Secretin-Activated Brown Fat Mediates Prandial Thermogenesis to Induce Satiation

• Published in: Cell Vol. 175; no. 6; pp. 1561 - 1574.e12
• Main Authors: Li, Yongguo, Schnabl, Katharina, Gabler, Sarah-Madeleine, Willershäuser, Monja, Reber, Josefine, Karlas, Angelos, Laurila, Sanna, Lahesmaa, Minna, u Din, Mueez, Bast-Habersbrunner, Andrea, Virtanen, Kirsi A., Fromme, Tobias, Bolze, Florian, O’Farrell, Libbey S., Alsina-Fernandez, Jorge, Coskun, Tamer, Ntziachristos, Vasilis, Nuutila, Pirjo, Klingenspor, Martin
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 29.11.2018
• Subjects: animal disease models; brain; brown adipocytes; brown adipose tissue; clinical trials; digestive system; energy balance; energy expenditure; glucose; gut hormone; heat; heat production; humans; ingestion; inter-organ communication; lipolysis; metabolism; mice; obesity; satiation; satiety; secretin; secretin receptor; secretin receptors; thermogenesis; UCP1; heat; inter-organ communication; thermogenesis; gut hormone; secretin receptor; secretin; UCP1; metabolism; energy balance; satiation
• ISSN: 0092-8674; 1097-4172; 1097-4172
• DOI: 10.1016/j.cell.2018.10.016

The molecular mediator and functional significance of meal-associated brown fat (BAT) thermogenesis remains elusive. Here, we identified the gut hormone secretin as a non-sympathetic BAT activator mediating prandial thermogenesis, which consequentially induces satiation, thereby establishing a gut-secretin-BAT-brain axis in mammals with a physiological role of prandial thermogenesis in the control of satiation. Mechanistically, meal-associated rise in circulating secretin activates BAT thermogenesis by stimulating lipolysis upon binding to secretin receptors in brown adipocytes, which is sensed in the brain and promotes satiation. Chronic infusion of a modified human secretin transiently elevates energy expenditure in diet-induced obese mice. Clinical trials with human subjects showed that thermogenesis after a single-meal ingestion correlated with postprandial secretin levels and that secretin infusions increased glucose uptake in 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. [Display omitted] •Secretin receptor (SCTR) is highly expressed in BAT•Secretin activates BAT thermogenesis through SCTR-PKA-ATGL/HSL pathway•Secretin-activated BAT mediates prandial thermogenesis and induces satiation•Secretin activates human BAT Secretin, a gut hormone secreted while eating a meal, stimulates brown fat thermogenesis and induction of satiation in mice and humans.