Characteristics of bile acid composition in high fat diet-induced nonalcoholic fatty liver disease in obese diabetic rats

Abstract

Bile acid has attracted attention as a signal transmission molecule in energy metabolism. Although a high-fat diet (HFD) or obesity is known to increase hepatic fat content and alter bile acid composition, the changes in bile acid composition due to HFD or obesity remain to be elucidated. We sought to examine the bile acid composition in high fat diet-induced non-alcoholic fatty liver disease (NAFLD) in obese diabetic rats. Eight-week-old male spontaneously diabetic Torii fatty (SDTF) rats or control rats were fed an HFD. Twelve weeks post the commencement of HFD, serum and hepatic bile acid compositions and serum GLP-1 levels, which is stimulated by the secondary bile acid deoxycholic acid (DCA), were measured. The correlation between the bile acid composition and serum GLP-1 levels was also examined. While serum and hepatic levels of cholic acid (CA), a primary bile acid, tended to decrease in HFD-fed control rats, they were significantly decreased in HFD-fed SDTF rats. Hepatic CYP8B1, which plays a role in CA synthesis, the mRNA levels were significantly decreased in HFD-fed control and SDTF rats. In contrast, while serum and hepatic DCA levels were not changed in HFD-fed control rats, they were decreased in HFD-fed SDTF rats. Hepatic DCA/CA did not change in HFD-fed SDTF rats, but significantly increased in HFD-fed control rats. While serum GLP-1 levels were not changed in SDTF rats, they were significantly increased in HFD-fed control rats. Hepatic DCA/CA tended to correlate with serum GLP-1 levels, which tended to negatively correlate with the hepatic triglyceride content in SDTF rats. These results indicate that relatively increased DCA might contribute to an increase in serum GLP-1 levels, which inhibits hepatic steatosis in NAFLD.

Versatile Triad Alliance: Bile Acid, Taurine and Microbiota

“…Consequently, CA administration increased the ratio of mainly gram-positive Firmicutes to gram-negative Bacteroidetes [ 204 ]. A similar impact on microbiota has been observed as a consequence of HFD-feeding, which is known for triggering increased BA levels [ 205 , 206 ] and is also the case for obesity [ 207 , 208 ]. Importantly, bacteria can be trained and adapt to the presence of BAs [ 199 , 209 , 210 , 211 ], but conditioning the microbiome by applying HFD can amplify host energy harvest and inflammation [ 208 , 212 , 213 ].…”

New Insights in the Control of Fat Homeostasis: The Role of Neurotensin

“…Bile acid circulation is altered in obesity [68][69][70]. Recent experiments investigated the role of NT in mediating the association between HFD-induced decreases in plasma bile acid levels and the presence of obesity, using whole body knockout mice for the NT gene [71].…”

High-Amylose Corn Starch Regulated Gut Microbiota and Serum Bile Acids in High-Fat Diet-Induced Obese Mice

“…Indeed, substantial evidence has already demonstrated that an elevation in circulating bile acids levels seems to indicate improved energy homeostasis. For example, decreased circulating bile acids were observed in HFD-fed SD rats [ 58 ]. Particularly, HFD feeding was also found to lower circulating levels of CA, DCA [ 58 ], ω-muricholic acid (MCA), and α-MCA [ 59 ].…”

“…For example, decreased circulating bile acids were observed in HFD-fed SD rats [ 58 ]. Particularly, HFD feeding was also found to lower circulating levels of CA, DCA [ 58 ], ω-muricholic acid (MCA), and α-MCA [ 59 ]. In contrast, this HFD-induced decrease in plasma bile acids could be improved in neurotensin-deficient mice [ 60 ].…”