's alot of different targets, in
fact, over 60 different genesthat are thought to have an
impact on people's weight andmetabolism, and they control a
lot of the same pathways that weactually target with
(08:59):
medications and with surgery.
So, interestingly enough, wewere talking in another episode
about how surgery works and wewere talking about like PI3K
pathways and leptin and ghrelinand GLP1s and things like that.
And guess what?
Those are the same kind oftargets, that the same kinds of
genes and the same kinds ofpathways that affect weight to
(09:19):
begin with.
So the very things that we'retargeting with medications and
surgery or other approaches arealso things that contribute to
what someone weighs.
Speaker 1 (09:28):
All right, it all comes together.
Speaker 2 (09:30):
It all comes together eventually, and there are a
couple of things that are prettyinteresting just as a global,
so big picture here.
When people have extra weight,especially weight over a BMI of
30, typically you can actuallycause the cells to behave
differently than they wouldotherwise.
So some stem cells are not asstrong, essentially, as others
(09:55):
in this situation, and so theydon't different, they don't
become as many cells as well asthey do in people who have BMI
under 30, for instance, and whatthat leads to is think of it
this way you have a pool of goo,and that goo can become brain
cells, it can become heart cells, it can become muscle cells, it
can become bone cells or jointcells or something like that.
(10:17):
When your weight, when your BMI, is over 30, the ability for
those cells to become healthy,adult cells that are these
different kinds is less.
So even the ability to heal andespecially when you're
recovering from injury, traumasurgery, those kinds of things
is less good at higher weightsthan it is at lower weights on
(10:38):
average.
So that's, I think, kind ofinteresting and that's
absolutely yeah it very much sois.
And that's impacted by genetics, but it's also impacted by how
those genes are gettingexpressed, and we'll get into
something called epigenetics,which is one level above
genetics.
So not even what genes you have, but how they're actually
getting used in the real bodyand how they're, whether they're
(10:59):
showing up or whether they'rebeing masked, is something that
happens on a day to day basis,on a minute to minute, second to
second basis, in all of ourbodies at all time.
Very interesting stuff?
No, it is.
It is so, moving on from there,there's also something called
genomic instability, and that'snot like being psycho or
unstable or a little different.
(11:19):
I got that.
Oh well, we all got that, so Iget it.
But genomic instability isbasically when genes are in an
environment to stay what theyare without any further changes
and they can be then used to beexpressed in a certain way
without changes.
When there's instability, itmeans that the genes that you
have even can be changedactively, and that change is
(11:41):
rarely a positive change.
It typically means that thosegenes aren't getting expressed
properly or some other error ishappening and it can again cause
cells to be unstable or thingsjust not to signal the way that
they're supposed to.
And that is more common whenpeople have BMI is over 30, and
when people have BMI is under 30in general.
(12:03):
So that's just an Wow.
So that's a very large kind ofway that things work.
Another thing to think about isthat obesity in general, or
that weight being overespecially 30 BMI means that
your mitochondria aren't workingas well.
And guess what mitochondria are?
I remember it in anatomy, yes,yes, I think that's like the
(12:24):
only thing that people everremember from biology class, but
they're considered thepowerhouse of the cell, the
powerhouse, yes, yes.
The powerhouse of the cell.
Yes, they're very, veryimportant in how your cells deal
with energy and deal withnutrients coming in and how
those things are then processedfurther.
If they don't work very well,then you're creating a process
(12:45):
that leads to something calledoxidative stress, and oxidative
stress is basically you've gotthese molecules throughout your
body that are causing sometimesreactions in other molecules
that destabilize them, andsometimes those can be chain
reactions.
So not only one thing isgetting destabilized, but that's
causing things to spiral out ofcontrol in different processes.
(13:07):
So there is some evidenceactually that people over BMI's
authority have higher rates ofcancer earlier in their lives
and even more severe forms ofcancer or other disease, like
heart disease and lung disease,and Well, does cancer cells feed
off like weak cells, doesn't it?
