My lab focuses on the neuroendocrine mechanisms underlying the profound metabolic effects of bariatric surgery. Bariatric surgery has received much attention recently due to its growing clinical application in the severely obese. Bariatric procedures including Roux-en-Y gastric bypass (RYGB), the most commonly performed procedure in the U.S., typically induce substantial and sustained weight loss, improve all measures of obesity-related comorbidity, and improve mortality.
My lab utilizes a rodent model of RYGB and to understand the afferent and efferent neurohormonal mechanisms induced by this procedure and their central target organs and molecular pathways. An understanding of these mechanisms will facilitate the development of endoluminal devices that may offer similarly efficacious, yet less-invasive, therapeutic alternatives to bariatric surgery in the future. To this end, I was involved in the evaluation of the endoluminal sleeve, a device that, when implanted in the duodenum of obese rats, induces body weight loss and improves diabetes.
The human version of this device, the Endobarrier, induces weight loss and improves diabetes in the severely obese and will undergo phase II evaluation in the U.S. in the near future. The current focus of the lab is a dissection of the central and peripheral neuronal circuits required for the effect of RYGB on body weight, feeding behavior, and glucose metabolism. This work involves the phenotypic and molecular profiling of various mouse models after RYGB and complementary surgical models, including ileal transposition and gastric banding.
Stylopoulos, N. and V. Aguirre, Mechanisms of bariatric surgery and implications for the development of endoluminal therapies for obesity. Gastrointest Endosc, 2009.
Goldfine, A.B., S.E. Shoelson, and V. Aguirre, Expansion and contraction: treating diabetes with bariatric surgery. Nat Med, 2009. 15(6): p. 616-7.
Aguirre, V., et al., An endoluminal sleeve induces substantial weight loss and normalizes glucose homeostasis in rats with diet-induced obesity. Obesity (Silver Spring), 2008. 16(12): p. 2585-92.
Aguirre, V., et al., Phosphorylation of Ser307 in insulin receptor substrate-1 blocks interactions with the insulin receptor and inhibits insulin action. J Biol Chem, 2002. 277(2): p. 1531-7.
Aguirre, V., et al., The c-Jun NH(2)-terminal kinase promotes insulin resistance during association with insulin receptor substrate-1 and phosphorylation of Ser(307). J Biol Chem, 2000. 275(12): p. 9047-54.