Effect of Vertical Sleeve Gastrectomy in Melanocortin Receptor 4-Deficient Rats
6/10/2012 12:00:00 PM
6/10/2012 2:00:00 PM
, DENOVAN BEGG, SANNE ALTERS, GIJS VAN HAAFTEN, KAREN DURAN, DAVID A.. D'ALESSIO, CAREL LE ROUX, STEPHEN C. WOODS, DARLEEN A. SANDOVAL, ALEXANDRA F. BLAKEMORE, EDWIN CUPPEN, MIEKE VAN HAELST, RANDY J.. SEELEY,
Bariatric surgery is currently the most effective treatment for obesity. Vertical sleeve gastrectomy (VSG), a commonly applied bariatric procedure, involves surgically incising most of the volume of the stomach. In humans, partial loss of melanocortin receptor-4 (
) activity is the most common monogenic correlate of obesity regardless of lifestyle. At present it is unclear whether genetic alteration of MC4R signaling modulates the beneficial effects of VSG. Following VSG, we analyzed body weight, food intake, glucose sensitivity, and macronutrient preference of wild-type and MC4R-deficient (
) rats as compared to sham-operated controls. VSG reduced body weight and fat and improved glucose metabolism, and also shifted preference towards carbohydrates and away from fat. All of this occurred independently of MC4R function. In addition,
was resequenced in forty-six human subjects who underwent VSG. We observed common genetic variations in the coding sequence of
in five subjects. However, none of those variations affected the outcome of VSG. We conclude that the beneficial effect of VSG on body weight and glucose metabolism in rats is independent of MC4R function. Taken together, our rodent and human data suggest that humans with partial or full loss of MC4R may be good candidates for VSG.
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