Loss of FXR Protects against Diet-Induced Obesity and Accelerates Liver Carcinogenesis in ob/ob Mice

Zhang, Yanqiao; Ge, Xuemei; Heemstra, Lydia A.; Chen, Weidong; Xu, Jiesi; Smith, Joseph L.; Ma, Huiyan; Kasim, Neda; Edwards, Peter A.; Novak, Colleen M.

doi:10.1210/me.2011-1157

Cited by 113 publications

(96 citation statements)

References 35 publications

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“…Consequently, the administration of BA restores the BA pool and reverses the GW4064-induced metabolic effects ( 89 ). In line with this concept, FXR defi ciency has been shown to protect from genetic and diet-induced obesity ( 50,90 ) and to improve glucose homeostasis by increasing peripheral glucose clearance and adipose tissue insulin sensitivity ( 50 ). The deletion of hepatic FXR has no protective effect ( 50 ), highlighting the importance of extra-hepatic FXR.…”

Section: Fxr and Atherosclerosismentioning

confidence: 95%

Bile acid receptors as targets for the treatment of dyslipidemia and cardiovascular disease

Porez

Prawitt²,

Gross³

et al. 2012

Journal of Lipid Research

255

173

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Section: Fxr and Atherosclerosismentioning

confidence: 95%

Bile acid receptors as targets for the treatment of dyslipidemia and cardiovascular disease

Porez

Prawitt²,

Gross³

et al. 2012

Journal of Lipid Research

255

173

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“…In contrast, Fxr-deficient mice on an Apoe À/À genetic background developed increased atherosclerosis (Hanniman et al, 2005). Nevertheless, in general it appears that Fxr-deficient mice fed a high-fat diet or bred on a genetically obese background (ob/ob) are protected against obesity and exhibit improved glucose homeostasis compared with control mice (Parseus et al, 2016;Prawitt et al, 2011;Zhang et al, 2012). Still, the interaction between FXR and specific macronutrients warrants further investigation.…”

Section: Microbial Regulation Of Host Metabolic Processes Through Fxrmentioning

confidence: 99%

Intestinal Crosstalk between Bile Acids and Microbiota and Its Impact on Host Metabolism

et al. 2016

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The gut microbiota is considered a metabolic "organ" that not only facilitates harvesting of nutrients and energy from the ingested food but also produces numerous metabolites that signal through their cognate receptors to regulate host metabolism. One such class of metabolites, bile acids, is produced in the liver from cholesterol and metabolized in the intestine by the gut microbiota. These bioconversions modulate the signaling properties of bile acids via the nuclear farnesoid X receptor and the G protein-coupled membrane receptor 5, which regulate numerous metabolic pathways in the host. Conversely, bile acids can modulate gut microbial composition both directly and indirectly through activation of innate immune genes in the small intestine. Thus, host metabolism can be affected through microbial modifications of bile acids, which lead to altered signaling via bile acid receptors, but also by altered microbiota composition.

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“…The study also provided evidence for the dysregulation of the FXR-axis with elevated transcription of Fxr and Fgf15 evident in obese animals. Links between FXR regulation and energy metabolism [63] may point to a mechanism by which the microbiota generally influences weight gain [15] .…”

Section: Obesity and Overweightmentioning

confidence: 99%

Disease-Associated Changes in Bile Acid Profiles and Links to Altered Gut Microbiota

Joyce

Gahan²

2017

Dig Dis

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The gastrointestinal microbiota plays a central role in the host metabolism of bile acids through deconjugation and dehydroxylation reactions, which generate unconjugated free bile acids and secondary bile acids respectively. These microbially generated bile acids are particularly potent signalling molecules that interact with host bile acid receptors (including the farnesoid X receptor, vitamin D receptor and TGR5 receptor) to trigger cellular responses that play essential roles in host lipid metabolism, electrolyte transport and immune regulation. Perturbations of microbial populations in the gut can therefore profoundly alter bile acid profiles in the host to impact upon the digestive and signalling properties of bile acids in the human superorganism. A number of recent studies have clearly demonstrated the occurrence of microbial disturbances allied to alterations in host bile acid profiles that occur across a range of disease states. Intestinal diseases including irritable bowel syndrome, inflammatory bowel disease (IBD), short bowel syndrome and Clostridium difficile infection all exhibit concurrent alterations in the composition of the gut microbiota and changes to host bile acid profiles. Similarly, extraintestinal diseases and syndromes such as asthma and obesity may be linked to aberrant bile acid profiles in the host. Here, we focus upon recent studies that highlight the links between alterations to gut microbial communities and altered bile acid profiles across a range of diseases from asthma to IBD.

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Loss of FXR Protects against Diet-Induced Obesity and Accelerates Liver Carcinogenesis in ob/ob Mice

Cited by 113 publications

References 35 publications

Bile acid receptors as targets for the treatment of dyslipidemia and cardiovascular disease

Bile acid receptors as targets for the treatment of dyslipidemia and cardiovascular disease

Intestinal Crosstalk between Bile Acids and Microbiota and Its Impact on Host Metabolism

Disease-Associated Changes in Bile Acid Profiles and Links to Altered Gut Microbiota

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