Gastric bypass surgery is protective from high-fat diet-induced non-alcoholic fatty liver disease and hepatic endoplasmic reticulum stress

J. D. Mosinski, M. R. Pagadala, A. Mulya, H. Huang, O. Dan, H. Shimizu, E. Batayyah, Rish Pai, P. R. Schauer, S. A. Brethauer, J. P. Kirwan

Research output: Contribution to journalArticle

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Abstract

Aim: High-fat diets are known to contribute to the development of obesity and related co-morbidities including non-alcoholic fatty liver disease (NAFLD). The accumulation of hepatic lipid may increase endoplasmic reticulum (ER) stress and contribute to non-alcoholic steatohepatitis and metabolic disease. We hypothesized that bariatric surgery would counter the effects of a high-fat diet (HFD) on obesity-associated NAFLD. Methods: Sixteen of 24 male Sprague Dawley rats were randomized to Sham (N = 8) or Roux-en-Y gastric bypass (RYGB) surgery (N = 8) and compared to Lean controls (N = 8). Obese rats were maintained on a HFD throughout the study. Insulin resistance (HOMA-IR), and hepatic steatosis, triglyceride accumulation, ER stress and apoptosis were assessed at 90 days post-surgery. Results: Despite eating a HFD for 90 days post-surgery, the RYGB group lost weight (-20.7 ± 6%, P < 0.01) and improved insulin sensitivity (P < 0.05) compared to Sham. These results occurred with no change in food intake between groups. Hepatic steatosis and ER stress, specifically glucose-regulated protein-78 (Grp78, P < 0.001), X-box binding protein-1 (XBP-1) and spliced XBP-1 (P < 0.01), and fibroblast growth factor 21 (FGF21) gene expression, were normalized in the RYGB group compared to both Sham and Lean controls. Significant TUNEL staining in liver sections from the Obese Sham group, indicative of accelerated cell death, was absent in the RYGB and Lean control groups. Additionally, fasting plasma glucagon like peptide-1 was increased in RYGB compared to Sham (P < 0.02). Conclusion: These data suggest that in obese rats, RYGB surgery protects the liver against HFD-induced fatty liver disease by attenuating ER stress and excess apoptosis.

Original languageEnglish (US)
Pages (from-to)141-151
Number of pages11
JournalActa Physiologica
Volume217
Issue number2
DOIs
StatePublished - Jun 1 2016
Externally publishedYes

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Endoplasmic Reticulum Stress
Gastric Bypass
High Fat Diet
Liver
Fatty Liver
Ambulatory Surgical Procedures
Insulin Resistance
Obesity
Eating
Apoptosis
Glucagon-Like Peptide 1
Bariatric Surgery
Metabolic Diseases
In Situ Nick-End Labeling
Sprague Dawley Rats
Non-alcoholic Fatty Liver Disease
Liver Diseases
Fasting
Triglycerides
Cell Death

Keywords

  • Apoptosis
  • NAFLD
  • Obesity
  • Rats
  • RYGB

ASJC Scopus subject areas

  • Physiology

Cite this

Gastric bypass surgery is protective from high-fat diet-induced non-alcoholic fatty liver disease and hepatic endoplasmic reticulum stress. / Mosinski, J. D.; Pagadala, M. R.; Mulya, A.; Huang, H.; Dan, O.; Shimizu, H.; Batayyah, E.; Pai, Rish; Schauer, P. R.; Brethauer, S. A.; Kirwan, J. P.

In: Acta Physiologica, Vol. 217, No. 2, 01.06.2016, p. 141-151.

Research output: Contribution to journalArticle

Mosinski, JD, Pagadala, MR, Mulya, A, Huang, H, Dan, O, Shimizu, H, Batayyah, E, Pai, R, Schauer, PR, Brethauer, SA & Kirwan, JP 2016, 'Gastric bypass surgery is protective from high-fat diet-induced non-alcoholic fatty liver disease and hepatic endoplasmic reticulum stress', Acta Physiologica, vol. 217, no. 2, pp. 141-151. https://doi.org/10.1111/apha.12640
Mosinski, J. D. ; Pagadala, M. R. ; Mulya, A. ; Huang, H. ; Dan, O. ; Shimizu, H. ; Batayyah, E. ; Pai, Rish ; Schauer, P. R. ; Brethauer, S. A. ; Kirwan, J. P. / Gastric bypass surgery is protective from high-fat diet-induced non-alcoholic fatty liver disease and hepatic endoplasmic reticulum stress. In: Acta Physiologica. 2016 ; Vol. 217, No. 2. pp. 141-151.
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AU - Pagadala, M. R.

AU - Mulya, A.

AU - Huang, H.

AU - Dan, O.

AU - Shimizu, H.

AU - Batayyah, E.

AU - Pai, Rish

AU - Schauer, P. R.

AU - Brethauer, S. A.

AU - Kirwan, J. P.

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