Bariatric surgeries are hypothesized to produce
weight loss and improve diabetes control by multiple mechanisms including gastric restriction and lower gut stimulation; the relative importance of these mechanisms remains poorly understood. We compared the effects of a typical foregut procedure, sleeve
gastrectomy, (SG) with a primarily hindgut surgery, ileal transposition (IT), alone and together (SGIT), or
sham manipulations, on food intake,
body weight, gut
hormones,
glucose tolerance, and key markers of
glucose homeostasis in peripheral tissues of adult male Sprague-Dawley rats (450-550 g, n = 7-9/group). SG, IT, and SGIT surgeries produced transient reduction in food intake and
weight gain; the effects of SG and IT on intake and
body weight were nonadditive. SG, IT, and SGIT surgeries resulted in increased tissue expression and plasma concentrations of the lower gut
hormones glucagon-like peptide-1 and
peptide YY and decreased plasma
glucose-dependent insulinotropic peptide,
insulin, and
leptin concentrations. Despite transient effects on intake and
weight gain, the SG, IT, and SGIT surgeries produced a significant improvement in
glucose tolerance. In support of glycemic improvements, the
protein abundance of key markers of
glucose metabolism (e.g., GLUT4, PKA, IRS-1) in muscle and adipose tissue were increased, whereas the expression of key gluconeogenic
enzyme in liver (G-6-Pase) were decreased following the surgeries. Therefore, our data suggest that enhanced lower gut stimulation following SG, IT, and SGIT surgeries leads to transient reduction in food intake and
weight gain together with enhanced secretion of lower gut
hormones and improved
glucose clearance by peripheral tissues.