Gastric Sleeve Surgery Alleviates Obesity-Associated Insulin Resistance and Suppresses Endoplasmic Reticulum Stress in Adipose Tissue of db/db Mice

Abstract

Objective: The aims of this study were to evaluate the effects of gastric sleeve surgery on diabetes remission in db/db mice as well as to determine the underlying mechanisms. Methods: Thirty spontaneously obese, diabetic mice (C57BL/Ksj-db/db) were randomly divided into three groups: sleeve gastrectomy group, sham-operated group, and control db/db group. Ten db/m lean mice were used as nondiabetic littermate controls. All mice were sacrificed on day 28. The fasting plasma glucose, serum insulin, lipid profile, and oral glucose tolerance were measured pre- and postoperatively. Inflammatory cytokines (TNF-α and IL-6), endoplasmic reticulum (ER) stress–related markers (GRP78, PERK, IRE-1, and ATF6), and glucose transporter 4 (GLUT4) in the adipose tissue were assayed. Results: Sleeve gastrectomy significantly reduced the body weight and food intake in the db/db mice. This surgery improved glucose and lipid metabolism, as manifested by the decrease in the fasting plasma glucose level and partial restoration of lipid abnormalities. Also, the surgery improved glucose tolerance and alleviated insulin resistance in db/db mice. Sleeve gastrectomy surgery induced downregulation of the inflammatory adipocytokines TNF-α and IL-6; suppressed expression of the ER stress–related markers GRP78, PERK, IRE-1, and ATF-6; and increased the expression and distribution of GLUT4 in adipose tissue of db/db mice. Conclusion: The improvement in glucose tolerance following sleeve gastrectomy is associated with alleviation of insulin resistance, reduction of inflammatory adipocytokine levels, and suppression of ER stress. Further studies are needed to assess whether these effects have a causal role.