50. Your Body Is Stuck Burning Fat — And It's Making You Sick (Part 2)

What happens when your body gets stuck burning fat and can't switch back to glucose?

In Part 2, Zane breaks down metabolic inflexibility and explains why being locked into fat-dominant metabolism is not the same as being metabolically healthy.

You'll learn how this pattern affects the muscle, heart, and liver — and how elevated fatty acids can impair glucose oxidation, disrupt insulin signaling, and contribute to insulin resistance, fatty liver disease, and heart failure.

Start with Part 1 first for the ATP and glucose-efficiency breakdown.

01:00 The metabolic signature of insulin resistance 03:30 Why your body should switch between fat and glucose 06:00 The 3 tissues that reveal metabolic inflexibility 08:30 Why Zane changed his mind about low carb 13:30 The real definition of metabolic inflexibility 15:00 Why elevated blood sugar can happen on keto or carnivore 20:00 Heart failure and metabolic disease 22:00 Why failing hearts become more dependent on fat 25:00 Why glucose is not the problem 29:00 The liver and fatty liver disease 33:00 Fatty liver is a metabolic inflexibility problem 34:00 Why the liver starts producing more glucose 40:00 How liver disease progresses 41:00 The muscle, heart, and liver connection 46:00 How to restore glucose oxidation 47:00 Why high-fat, low-carb can mimic metabolic disease

Kelley, D.E. (2005) "Skeletal muscle fat oxidation: timing and flexibility are everything" Journal of Clinical Investigation — JCI25758 / PMC1159159 Used for: Definition of metabolic inflexibility; experimental elevation of plasma FFAs recreating T2D metabolic signature in skeletal muscle; blunted insulin-stimulated glucose oxidation; impaired suppression of lipid oxidation

Ukropcova, B. et al. (2005) "Dynamic changes in fat oxidation in human primary myocytes mirror metabolic characteristics of the donor" Journal of Clinical Investigation — JCI24332 Used for: Formal definition of metabolic inflexibility — insulin-resistant muscle characterized by lower fasting lipid utilization and failure to switch to carbohydrate oxidation in response to insulin

Sun, Q., Lopaschuk, G.D. et al. (2024) "Mitochondrial fatty acid oxidation is the major source of cardiac ATP production in heart failure with preserved ejection fraction" Cardiovascular Research, Volume 120 — PMID 38193548 Used for: Direct radiolabeled substrate measurements in HFpEF; suppressed insulin-stimulated glucose oxidation; increased FAO; decreased PDH phosphorylation confirmed in human h