2. Academic Validation
  3. Secretin-Activated Brown Fat Mediates Prandial Thermogenesis to Induce Satiation

Secretin-Activated Brown Fat Mediates Prandial Thermogenesis to Induce Satiation

  • Cell. 2018 Nov 29;175(6):1561-1574.e12. doi: 10.1016/j.cell.2018.10.016.
Yongguo Li 1,  Katharina Schnabl 2,  Sarah-Madeleine Gabler 2,  Monja Willershäuser 1,  Josefine Reber 3,  Angelos Karlas 3,  Sanna Laurila 4,  Minna Lahesmaa 4,  Mueez U Din 4,  Andrea Bast-Habersbrunner 1,  Kirsi A Virtanen 4,  Tobias Fromme 2,  Florian Bolze 1,  Libbey S O'Farrell 5,  Jorge Alsina-Fernandez 5,  Tamer Coskun 5,  Vasilis Ntziachristos 3,  Pirjo Nuutila 6,  Martin Klingenspor 7
Affiliations

Affiliations

  • 1 Chair for Molecular Nutritional Medicine, TUM School of Life Sciences, Technical University of Munich, Freising, Germany; EKFZ - Else Kröner-Fresenius Center for Nutritional Medicine, Technical University of Munich, Freising, Germany.
  • 2 Chair for Molecular Nutritional Medicine, TUM School of Life Sciences, Technical University of Munich, Freising, Germany; EKFZ - Else Kröner-Fresenius Center for Nutritional Medicine, Technical University of Munich, Freising, Germany; ZIEL - Institute for Food & Health, Technical University of Munich, Freising, Germany.
  • 3 Institute for Biological and Medical Imaging (IBMI), Helmholtz Zentrum München, Neuherberg; Chair for Biological Imaging, Technical University of Munich, Munich, Germany.
  • 4 Turku PET Centre, University of Turku, Turku, Finland.
  • 5 Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN, USA.
  • 6 Turku PET Centre, University of Turku, Turku, Finland; Department of Endocrinology, Turku University Hospital, Turku, Finland.
  • 7 Chair for Molecular Nutritional Medicine, TUM School of Life Sciences, Technical University of Munich, Freising, Germany; EKFZ - Else Kröner-Fresenius Center for Nutritional Medicine, Technical University of Munich, Freising, Germany; ZIEL - Institute for Food & Health, Technical University of Munich, Freising, Germany. Electronic address: [email protected].
PMID: 30449620 DOI: 10.1016/j.cell.2018.10.016
Abstract

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.

Keywords

UCP1; energy balance; gut hormone; heat; inter-organ communication; metabolism; satiation; secretin; secretin receptor; thermogenesis.

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