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Publication
Gastric bypass surgery is protective from high-fat diet-induced non-alcoholic
fatty liver disease and hepatic endoplasmic reticulum stress.
Authors Mosinski JD, Pagadala MR, Mulya A, Huang H, Dan O, Shimizu H, Batayyah E, Pai
RK, Schauer PR, Brethauer SA, Kirwan JP
Submitted By Submitted Externally on 1/18/2017
Status Published
Journal Acta physiologica (Oxford, England)
Year 2016
Date Published 6/1/2016
Volume : Pages 217 : 141 - 51
PubMed Reference 26663034
Abstract 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., 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., 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)., 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.




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