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Microbiota-induced obesity requires farnesoid X receptor
Open accessAbstract
Objective: The gut microbiota has been implicated as an environmental factor that modulates obesity, and recent evidence suggests that microbiota-mediated changes in bile acid profiles and signalling through the bile acid nuclear receptor farnesoid X receptor (FXR) contribute to impaired host metabolism. Here we investigated if the gut microbiota modulates obesity and associated phenotypes through FXR. Design: We fed germ-free (GF) and conventionally raised (CONV-R) wild-type and Fxr−/−mice a high-fat diet (HFD) for 10 weeks. We monitored weight gain and glucose metabolism and analysed the gut microbiota and bile acid composition, beta-cell mass, accumulation of macrophages in adipose tissue, liver steatosis, and expression of target genes in adipose tissue and liver. We also transferred the microbiota of wild-type and Fxr-deficient mice to GF wild-type mice. Results: The gut microbiota promoted weight gain and hepatic steatosis in an FXR-dependent manner, and the bile acid profiles and composition of faecal microbiota differed between Fxr−/−and wild-type mice. The obese phenotype in colonised wild-type mice was associated with increased beta-cell mass, increased adipose inflammation, increased steatosis and expression of genes involved in lipid uptake. By transferring the caecal microbiota from HFD-fed Fxr−/−and wild-type mice into GF mice, we showed that the obesity phenotype was transferable. Conclusions: Our results indicate that the gut microbiota promotes diet-induced obesity and associated phenotypes through FXR, and that FXR may contribute to increased adiposity by altering the microbiota composition.
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Metadata
- Authors
- Parséus, A., Sommer, N., Sommer, F., Caesar, R., Molinaro, A., Ståhlman, M., Greiner, T. U., Perkins, R., & Bäckhed, F.
- Venue
- Gut
- Publisher
- BMJ
- Published
- 2016-01-06
- Volume
- 66
- Issue
- 3
- Pages
- 429-437
- ISSN
- 0017-5749 (ISSN-L)
- 1468-3288
- OpenAlex
- W2231949068
- Cited by
- 474
- References
- 19
- FWCI
- 20.77
- Type
- journal article
- Language
- en
- Open access
- hybrid
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