"Anything Meds Can Do, You Can Do Better" Part 4 of 12 - Increased Lipolysis and Lipodystrophy

Increased Lipolysis and Lipodystrophy: Fat Spillover, Insulin Resistance, and What You Can Do

In this episode, we break down Increased Lipolysis and Lipodystrophy in simple terms. Learn how fat spillover blocks insulin, when TZDs help or harm, and the food and exercise steps that work.

This is Part 4 of our 12-part series, “Anything Meds Can Do, You Can Do Better.” Today we dig into Increased Lipolysis and Lipodystrophy—what they mean, why they drive insulin resistance, how certain meds work, and the simple steps you can start now.

Remission from type 2 and prediabetes is real. Let’s go.

Episode in one sentence

When fat breaks down and spills into places it doesn’t belong, it gums up your muscles and liver, blocks insulin and GLUT4, and pushes blood sugar up—but food choices, movement, and smart habits can turn the tide.

What we cover

• What “increased lipolysis” really means (extra fat breakdown and spillover)
• How fat inside muscle makes the “sponge” greasy and insulin can’t work
• Toxic fat byproducts (diacylglycerols and ceramides) and how they block insulin and GLUT4
• Lipodystrophy in plain English (fat stored in the wrong places)
• Fatty liver and why it’s so common with type 2 diabetes
• TZDs (pioglitazone/Actos; rosiglitazone/Avandia): how they work, pros, and serious cons
• Food and exercise that improve insulin sensitivity and PPAR-gamma naturally
• Simple, safe action steps you can start this week

Timestamps

• 0:00 Welcome + series recap
• 1:00 What is increased lipolysis? (fat spillover into muscle)
• 4:00 Toxic fat byproducts block insulin and GLUT4
• 7:00 The “sponge and bacon grease” picture for insulin resistance
• 8:30 Fatty liver (NAFLD) and oxidative stress
• 10:00 Meds: TZDs/Thiazolidinediones and PPAR-gamma
• 14:30 Pros of TZDs (insulin sensitivity, fatty liver support)
• 16:00 Cons of TZDs (fluid retention, heart failure risk)
• 20:00 Who is at higher risk (HF, long diabetes, high A1C, HTN, CAD, CKD, obesity)
• 21:30 Bone loss risk, osteoblasts, and why this matters, especially for women
• 26:00 Food tools: omega-3s, fiber, polyphenols, olive oil, nuts, beans
• 30:00 Saturated vs monounsaturated fats; real peanut butter 101
• 34:30 Exercise: aerobic + resistance, GLUT4, mitochondria, bone health
• 38:00 Your one action for the week
• 39:00 Next episode: increased hepatic glucose production (liver)

Key ideas in simple words

• Increased lipolysis = extra fat breakdown. Lots of free fatty acids (FFAs) float in your blood. They can move into muscle and liver.
• Lipodystrophy = fat stored in the wrong places (like liver, muscle, heart, pancreas) instead of mainly under the skin. That “fat spillover” hurts insulin action.
• Inside muscle, fat droplets break into “toxic byproducts” called diacylglycerols (DAGs) and ceramides. These block insulin signals and stop GLUT4 (the sugar door) from opening. Blood sugar rises.
• Think of muscle as a sponge. Sugar is water. When the sponge is greasy (fat inside), water runs off. The muscles say, “We’re full.” Sugar stays in the blood.
• Fatty liver (NAFLD) is very common with type 2 diabetes. It ties to oxidative stress and the whole “metabolic syndrome” picture.

Meds: the good and the bad (TZDs)

• Names: Thiazolidinediones (TZDs) like pioglitazone (Actos). Rosiglitazone (Avandia) is used less.
• How they work: They turn on a switch in your cell nucleus called PPAR-gamma. This helps:
  • Improve insulin sensitivity
  • Lower FFAs and lipotoxicity
  • Store fat under the skin, not around organs
  • Increase GLUT4 in muscle and fat
  • Ease fatty liver
  • Some studies show fewer repeat strokes/heart attacks in high-risk folks
• Serious cons to know:
  • Fluid and sodium retention → can worsen heart failure
  • Not advised in NYHA class III–IV heart failure (and used with caution in many others)
  • Weight gain
  • Bone loss over time (shifts stem cells toward fat cells, away from bone-building cells, called osteoblasts). This is a big deal for older adults, especially postmenopausal women, due to hip and spine fracture risk.
• Reality check: Many with type 2 diabetes already have heart problems or risk factors (long duration, high A1C, hypertension, CAD, kidney disease, obesity). For a large slice of people, risks may outweigh benefits. Always talk with your clinician.

Natural ways to support PPAR-gamma and improve insulin sensitivity

These are straight from the science and fit real life.

• Omega-3 fats
  • Eat: salmon, sardines, mackerel
  • Or use a quality fish oil (third-party tested for purity)
  • Also: chia seeds, freshly ground flaxseeds
• Polyphe