(13:28):
Well, and sometimes this kindof dysfunction or this kind of
like, especially chain reactionof changes, can create an
environment in which cancercells can develop easier.
Okay, so it's a bit of likethink of you've got a train on a
track but now you're taking theguardrails off and so that
train can stay on the track, butif it derails, it'll go.
(13:48):
It's easier too.
It's easier for it to go flyinginto the neighborhood next door
as opposed to running into thatguardrail and being stopped
from causing even more damage.
So pretty interesting so far.
Speaker 1 (13:59):
It is.
Speaker 2 (14:00):
And then the other thought is that there's
basically a theory or a beliefand some and there's some data
around this that there's healthyfat and then there's fat that
can become not so healthy, andwhat this is called basically is
it's called a bunch of things,but adipose tissue is fat tissue
, and that adipose tissue canhave ways of being produced in
(14:22):
an unhealthy way or signaling inan unhealthy way too, to
contribute to things like theoxidative stress that then
destabilizes other molecules andcells potentially.
So all of it altogether.
Think of it like it's notdifferent parts, different
unrelated things.
This is all a web and alltogether.
Having a BMI of over 30 createsa state in your body where
(14:45):
things are not working as wellas they could, and oftentimes
that doesn't necessarily meanthat things are going to cause
disease or they're going to goway off the rails, but it means
that there's less protection forthings.
Yeah, because mutations likechanges are happening all the
time to us.
We live in an environment thathas lots of pollution in it,
lots of other factors that cancause these kinds of problems,
(15:07):
but when you take guardrails off, it just means that the
problems can get really worse,really bad and faster when
there's less protection, right?
Ok, so let's talk.
Does that kind of make sense sofar?
Speaker 1 (15:21):
It does.
Speaker 2 (15:21):
Yeah.
Speaker 1 (15:21):
Just my head.
I think deeply about thesethings.
Speaker 2 (15:25):
I love it.
Speaker 1 (15:26):
They talk about things.
Speaker 2 (15:27):
I love it.
And then, specifically, whenwe're talking about endocrine
function.
A lot of times we talk abouthormones and endocrine function
and what is that?
I would say that's even complexfor people who are in health
care, and so I'm going to try tobreak it down in a way that it
doesn't it's easy to think about, but this is really that
signaling and the pathways.
Endocrine and hormones arereally important themselves, but
(15:48):
they're even more important inhow they interact together and
what kind of impacts they haveon other signaling.
So think about steroids and I'mnot talking Well, I am talking
about the things that make youlike really big.
But in our own bodies, steroidhormones are things like
testosterone, for instance, orestrogen, and the way that our
body regulates these things isvery heavily impacted by what
(16:13):
genes we have, the epigenetics,which means how the genes get
expressed and used, and they areextremely sensitive to weight
and metabolism changes overall,which is why fertility is very
strongly impacted by weight atcertain, at that BMI of over 30,
and the same thing for sexualfunction.
(16:34):
It all makes sense yeah,starting to make sense and in
fact, the endocrine system isextremely heavily reliant on
lipid, meaning fat metabolism,and how we metabolize fat and
how that signals is extremelystrongly related to how our
hormones work.
And our hormones work a lotless good when we have a system
(16:57):
with fewer guardrails and withmore errors happening in it than
it does at BMI under 30, whenthose things are typically
working a little better.
Speaker 1 (17:05):
So that's potentially why I might be off the wall
saying this, but like PCOS, yeah.
Usually Obese, yeah, women.
Speaker 2 (17:15):
Yeah, absolutely so.
Pcos Polycystic OvarianSyndrome there's a lot of still
research into exactly how ithappens, but absolutely we know
that when estrogen andtestosterone and other hormones
are out of whack with each otherin women, it's really difficult
to have a baby because thosehormones have to be in really
good balance and there'sluteinizing hormone and
(17:36):
follicular stimulating himhormone and other hormones too
that play into this.
