Secretin-Activated Brown Fat Mediates Prandial Thermogenesis to Induce Satiation
Open accessAbstract
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.
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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.”
From Inter‐organ communication: a gatekeeper for metabolic health (2019) · cites this paper as [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.”
From Inter‐organ communication: a gatekeeper for metabolic health (2019) · cites this paper as [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.”
From Inter‐organ communication: a gatekeeper for metabolic health (2019) · cites this paper as [107]
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.”
From Inter‐organ communication: a gatekeeper for metabolic health (2019) · cites this paper as [107]
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Isolation, Culture, and Functional Analysis of Murine Thermogenic Adipocytes
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Susceptibility to diet-induced obesity at thermoneutral conditions is independent of UCP1
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Do Bariatric Surgeries Enhance Brown/Beige Adipose Tissue Thermogenesis?
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CGI-58: Versatile Regulator of Intracellular Lipid Droplet Homeostasis
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Functional characterization of human brown adipose tissue metabolism
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The gut hormone secretin triggers a gut–brown fat–brain axis in the control of food intake
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Uncoupling Protein 1 Does Not Produce Heat without Activation
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Self-citationThermogenic Brown Fat in Humans: Implications in Energy Homeostasis, Obesity and Metabolic Disorders
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Fatty Acid Metabolite Profiling Reveals Oxylipins as Markers of Brown but Not Brite Adipose Tissue
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Self-citationPurine Nucleotides in the Regulation of Brown Adipose Tissue Activity
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Self-citationBrown Adipose Tissue: A Metabolic Regulator in a Hypothalamic Cross Talk?
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Vagal Sensory Gut–Brain Pathways That Control Eating—Satiety and Beyond
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LncRNA Ctcflos orchestrates transcription and alternative splicing in thermogenic adipogenesis
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Self-citationFood phenolics stimulate adipocyte browning via regulating gut microecology
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Secretin modulates appetite via brown adipose tissue-brain axis
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Self-citationThe Fight Against Obesity Escalates: New Drugs on the Horizon and Metabolic Implications
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Physiological Appetite Regulation and Bariatric Surgery
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Metabolic Factors Determining the Susceptibility to Weight Gain: Current Evidence
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Self-citationLETMD1 is required for mitochondrial structure and thermogenic function of brown adipocytes
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Self-citationPleiotropic Effects of Secretin: A Potential Drug Candidate in the Treatment of Obesity?
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Discovery of small molecule positive allosteric modulators of the secretin receptor
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Molecular and cellular regulation of thermogenic fat
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Effects of Nutrition/Diet on Brown Adipose Tissue in Humans: A Systematic Review and Meta-Analysis
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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
- ORCID
- 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
- bronze
- doi.org
- Licence
- 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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