Secretin-Activated Brown Fat Mediates Prandial Thermogenesis to Induce Satiation

Summary The molecular mediator and functional significance of meal-associated brown fat (BAT) thermogenesisremains elusive. Here, we identified the gut hormone secretinas a non-sympathetic BAT activator mediating prandial thermogenesis, which consequentiallyinduces satiation, thereby establishing a gut- secretin-BAT-brain axis in mammals with a physiological role of prandial thermogenesisin the control of satiation. Mechanistically, meal-associated rise in circulating secretin activates BAT thermogenesisby stimulating lipolysisupon binding to secretin receptorsin brown adipocytes, which is sensed in the brain and promotes satiation. Chronic infusion of a modified human secretintransiently elevates energy expenditure in diet-induced obesemice. Clinical trials with human subjects showed that thermogenesisafter a single-meal ingestion correlated with postprandial secretinlevels and that secretininfusions increased glucose uptakein BAT. Collectively, our findings highlight the largely unappreciated function of BAT in the control of satiation and qualify BAT as an even more attractive target for treating obesity.