Roux‐en‐Y Gastric Bypass Surgery Prevents Diet‐Induced Hepatic Steatosis and Endoplasmic Reticulum Stress in the Liver of Obese Rats

Abstract

Obesity is associated with hepatic lipid accumulation, which may increase endoplasmic reticulum stress and contribute to insulin resistance. We hypothesized that bariatric surgery would counter the effects of diet‐induced obesity and prevent steatosis and endoplasmic reticulum (ER) stress in the liver. Sixteen adult male Sprague‐Dawley rats were randomized to Sham (N=8) or Roux‐en‐Y gastric bypass (RYGB) surgery (N=8), and compared to a lean control (N=8) group. Rats were fed a high fat diet for 90 days and insulin resistance was assessed by oral glucose tolerance test and insulin tolerance test. Liver was subsequently assessed for hepatic steatosis, triglyceride accumulation, and ER stress related gene and protein expression. Body weight was decreased by 20.7±6% (P<0.01) and insulin sensitivity was improved (P<0.05) in RYGB versus Sham. ER stress gene and protein expression was normalized in the RYGB group compared to Sham, and was similar to lean controls. Specifically, glucose‐regulated protein 78 (P<0.001), X‐box binding protein‐1 (XBP‐1) and spliced XBP‐1 (P<0.01) was lower in RYGB compared to Sham. Spliced XBP‐1 protein expression was also lower in RYGB versus Sham (P<0.05). These data support the metabolic effectiveness of RYGB surgery and suggest that in rats fed a high fat diet, the prevention of hepatic steatosis and reversal of insulin resistance after RYGB surgery may be mediated through attenuation of hepatic ER stress responses.