Diet-Dependent Sex Differences in the Response to Bariatric Surgery

Abstract

Despite the well-known efficacy of bariatric surgery in reducing body mass and improving metabolic outcomes, the mechanisms underlying these dramatic effects are not fully understood. Nearly 80% of patients that receive bariatric surgery are women, yet mechanistic pre-clinical studies have focused exclusively on males. Premenopausal women have a reduced risk for obesity-associated co-morbidities and enhanced lipid metabolism. Although both sexes lose weight and benefit metabolically after bariatric surgery, clear physiological sex differences in metabolism suggest the mechanistic pathway to those outcomes are dependent upon sex and hormone status. The goal of this study was to determine the impact of diet- and surgery-induced weight loss on sex differences in glucose regulation and hepatic lipid metabolism. Male and female mice were fed a 60% high-fat (HF) diet 12 weeks before undergoing either vertical sleeve gastrectomy (VSG) or sham surgery. After surgery, mice either remained on a HF diet or were switched to a standard chow diet. Both males and females decreased fat-mass after VSG, yet males showed further body mass loss on a chow diet. Both sexes improved fasting glucose and oral glucose tolerance on a HF diet after VSG, while only males showed further benefit from surgery and chow diet. Despite continued HF diet feeding, male but not female mice show significant improvements in hepatic triglyceride levels after VSG relative to their sham surgery counterparts. However, when mice were switched to a low-calorie chow diet both males and females reduced hepatic triglycerides after VSG. Furthermore, removing female gonadal hormones, via ovariectomy, did not impact hepatic triglyceride levels after VSG. Overall, these data suggest that the impact of surgery on hepatic triglycerides is diet-dependent in females and support the hypothesis that males and females achieve similar metabolic outcome, at least within the liver, via distinct mechanisms. Disclosure C. Hutch: None. D. Stelmak: None. K. Singer: None. D.A. Sandoval: Research Support; Self; Novo Nordisk A/S, Zafgen, Ethicon US, LLC..