But unless those things are inreally good balance with each
other, it's really difficult tobe fertile and have a pregnancy
and even if you have a pregnancy, your rate of miscarriage and
things like that is higher ifthose things are not in balance
with each other.
Exactly when you have a BMIover 30, it's much more likely
(17:56):
for those things to be out ofbalance with each other and
therefore your ovaries may noteven be able to produce eggs or
may not be able to release themappropriately, and your chances
of having a viable pregnancy,even if you do, are lower.
So it all makes sense, yeah, sowhat happens when we actually
lower people's weights,especially in a sustainable way,
especially not in a crash tieat way, and we're actually
(18:19):
changing how these hormones aregetting regulated and how these
hormones are getting produced inappropriate levels with each
other, we're actually creatingthe sustainable changes that
allow people to be fertile, andeven on the men's side this
applies to, because sperm counts.
Libido, ability to haveerections and keep them, is all
(18:39):
very finely tuned as well.
Just like fertility is in women, fertility in men is very
similar.
So having the ability toactually have all these hormones
regulated appropriately witheach other under a BMI of 30 is
the reason that people have morefertility and better sexual
performance when people gothrough the process of weight
(18:59):
change and metabolic change withsurgery, right, yeah, so pretty
interesting, I think.
Speaker 1 (19:05):
Very much so is.
Speaker 2 (19:06):
Yeah, because it's like well, there's a reason for
everything, there's a reason,it's not magic.
Speaker 1 (19:10):
And we can't, or surgeons can't talk about these
things in a 15 minuteappointment?
Speaker 2 (19:15):
Not at all, and so that's the frustrating thing is
like I don't even think a lot ofmedical providers necessarily
know a ton about this and I willsay I know some about this and
I read a lot and I work on someof the research, but there's
still a lot we don't know and wedon't know all of the exact
mechanisms, like I wish it were,like a car engine that you're
like okay, well, there's thismany pistons and they work in
(19:35):
this specific way with physicsand it all works together this
way, because we know exactly allthe steps here.
We don't know all the steps.
We know approximately, we thinkwe know approximately how these
things are interacting witheach other and how these
different secondary impacts,that different hormones and
different molecules and allthese things are impacting each
(19:57):
other, but we don't know exactlyhow.
Speaker 1 (20:00):
So potentially, as time goes by, how those things
react can change.
So even if you're like, oh yeah, right on the ball.
Oh yeah, a month later, itcould be totally different.
Speaker 2 (20:09):
Exactly and that's also another reason that we've
talked about this a little bittoo when people go through
pregnancy or menopause or otherchanges.
That's why, anytime the systemchanges, you may experience
weight gain, you may experienceweight changes period, you may
experience things that now wehave an offset happening in one
side.
In order to balance things out,we kind of need an offset
somewhere else too.
(20:30):
So it's not superstraightforward, but we're
starting to understand like youcan't like a web, like you can't
touch one place and not have animpact throughout the whole
system, right?
So let's talk about sometargets actually for treating
weight.
We've definitely we know aboutGLP ones, which are like
Sixendom and Jarrow would go theozempic, all those things.
(20:51):
So GLP ones are GLP one.
Receptor agonists isspecifically what that class of
medication is, and it helps thebody be more sensitized to
insulin.
It helps the body processinsulin better so that you can
actually capture more of thebloodstream sugar and put it
into cells instead of keeping itin the bloodstream.
It has some other effects too,like slowing down the emptying
(21:14):
of the stomach and things likethat.
But that's actually a majorgenetic target technically for a
medication and that's very,very important.
All of the different thingsthat are involved in how we
process blood sugar are hugetargets for medications that
happen, that are useful foradults, but also even the one
that we talked about earlier,that in in civry, which is a
(21:36):
target for MCF receptor, is alsopart of that pathway too, so
pretty interesting.
