After losing weight through dieting, nonobese adults who regain more than 5% of their original weight show higher insulin levels during a glucose test, suggesting their insulin sensitivity returns to...
Mechanism
Synthesis from 1 study
When people lose weight by eating less, their body becomes better at using insulin to control blood sugar — but if they gain back more than 5% of the lost weight, their fat tissue returns and tricks the brain into overeating, while also restarting insulin and growth signals that make the body less...
Most probable mechanism
When people lose weight by eating less, their body produces less insulin and a related hormone called IGF-1, which helps cells respond better to insulin. This also increases a protein that blocks IGF-1, slowing down cellular growth signals. But if they regain more than 5% of the lost weight, fat tissue comes back and causes insulin and IGF-1 levels to rise again, while also making the brain stop responding properly to leptin — a hormone that tells you when you're full. This leads to overeating, more fat storage, and a return to poor insulin control, which shows up as higher insulin levels after eating sugar. These changes are seen in people who regain weight but not in those who keep the weight off (10.2337/dc25-1911).
Caloric restriction reduces adipose tissue mass, lowering leptin secretion and insulin production from pancreatic β-cells (10.2337/dc25-1911)
Reduced insulin and IGF-1 bioavailability increases IGFBP-1 production by the liver, decreasing free IGF-1 and downregulating PI3K/AKT/mTOR nutrient-sensing signaling (10.2337/dc25-1911)
Weight regain exceeding 5% of baseline restores adipose tissue mass, triggering hyperleptinemia and leptin resistance that impairs hypothalamic satiety signaling, promoting hyperphagia and sustained positive energy balance (10.2337/dc25-1911)
Restored adiposity and hyperphagia increase insulin secretion and IGF-1 bioavailability, reactivating mTOR signaling and suppressing autophagy and cellular repair mechanisms (10.2337/dc25-1911)
Reactivated insulin and mTOR signaling impair insulin sensitivity in peripheral tissues, leading to elevated insulin area under the curve during oral glucose tolerance testing (10.2337/dc25-1911)
Evidence from Studies
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