Sex Differences in Body Weight Regulation and Hepatic Insulin Signaling Following Bariatric Surgery and Postoperative Diet in Obese Rats.

Abstract

INTRODUCTION: The global obesity prevalence demands new strategies for its treatment. We evaluated sleeve gastrectomy (SG) and biliopancreatic diversion (BD) effects on body weight and hepatic insulin signaling outcomes in high-fat diet (HFD)-induced obese rats, with attention to postoperative diet and sex. METHODS: Wistar rats received a four-week HFD, then underwent SG or BD. Postoperatively, half of each experimental group remained on HFD and half switched to standard chow for four weeks. Serum glycemia and insulin as well as hepatic GLUT1/GLUT2, IR, p-IR (Tyr1361), Akt, and p-Akt (Ser473) were assessed. RESULTS: SG and BD produced comparable weight loss. However, a switch to standard chow yielded additional weight loss only in females. Postoperative diet did not alter glycemia, aligning with weight-independent, surgery-driven mechanisms. Serum insulin was unchanged in males but decreased in females after SG/BD, with a further decline on chow. At the hepatic level, IR abundance increased in both sexes, whereas IR activation was surgery/diet-sensitive only in males. Conversely, p-Akt/Akt rose with chow only in females, indicating enhanced hepatic insulin sensitivity without a requisite increase in IR phosphorylation. CONCLUSION: Both procedures significantly reduced body weight and lowered blood glucose in males and females. Switching to standard chow further enhanced weight loss and insulin sensitivity in females. Hepatic glucose transporter and signaling responses varied by sex, surgery, and postoperative diet. These findings underscore sex-related, independent effects of surgery and postoperative diet and argue for tailored nutritional management after bariatric procedures.