There's other genes in thatpathway that are really
important, like leptin, leptinreceptor.
There's a bunch of others and,yeah, there's a lot of research
going on in terms of how wetarget these kinds of genes and
how they work with medications.
(21:57):
You've probably also heard ofCRISPR.
Maybe you've heard of it, maybenot, I don't know.
Speaker 1 (22:05):
I don't think so.
Speaker 2 (22:06):
Okay, so CRISPR is a form of gene editing and it
specifically stands forclustered, regularly interspaced
, short palindromic repeats forliving organism gene editing,
yeah, and so that's a reallylong term, I know, I know.
But the idea of basically beingin human beings like you and me
(22:29):
, or in living organisms, youcan actually go in and target
very specifically littlesections of genes that we want
to change for whatever reason,and you can actually go in and
change them and have an impact.
That right now there's CRISPRtechnology that's FDA approved,
I believe, for sickle celldisease, but there are targets
(22:50):
in fact over 60 of them thatpotentially could be used in the
treatment of obesity.
Okay, yeah, so like even geneediting in living people could
be, down the road, a target,right, yeah.
So literally going in, snippingout the part that doesn't, that
we don't want, and putting insomething we do, could be a
target for helping people loseweight in the future.
(23:11):
Now, science is crazy, scienceis crazy.
But we talked about the onethat already exists on the
market, the Msevri and Sivri.
I'm so sorry, I'm somispronouncing that one, but
that's the one that's on themarket.
Now Other targets we talkedabout even in another episode,
things like fecal transplants,for instance.
That target, yeah, that targetthe microbiome.
You totally predicted all ofthis, tammy.
(23:32):
I love that you're so curious.
Yes, you're so curious I am.
It's great.
But the microbiome, so all ofthe bacteria and more, not just
bacteria but viruses and thingsthat live in our bodies,
alongside us and sometimes arehelpful to us, sometimes are
harmful to us.
And again, it's all aboutbalance, right?
So it's not that bacteria isbad or good, it's that the
(23:52):
balance of what kind of bacteriawe've got in our bodies is bad
or good.
There's a lot of looking into.
Can we target specificallyobesity with essentially what's
going on in the gut of a personwho has healthy weight and the
gut of a person who has not sohealthy weight and is having
impacts from that?
Can we bring the healthy stuffinto the less than healthy body
(24:15):
and make a difference even inthe microbiome, even in the
bacteria that's happening in it?
So that's one thing, and thenthere's even some potential for
targeting how genes arecontrolled.
And how genes are controlled,if you think about it, is
actually something we do a lot.
When you're growing fruits orvegetables, you grow them in a
(24:36):
specific like.
You can grow them in a hothouse, right, like, even if
you're in the middle of thewinter in Iowa in a blizzard,
but you have a beautiful rightnow, right, but you have a
beautiful hot house, you havegreat lamps, you have warm,
moist environment, you havegreat soil all that stuff.
You can grow tomatoes in themiddle of a blizzard, right.
So if you think about it, youcan also put people into
(24:56):
environments that either help orharm how their bodies express
certain genes, right, and thatis impacted by the food we eat,
by how much sleep we get, by howmuch stress we have, by all the
things that we've talked aboutin other episodes.
All of these lifestyle factors,how we move our bodies those
lifestyle factors are having animpact in how we express our
(25:19):
genes on a daily basis.
Crazy, yes, and so some, yes,some of the treatment here, some
of the ways that we actuallydeal with this.
When we talk about diet andexercise as lifestyle, we're not
really just talking about like,ooh, it's nice to eat healthier
, ooh, it's nice to move yourbody.
It's quite literally having animpact on how you are expressing
your genes every day, and thatactually should be encouraging
(25:41):
to people, because these arethings that are not set in stone
.
When you do physical activitytoday differently than you did
yesterday, or when you make achoice to eat differently now
than you did this morning, yourbody is constantly updating
based on what you're doing.
