Cited by 332Adipose Tissue and MetabolismGut microbiota and healthCholesterol and Lipid Metabolism

Cold-induced conversion of cholesterol to bile acids in mice shapes the gut microbiome and promotes adaptive thermogenesis

Worthmann, Anna, John, Clara, Rühlemann, Malte C, Baguhl, Miriam, Heinsen, Femke-Anouska, Schaltenberg, Nicola, Heine, Markus, Schlein, Christian +9 more·2017·Nature Medicine

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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Crossref · 10.1038/nm.4357

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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)
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
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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