Li, Y.* ; Schnabl, K.* ; Gabler, S.M.* ; Willershäuser, M.* ; Reber, J. ; Karlas, A. ; Laurila, S.* ; Lahesmaa, M.* ; U Din, M.* ; Bast-Habersbrunner, A.* ; Virtanen, K.A.* ; Fromme, T.* ; Bolze, F.* ; O'Farrell, L.S.* ; Alsina-Fernandez, J.* ; Coskun, T.* ; Ntziachristos, V. ; Nuutila, P.* ; Klingenspor, M.*
Secretin-activated brown fat mediates prandial thermogenesis to induce satiation.
Cell 175, 1561-1574 (2018)
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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Publication type
Article: Journal article
Document type
Scientific Article
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Editors
Keywords
Ucp1 ; Energy Balance ; Gut Hormone ; Heat ; Inter-organ Communication ; Metabolism ; Satiation ; Secretin ; Secretin Receptor ; Thermogenesis; Adipose-tissue Thermogenesis; Food-intake; Cold-acclimation; Gastrointestinal Hormones; Insulin Sensitivity; Energy-expenditure; Glucose; Meal; Adipocytes; Humans
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Language
english
Publication Year
2018
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2018
ISSN (print) / ISBN
0092-8674
e-ISSN
1097-4172
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Volume: 175,
Issue: 6,
Pages: 1561-1574
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Cell Press
Publishing Place
Cambridge, Mass.
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Reviewing status
Peer reviewed
POF-Topic(s)
30205 - Bioengineering and Digital Health
Research field(s)
Enabling and Novel Technologies
PSP Element(s)
G-505500-001
G-505593-001
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Erfassungsdatum
2018-12-03