Microbiome remodelling leads to inhibition of intestinal farnesoid X receptor signalling and decreased obesity
By Fei Li, Changtao Jiang, K. Krausz, Yunfei Li, I. Albert, H. Hao, Kristin M. Fabre, James B. Mitchell, A. Patterson, F. Gonzalez. Nature Communications, 2013
678 citations recorded by the source corpus.
The antioxidant tempol reduces obesity in mice. Here we show that tempol alters the gut microbiome by preferentially reducing the genus Lactobacillus and its bile salt hydrolase (BSH) activity leading to the accumulation of intestinal tauro-β-muricholic acid (T-β-MCA). T-β-MCA is an farnesoid X receptor (FXR) nuclear receptor antagonist, which is involved in the regulation of bile acid, lipid and glucose metabolism. Its increased levels during tempol treatment inhibit FXR signalling in the intestine. High-fat diet-fed intestine-specific Fxr-null (FxrΔIE) mice show lower diet-induced obesity, similar to tempol-treated wild-type mice. Further, tempol treatment does not decrease weight gain in FxrΔIE mice, suggesting that the intestinal FXR mediates the anti-obesity effects of tempol. These studies demonstrate a biochemical link between the microbiome, nuclear receptor signalling and metabolic disorders, and suggest that inhibition of FXR in the intestine could be a target for anti-obesity drugs. Tempol is an antioxidant that reduces the body weight of mice on a high-fat diet. Li et al.now provide a mechanistic link by demonstrating that tempol affects the intestinal microbiota, which leads to a change in the composition of bile acids and suppression of FXR signalling.
Subfields: Immunology, Oncology, Surgery
View Paper: https://www.semanticscholar.org/paper/e358cc008163f16a4afe302a339b816156672a54
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Citations in the corpus
- BugBase predicts organism-level microbiome phenotypes (2017, background): “The microbiomes of various host body-sites have been implicated in many aspects of human health, including metabolism [3,4], immune response [5,6], disease state [7,8] and even behavior [9,10].”
- Lipotoxicity and the gut-liver axis in NASH pathogenesis. (2018, background): “Experimental models of NAFLD revealed that obesemicrobiota led to lower level of T-MCAs and higher activity of FXR, inducing synthesis of ceramides that, as soon as reaches the liver, alters lipid metabolism, leading to FAs accumulation [159, 160].”
- Resveratrol Attenuates Trimethylamine-N-Oxide (TMAO)-Induced Atherosclerosis by Regulating TMAO Synthesis and Bile Acid Metabolism via Remodeling of the Gut Microbiota (2016, background): “Additionally, tempol, an antioxidant and protective agent against radiation, can alter the gut microbiome, leading to the accumulation of intestinal T- MCA, thereby inhibiting intestinal FXR signaling and decreasing obesity (12).”
- Gut Microbiota in Cardiovascular Health and Disease (2017, background): “There is an astonishing chemical diversity to the BA pool, and although the heterogeneity and function of numerous BAs are just beginning to become dissected, several species are now recognized as regulators of energy metabolism through activation of nuclear receptors such as G-protein–coupled BA re”
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