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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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