Cold-induced conversion of cholesterol to bile acids in mice shapes the gut microbiome and promotes adaptive thermogenesis
Abstract
Adaptive thermogenesis is an energy-demanding process that is mediated by cold-activated beige and brown adipocytes, and it entails increased uptake of carbohydrates, as well as lipoprotein-derived triglycerides and cholesterol, into these thermogenic cells. Here we report that cold exposure in mice triggers a metabolic program that orchestrates lipoprotein processing in brown adipose tissue (BAT) and hepatic conversion of cholesterol to bile acids via the alternative synthesis pathway. This process is dependent on hepatic induction of cytochrome P450, family 7, subfamily b, polypeptide 1 (CYP7B1) and results in increased plasma levels, as well as fecal excretion, of bile acids that is accompanied by distinct changes in gut microbiota and increased heat production. Genetic and pharmacological interventions that targeted the synthesis and biliary excretion of bile acids prevented the rise in fecal bile acid excretion, changed the bacterial composition of the gut and modulated thermogenic responses. These results identify bile acids as important metabolic effectors under conditions of sustained BAT activation and highlight the relevance of cholesterol metabolism by the host for diet-induced changes of the gut microbiota and energy metabolism.
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Hepatic BAs can be induced by cold exposure.
“Besides their role in the digestion of dietary lipids, hepatic BAs can be induced by cold exposure 96.”
From Inter‐organ communication: a gatekeeper for metabolic health (2019) · cites this paper as [96]
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- Authors
- Worthmann, A., John, C., Rühlemann, M. C., Baguhl, M., Heinsen, F.-A., Schaltenberg, N., Heine, M., Schlein, C., Evangelakos, I., Mineo, C., Fischer, M., Dandri, M., Kremoser, C., Scheja, L., Franke, A., Shaul, P. W., & Heeren, J.
- Affiliations
- University Medical Center Hamburg-Eppendorf (DE)
- Christian-Albrechts-Universität zu Kiel (DE)
- The University of Texas Southwestern Medical Center (US)
- Universität Hamburg (DE)
- Phenex Pharmaceuticals (Germany) (DE)
- ORCID
- Venue
- Nature Medicine
- Published
- 2017-06-12
- Volume
- 23
- Issue
- 7
- Pages
- 839-849
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W2625485505
- Cited by
- 318
- References
- 53
- Citations by year
- 2026: 24 · 2025: 31 · 2024: 33 · 2023: 41 · 2022: 38 · 2021: 42 · 2020: 41 · 2019: 32 · 2018: 29 · 2017: 7
- FWCI
- 22.05
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Keywords
- cold exposure, cholesterol metabolism, bile acids, adaptive thermogenesis, brown adipose tissue, gut microbiota, CYP7B1, fecal bile acid excretion, lipoprotein processing, beige adipocytes, energy metabolism, host-microbiota interactions
- MeSH terms
- Gastrointestinal Microbiome, Cytochrome P450 Family 7, ATP-Binding Cassette Sub-Family B Member 4, Alanine Transaminase, Animals, Aspartate Aminotransferases, Bile Acids and Salts, Adipose Tissue, Brown, Calorimetry, Indirect, Cholesterol, Cold Temperature, Humans, Liver, Obesity, Receptors, LDL, RNA, Ribosomal, 16S, Steroid Hydroxylases, Blotting, Western, Case-Control Studies, Mice, Knockout, ATP Binding Cassette Transporter, Subfamily B, Reverse Transcriptase Polymerase Chain Reaction, Gene Expression Profiling, Thermogenesis, Mice
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