Vertical sleeve gastrectomy reduces hepatic steatosis while increasing serum bile acids in a weight‐loss‐independent manner

• Published in: Obesity (Silver Spring, Md.) Vol. 22; no. 2; pp. 390 - 400
• Main Authors: Myronovych, Andriy, Kirby, Michelle, Ryan, Karen K., Zhang, Wujuan, Jha, Pinky, Setchell, Kenneth DR, Dexheimer, Phillip J., Aronow, Bruce, Seeley, Randy J., Kohli, Rohit
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01-02-2014
• Subjects: Acids; Animals; Bile Acids and Salts - blood; Bile Acids and Salts - metabolism; Caloric Restriction; Cholic Acid - blood; Cholic Acid - metabolism; Diet, High-Fat - adverse effects; Down-Regulation; Fatty Liver - etiology; Fatty Liver - prevention & control; Gastroplasty; Gene Expression Profiling; Gene Expression Regulation; Lipogenesis; Liver; Liver - metabolism; Liver - pathology; Liver - physiopathology; Male; Mice; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease; Obesity; Obesity - metabolism; Obesity - pathology; Obesity - physiopathology; Obesity - surgery; Postoperative period; Postprandial Period; Random Allocation; Rodents; Taurochenodeoxycholic Acid - blood; Taurochenodeoxycholic Acid - metabolism; Triglycerides - metabolism; Up-Regulation; Weight control; Weight Loss
• ISSN: 1930-7381; 1930-739X
• DOI: 10.1002/oby.20548

Objective
Our objective was to investigate the role of bile acids in hepatic steatosis reduction after vertical sleeve gastrectomy (VSG).
Design and Methods
High fat diet (HFD)‐induced obese C57Bl/6 mice were randomized to VSG, Sham operation (Sham), Sham operation with pair feeding to VSG (Sham‐PF), or nonsurgical controls (Naïve). All mice were on HFD until sacrifice. Mice were observed postsurgery and data for body weight, body composition, metabolic parameters, serum bile acid level and composition were collected. Further hepatic gene expression by mRNA‐seq and RT‐PCR analysis was assessed.
Results
VSG and Sham‐PF mice lost equal weight postsurgery while VSG mice had the lowest hepatic triglyceride content at sacrifice. The VSG mice had elevated serum bile acid levels that positively correlated with maximal weight loss. Serum bile composition in the VSG group had increased cholic and tauroursodeoxycholic acid. These bile acid composition changes in VSG mice explained observed downregulation of hepatic lipogenic and bile acid synthetic genes.
Conclusion
VSG in obese mice results in greater hepatic steatosis reduction than seen with caloric restriction alone. VSG surgery increases serum bile acids that correlate with weight lost postsurgery and changes serum bile composition that could explain suppression of hepatic genes responsible for lipogenesis.