FXR activation reverses insulin resistance and lipid abnormalities and protects against liver steatosis in Zucker (fa/fa) obese rats

Obesity diabetes and the role of bile acids in metabolism

“…Bariatric surgery was found to increase bile acids, but a hypocaloric diet, which induced similar weight loss, was associated with a reduction in the level of uncongugated bile acids [32] , suggesting that bile acid changes are not the main reason for improvement in glucose tolerance following gastric bypass operations. FXR activation of L cells in the ileum by the bile acids may be one mechanism involved in the improvement of diabetes [33] . On the other hand, microbiota convert primary bile acids into secondary bile acids, and it is the secondary bile acids that downregulate FXR most effectively [34] .…”

Effect of Peucedanum japonicum Thunb Extract on High-fat Diet-induced Obesity and Gene Expression in Mice

“…Furthermore, administration of bile acids to mice increased energy expenditure in the brown adipose tissue and skeletal muscle 31 . In another study, FXR activation protected Zucker fa/fa obese rats from body weight gain and fat deposition in the liver and muscle tissue and reversed insulin resistance 32 . The enterohepatic circulation of bile acid, therefore, exerts important physiological effects on whole body lipid homeostasis.…”

Non-Alcoholic Fatty Liver Disease: The Effect of Bile Acids and Farnesoid X Receptor Agonists on Pathophysiology and Treatment

“…63 OCA has been studied in a rabbit model of the metabolic syndrome and in the Zucker rat model of obesity where administration of OCA improved glucose and insulin tolerance and decreased steatohepatitis. 64,65 Furthermore, FXR activation by OCA decreased hepatic expression of genes involved in fatty acid synthesis including sterol regulatory element binding protein-1, reduced TNF-α levels and elevated peroxisome-proliferator activated receptor alpha expression, which therefore led to an improvement in the NASH phenotype. 53,65 OCA therapy also reduced inflammation in a FXR deficient model of autoimmune hepatitis and prevented hepatic stellate cell activation by inhibiting osteopontin production.…”

“…64,65 Furthermore, FXR activation by OCA decreased hepatic expression of genes involved in fatty acid synthesis including sterol regulatory element binding protein-1, reduced TNF-α levels and elevated peroxisome-proliferator activated receptor alpha expression, which therefore led to an improvement in the NASH phenotype. 53,65 OCA therapy also reduced inflammation in a FXR deficient model of autoimmune hepatitis and prevented hepatic stellate cell activation by inhibiting osteopontin production. 66,67 In the thioacetamide rat model of fibrosis, OCA prevented fibrosis progression, reversed fibrosis and cirrhosis development, and significantly reduced portal hypertension.…”