Cited by 229Adipose Tissue and MetabolismRegulation of Appetite and ObesityAdipokines, Inflammation, and Metabolic Diseases

Secretin-Activated Brown Fat Mediates Prandial Thermogenesis to Induce Satiation

Open access
Li, Yongguo, Schnabl, Katharina, Gabler, Sarah-Madeleine, Willershäuser, Monja, Reber, Josefine, Karlas, Angelos, Laurila, Sanna, Lahesmaa, Minna +11 more·2018·Cell

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.

Integrity signals

Registry

Crossref · 10.1016/j.cell.2018.10.016

Cites

57 of 57 references verified0 citation errors · 0 not checkable

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Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Feeding activates the secretion of periprandial gut hormones, such as CCK, GLP‐1, or secretin.

    “In particular, feeding activates the secretion of periprandial gut hormones, such as CCK, GLP‐1, or secretin 105, 106, 107.”
  • Secretin treatment increases the expression of anorexigenic POMC peptide in the hypothalamus and reduces food intake.

    “Moreover, secretin treatment increases the expression of the anorexigenic proopiomelanocortin (POMC) peptide in the hypothalamus and therefore reduces food intake 107.”
  • A secretin injection in fasted mice directly activates BAT thermogenesis by increasing lipolysis through the cAMP‐PKA pathway.

    “A secretin injection in fasted mice directly activates BAT thermogenesis by increasing lipolysis through the cAMP‐PKA pathway.”
  • Secretin can stimulate BAT thermogenesis in a non‐sympathetic manner and contribute to satiation.

    “Interestingly, secretin can stimulate BAT thermogenesis in a non‐sympathetic manner and contribute to satiation.”

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Authors
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.
Affiliations
  • Else Kröner Fresenius Zentrum für Ernährungsmedizin (DE)
  • Helmholtz Munich (DE)
  • University of Turku (FI)
  • Eli Lilly (United States) (US)
Corresponding author
Klingenspor, Martin
Venue
Cell
Publisher
Elsevier BV
Published
2018-11
Volume
175
Issue
6
Pages
1561-1574.e12
ISSN
0092-8674 (ISSN-L)
OpenAlex
W2900996634
Cited by
228
References
58
Citations by year
2026: 13 · 2025: 21 · 2024: 33 · 2023: 27 · 2022: 35 · 2021: 33 · 2020: 34 · 2019: 27 · 2018: 5
FWCI
17.09
Type
journal article
Language
en
Open access
Locations
  • Cell (publishedVersion)
  • PubMed (publishedVersion)
  • mediaTUM (Technical University of Munich) (submittedVersion)
  • PuSH - Publication Server of Helmholtz Zentrum München (submittedVersion)
Funders
  • Deutsche Forschungsgemeinschaft (KL973/11&12, RTG1482)
  • Else Kröner-Fresenius-Stiftung
  • DFG (RTG1482, NT 3/10-1)
  • Research Council (694968)
  • Academy of Finland (259926, 265204, 292839, 269977)
  • University of Turku
  • Turku University Hospital
  • Åbo Akademi University (European Union, 278373)
Topics
  • Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
  • Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
Keywords
secretin, brown adipose tissue, satiation, gut-brain axis, secretin receptor, lipolysis, energy expenditure, obesity, diet-induced obesity, glucose uptake, postprandial hormone levels
MeSH terms
Animals, Adipose Tissue, Brown, Eating, Humans, Lipolysis, Mice, Obese, Secretin, Mice, Knockout, Thermogenesis, Mice, Adipocytes, Brown, HEK293 Cells

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