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

Authors

  • Andriy Myronovych,

    1. Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA
    Search for more papers by this author
  • Michelle Kirby,

    1. Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA
    Search for more papers by this author
  • Karen K. Ryan,

    1. Metabolic Diseases Institute, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
    Search for more papers by this author
  • Wujuan Zhang,

    1. Department of Pathology and Laboratory Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA
    Search for more papers by this author
  • Pinky Jha,

    1. Department of Pathology and Laboratory Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA
    Search for more papers by this author
  • Kenneth DR. Setchell,

    1. Department of Pathology and Laboratory Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA
    Search for more papers by this author
  • Phillip J. Dexheimer,

    1. Department of Pediatrics, Division of Biomedical Informatics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA
    Search for more papers by this author
  • Bruce Aronow,

    1. Department of Pediatrics, Division of Biomedical Informatics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA
    Search for more papers by this author
  • Randy J. Seeley,

    1. Metabolic Diseases Institute, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
    Search for more papers by this author
  • Rohit Kohli

    Corresponding author
    1. Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA
    2. Metabolic Diseases Institute, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
    Search for more papers by this author

  • Funding agencies: This work was supported by NIH DK084310, U01 DK08505 (RK), and Ethicon Endo-Surgery (RJS, RK), and NIH P30 DK078392.

  • Conflicts of Interest: RJS receives research support from Ablaris, Johnson and Johnson, Novo Nordisk, and Pfiezer, is a paid speaker for Johnson and Johnson, Merck, Novo Nordisk, and Pfizer, serves as a consultant for Angiogen, Eli Lilly, Johnson and Johnson, Novartis, Novo Nordisk, Takeda and Zafgen, and has equity in Zafgen. RK receives research support from Johnson and Johnson. The other coauthors have no disclosures.

  • Author contributions: AM, MK, and RK conceived and carried out experiments; KKR, KDRS, BA, and RJS conceived experiments and analyzed data. WJ, PJ, and PJD carried out experiments. All authors were involved in writing the paper and had final approval of the submitted and published versions.

Abstract

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.

Ancillary