Now there is some evidence that, yes, there's memory, and of
course, it's not like you run amarathon and all of a sudden you
(26:02):
know you weigh 50 pounds less.
That's not how it works, butthe way that you're actually
expressing your genes absolutelydoes get updated on essentially
a minute to minute basis.
Isn't that fascinating?
Speaker 1 (26:16):
It very much so is.
Speaker 2 (26:17):
Right.
So the impact that you can haveon your body by making a
different choice, through evenlifestyle changes like diet or
exercise, your body responds tothat immediately.
It might take a little bit morethan immediately to start to
see results, but do notunderestimate the impact that
those things are having on yourbody immediately.
So cheat meals, not going tokill at all, it's not going to
(26:39):
kill at all, and that's backedby science.
That is backed by science.
Some other things to thinkabout, you know, and that's
super interesting to me, becausewe can't go in and, like, edit
people's genes right now.
We can't go in and like, tammy,I'm going to, you know, find
this and then fix it for you.
And even if we could, thatwould probably cost hundreds of
thousands of dollars at thispoint It'd be super expensive.
But guess what?
We can have an impact on howmuch we're sleeping and we can
(27:03):
have an impact on what kinds offoods we're choosing to eat and
when.
A little bit more.
I wouldn't say like we'reperfect on that.
We can't totally change ourenvironment, but it's to say
that environmental change can bereally, really important.
There's also some studies thatgo into looking into like
probiotics and how else we canchange our gut bacteria, gut
health, and we don't have a tonof evidence there or ton of
(27:26):
research there, but in thefuture I think that's going to
be a really big target ofunderstanding how to help people
manage their weight too.
Speaker 1 (27:33):
Yeah, I think gut bacteria has a lot to do with it
.
Speaker 2 (27:37):
Oh yeah, absolutely.
Speaker 1 (27:38):
And that's what I'm learning.
Speaker 2 (27:39):
Oh yes, and it also changes over time.
Another kind of the maintakeaways from this is one very
little of set in stone Becauseyou have a certain gene or just
because you have a certainsyndrome, that really is only
making an impact, that set instone for less than 1% of people
and then for the rest of us,99%.
It's the combination of things.
(28:00):
It's a combination of lifestyleand our genes and how those
genes are getting expressed on aday to day basis, and I think
what also is interesting is thatall of these things are related
to each other.
Yeah, you have enough thingsthat push you one way and it's
very difficult to not gainweight and not have weight.
That then becomes really,really difficult to lose over
(28:21):
time, and for some folks they'regenetically lucky.
Okay, that happens, so telling.
I think also having thisunderstanding that, like people
are totally responsible or toblame for whatever weight they
have, is kind of ludicrous,because obviously not.
There's a lot of impacts wecan't control, and the ones that
we can have some impact andthey can even have an impact the
(28:42):
second you start doing themit's kind of interesting too.
So those are my takeaways.
There's a lot of targets here.
There's a lot of things wedon't know.
There's things that we'restarting to understand.
In the show notes for this, I'mgoing to put in a lot of links
and a lot more details.
For those folks who want todive into the genetics in more
of obesity and weight and,believe me, this is absolutely
just scratching the surface ofwhat's out there Absolutely.
(29:04):
I wanted this to not be themost boring section like lesson
we ever have, or was boringpodcast we ever have.
Speaker 1 (29:11):
No, I think the people that understand that a
calorie is not calorie my runson my hand want to know why, and
this is why why.
Speaker 2 (29:22):
This is why Because ultimately, even though we all
have the same kinds of pathwaysin our body, how those pathways
get used and how those pathwaysget expressed are extremely
unique.
They are extremely individual.
Speaker 1 (29:35):
I feel like you can compare that to.
You know, we all live in theworld.
Let's say we all live in Iowa.
We all have the same resources,but we all live very different
lives.
Our body is choosing to go downthis rope.
Sometimes we can't control it.
