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

  • Emily WhangEmail author
  • Yuan Liu
  • Shoichi Kageyama
  • Shih Lung Woo
  • Jieping Yang
  • Rupo Lee
  • Zhaoping Li
  • Haofeng Ji
  • Yijun Chen
  • Jerzy W. Kupiec-WeglinskiEmail author
Original Contributions
  • 28 Downloads

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.

Keywords

Vertical sleeve gastrectomy VSG NASH Non-alcoholic steatohepatitis Fibrosis 

Notes

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.

Compliance with Ethical Standards

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

Conflict of Interest

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.

Informed Consent

Does not apply.

Disclosure

The content is solely the responsibility of all the authors and does not necessarily represent the official views of the Children’s Discovery Institute.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Division of Pediatric Gastroenterology, Hepatology, and NutritionDavid Geffen School of Medicine, UCLALos AngelesUSA
  2. 2.Division of Liver and Pancreas Transplantation, Department of SurgeryThe Dumont-UCLA Transplantation Center, David Geffen School of Medicine, UCLALos AngelesUSA
  3. 3.Division of Liver SurgeryRen Ji Hospital, Shanghai Jiao Tong University School of MedicineShanghaiChina
  4. 4.Center for Human NutritionDavid Geffen School of Medicine, UCLALos AngelesUSA
  5. 5.Division of General Surgery, Department of SurgeryDavid Geffen School of Medicine, UCLALos AngelesUSA

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