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Vertical Sleeve Gastrectomy Attenuates the Progression of Non-Alcoholic Steatohepatitis in Mice on a High-Fat High-Cholesterol Diet

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Abstract

Objective

To determine whether vertical sleeve gastrectomy (VSG) attenuates fibrosis in mice on a high-fat high-cholesterol (HFHC) diet.

Background

Bariatric surgery mitigates non-alcoholic steatohepatitis in 85–90% of obese patients. While animal models demonstrate similar results on a high-fat diet, none have observed the effects of bariatric surgery on a combined HFHC diet.

Methods

Mice on a HFHC diet were used to confirm the development of hepatic fibrosis at 8 (n = 15) and 24 (n = 15) weeks. A separate cohort of mice on a HFHC diet for 12 weeks was subjected to either VSG (n = 18) or sham (n = 12) operations and remained on a HFHC diet for an additional 20 weeks. Changes in weight, dyslipidemia, and the development of steatosis and fibrosis were documented. Serum was obtained for bile acid analysis by liquid chromatography and mass spectrometry, while hepatic gene expression by RT-PCR was performed to evaluate intrahepatic lipid metabolism.

Results

Hepatic steatosis and fibrosis developed after 8 weeks on the HFHC diet. After VSG, mice demonstrated a sustained decrease in weight with a significant decrease in fibrosis compared to sham mice. Serum total cholesterol, HDL, and LDL were significantly reduced following surgery, while serum bile acids were significantly elevated. Intra-hepatic cholesterol excretion was not upregulated based on hepatic gene expression of CYP7A1 and ABCG5/8.

Conclusions

VSG attenuates the development of hepatic fibrosis in diet-induced obese mice, presumably through enhancement of cholesterol elimination at the intestinal level.

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Financial Support

The research reported in this publication was financially supported by the Children’s Discovery Institute, Seed Grant Program (EW); NIH (grants R01 DK102110, R01 DK107533, and R01 DK062357; NIH P01 AI120944 (JWKW)); and the Dumont Research Foundation.

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Authors and Affiliations

  1. Division of Pediatric Gastroenterology, Hepatology, and Nutrition, David Geffen School of Medicine, UCLA, Los Angeles, CA, 90095, USA

    Emily Whang

  2. Division of Liver and Pancreas Transplantation, Department of Surgery, The Dumont-UCLA Transplantation Center, David Geffen School of Medicine, UCLA, 77-120 CHS, 10833 Le Conte Ave., Los Angeles, CA, 90095, USA

    Yuan Liu, Shoichi Kageyama, Haofeng Ji & Jerzy W. Kupiec-Weglinski

  3. Division of Liver Surgery, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

    Yuan Liu

  4. Center for Human Nutrition, David Geffen School of Medicine, UCLA, Los Angeles, CA, 90095, USA

    Shih Lung Woo, Jieping Yang, Rupo Lee & Zhaoping Li

  5. Division of General Surgery, Department of Surgery, David Geffen School of Medicine, UCLA, Los Angeles, CA, 90095, USA

    Yijun Chen

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  1. Emily Whang
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  2. Yuan Liu
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  10. Jerzy W. Kupiec-Weglinski
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Corresponding authors

Correspondence to Emily Whang or Jerzy W. Kupiec-Weglinski.

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The animal studies were approved by the Institutional Animal Care and Use Committee at UCLA.

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The authors declare that they have no conflict of interest.

Ethical Statement

All applicable institutional and/or national guidelines for the care and use of animals were followed.

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Whang, E., Liu, Y., Kageyama, S. et al. Vertical Sleeve Gastrectomy Attenuates the Progression of Non-Alcoholic Steatohepatitis in Mice on a High-Fat High-Cholesterol Diet. OBES SURG 29, 2420–2429 (2019). https://doi.org/10.1007/s11695-019-03860-1

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  • DOI: https://doi.org/10.1007/s11695-019-03860-1

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