Microbiota-induced obesity requires farnesoid X receptor.

Authors:
Ava Parséus, Nina Sommer, Felix Sommer, Robert Caesar, Antonio Molinaro, Marcus Ståhlman, Thomas U Greiner, Rosie Perkins, Fredrik Bäckhed
Year of publication:
2016
Volume:
-
Issue:
-
Issn:
0017-5749
Journal title abbreviated:
GUT
Journal title long:
Gut : journal of the British Society of Gastroenterology
Impact factor:
19.819
Abstract:
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.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.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.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.