Sleeve Gastrectomy Induces Loss of Weight and Fat Mass in Obese Rats, but Does Not Affect Leptin Sensitivity

Background & Aims: Surgical intervention produces sustainable weight loss and metabolic improvement in obese individuals. Vertical sleeve gastrectomy (VSG) produces dramatic, sustained weight loss; we investigated whether these changes result from improved sensitivity to leptin. Methods: VSG was performed in Long-Evans rats with diet-induced obesity. Naïve or sham-operated rats, fed either ad libitum or pair-fed with the VSG group, were used as controls. Following surgery, body weights and food intake were monitored. We investigated energy expenditure, meal patterns, leptin sensitivity, and expression of pro-opiomelanocortin/agouti-related peptide/neuropeptide Y in the hypothalamus of the rats. Results: We observed sustained losses in weight and body fat in male and female rats after VSG. Weight loss persisted after the disappearance of a transient, postsurgical food intake reduction. Resting energy expenditure was similar between control and VSG rats. VSG rats maintained their reduced body weights. However, they responded to a chronic food restriction challenge by overeating, which resulted in prerestriction, rather than pre-VSG, body weights. Consistent with lower adiposity, VSG decreased plasma leptin levels. Although VSG slightly improved leptin's anorectic action, the response was comparable to that observed in controls matched for adiposity by caloric restriction. Changes in hypothalamic neuropeptide expression were consistent with the lower body weight and lower leptin levels but cannot account for the sustained weight loss. Conclusions: VSG causes sustained reduction in body weight, which results from loss of fat mass. The maintenance of weight loss observed did not result from changes in sensitivity to leptin.