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Biology of obesity resistance and factors influencing weight gain in humans and animals.

TOPICS DISCUSSED:

Historical views on obesity: In some cultures, like northern Africa or Stone Age societies, high body fat signaled status or attractiveness due to food scarcity, unlike today’s focus on leanness amid calorie abundance.
Energy balance components: Metabolizable energy (95% absorption on average, but varying 1-11%) and unabsorbed nutrients excreted as waste significantly influence weight.
Obesity resistance in animals: Inbred mouse strains show wide variation in weight gain on high-fat diets, often somewhat uncoupled from overeating, suggesting roles for feed efficiency, energy expenditure, or waste rather than intake alone.
Genetic & twin studies: Monozygotic twins overfed 1,000 extra calories daily vary widely in weight gain (4-13 kg), indicating genetic influences, while mouse litter size affects lifelong obesity propensity via early-life programming.
Bloodborne factors & hormones: Parabiosis studies led to leptin’s discovery for defending against weight loss, but evolutionary logic suggests systems also prevent excess gain, though modern environments may weaken this.
Human thinness research: Constitutionally thin people snack more, move less, yet have better cardiometabolic health, but we don’t yet understand why.
GLP-1 drugs & future directions: These slow gut transit and suppress appetite, but obesity’s root causes remain unclear; emerging thinness studies could inform prevention beyond drugs.

ABOUT THE GUEST: Jens Lund, PhD is a postdoctoral researcher at the University of Copenhagen’s Novo Nordisk Foundation Center for Basic Metabolic Research.

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Obesity Resistance & Leanness | Ep. 284

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