Right and there's things, butif we figure out how we can,
Exactly, exactly.
Speaker 2 (29:54):
And there's things we can control, there's things we
can't.
So absolutely figuring out howto leverage the ones that we can
control and then the ones thatwe can't, well, screw it, we
can't control it anyway.
So let's not blame people forthe things we can't control, but
actually focus on the stuff wecan.
And that's where, absolutelyyeah, and that's exactly where
some of these treatments likemedications and things like that
(30:15):
, have a role.
But even I think this is themost fascinating thing surgery,
like a surgical procedure thatwe do on people, has an impact
on how their genes are expresseddown the road.
Speaker 1 (30:26):
Yeah, that is the crazy part.
Speaker 2 (30:28):
Isn't that crazy.
And it's so cool because Ithink everyone who goes through
this process sees that in actionand this is a little bit of
that under the hood, why ithappens.
Speaker 1 (30:36):
Right, absolutely.
Speaker 2 (30:38):
Yeah.
Speaker 1 (30:39):
Well, thank you, for I know you're like going to that
was a lot, but no, for thepeople that really are trying to
figure out why.
Yeah, and that I talked in theprevious episode about your old
dad was at the gym and gotjudged for having bariatric
surgery.
She could listen and be likeman.
This is this is why, yeah, Shutyour mouth.
Speaker 2 (31:02):
Yeah, shut your mouth because, like, your body is
basically becoming a laboratory,you're turning your body into a
factory for changing and forbecoming healthier and for
converting what things have madeit challenging for you and for
your body to be where you wantit to be and making those things
work better.
And I think people should becongratulated for converting
their body into a laboratoryhonestly and allowing those
(31:25):
changes to happen.
I think it's really cool?
Speaker 1 (31:26):
Yeah, absolutely.
Thank you for the sciencelesson.
Speaker 2 (31:29):
Oh, you're so welcome .
I promise not to do too many ofthese.
Speaker 1 (31:31):
I promise Because, yes, I definitely want to know
why we are the way we are.
People that are obese don'twant to be obese.
Speaker 2 (31:38):
Well, and the thing is, obesity isn't something to
want or not want or somethinglike that.
Really, even I think it'sweight is complicated, as we are
learning, and for some people,even if they do the exact same
thing that somebody else does,their body is going to interpret
it very differently and carryit out very differently and
they're going to have a verydifferent weight as a result.
(31:59):
And it is, I think, true thatwhen people have a BMI over 30,
if they're not, likeprofessional athletes or
otherwise, super heavy withmuscle mass and things like that
, there are things that arehappening in bodies that make it
more difficult to avoid certainkinds of metabolism diseases
(32:20):
and then make it easier forpeople who have BMI under 30 to
have more healthy cells and havemore healthy gene expression
and things like that.
But to say that it applies toeveryone across the board is not
correct, and certainly to saythat it's anyone's fault that
their bodies are doing that iscompletely bogus, absolutely so,
if nothing else, I hope that'sthe takeaway that hey, guess
(32:41):
what?
We've got some things that wecan do about it with medications
and surgery and lifestyle, andthat we're constantly developing
more, because this is a growingfield in every possible way,
and I'm thankful for it, becausethe more we know, the better we
can all do.
Speaker 1 (32:55):
Absolutely Thank you for all of that, because I know
it took a while to figure outexactly how you were going to
explain it to people that mayhave no medical or science
background.
So thank you for making that.
Speaker 2 (33:08):
I hope that wasn't totally gobbledygook for
everyone.
No, no.
Speaker 1 (33:12):
And for those that don't want to go that deep, they
don't have to.
Speaker 2 (33:15):
Not at all.
They can skip an episode, skipthis episode and just go.
No, thank you, that is right.
Speaker 1 (33:20):
Well, thank you all for listening and we will be
back again.
Thank you.
Speaker 2 (33:24):
Yeah, thank you.
Speaker 1 (33:25):
Bye.
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