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.
Highlights
With increase in the Westernization of dietary patterns, the prevalence of non-alcoholic fatty liver disease (NAFLD) has risen to 25% in the global population [1]
The body weights of high-fat diet (HFD)-fed SD and spontaneously diabetic Torii fatty (SDTF) rats significantly increased in comparison with normal diet-fed SD and SDTF rats, respectively (Table 1)
With regard to the correlation between hepatic steatosis and bile acid, Aranha et al reported that bile acid levels in the liver, as well as hepatic deoxycholic acid (DCA), CDCA, and cholic acid (CA) levels were elevated in patients with steatohepatitis [18]
Summary
With increase in the Westernization of dietary patterns, the prevalence of non-alcoholic fatty liver disease (NAFLD) has risen to 25% in the global population [1]. Characteristics of bile acid composition in NAFLD NASH is the second leading cause of liver disease among adults awaiting liver transplantation in the United States [2, 3]. Many parallel factors derived from the adipose tissue and gut have been thought to promote liver inflammation [4]. Endoplasmic reticulum stress and its related signaling networks, adipocytokines, and innate immunity are emerging as central factors that regulate key features of NASH [4]
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