A1 Refereed original research article in a scientific journal
Secretin-Activated Brown Fat Mediates Prandial Thermogenesis to Induce Satiation
Authors: Li YG, Schnabl K, Gabler SM, Willershauser M, Reber J, Karlas A, Laurila S, Lahesmaa M, Din MU, Bast-Habersbrunner A, Virtanen KA, Fromme T, Bolze F, O'Farrell LS, Alsina-Fernandez J, Coskun T, Ntziachristos V, Nuutila P, Klingenspor M, Klingenspor M
Publisher: CELL PRESS
Publication year: 2018
Journal: Cell
Journal name in source: CELL
Journal acronym: CELL
Volume: 175
Issue: 6
First page : 1561
Last page: 1574.e12
Number of pages: 26
ISSN: 0092-8674
DOI: https://doi.org/10.1016/j.cell.2018.10.016
Abstract
The molecular mediator and functional significance of meal-assosiated brown fat (BAT) thermogenesis remains elusive. Here, we identified the gut hormone secretin as a non-synmpathetic 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, 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.
The molecular mediator and functional significance of meal-assosiated brown fat (BAT) thermogenesis remains elusive. Here, we identified the gut hormone secretin as a non-synmpathetic 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, 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.
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