MMPC :: MICROMouse Program Application Abstract

MICROMouse Program Application Abstract

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Role of Melanocortin Signaling in Gastric Bypass-induced Feeding Behavior

Amanda Vanhoose (Nashville, TN)

MICROMouse Program

The growing obesity epidemic occurring worldwide is supported by many variables, including the overconsumption of readily available, highly palatable, and calorically dense foods. Attempts to treat human obesity with diet alterations are met with limited and short-term success, as many physiological changes occur to defend a high body weight. One contributing factor is dietary recidivism due to an up regulation of desire for rewarding foods that have been withdrawn. This behavior resembles relapse to drugs of abuse, lending support to the emerging theory that addictions to drugs of abuse and dietary rewards share some neural correlates. Through mechanisms not well understood, gastric bypass surgeries result in a high success rate of long-term weight loss that is accompanied by a decreased consumption of calorically dense foods. Understanding the physiological changes produced by surgery is warranted to help develop less invasive interventions for the control of adiposity. We hypothesize that rearrangement of the digestive tract alters the afferent gut to brain signal induced by rewarding foods required to support a preference for those foods. Although the signal(s) has yet to be identified, we propose that it will require activation of the melanocortin 4 receptor (MC4R), a known anorexigenic regulator of both homeostatic- and hedonically-driven food intake. Both humans and mice lacking the MC4R exhibit hyperphagia, with a preference for high fat food, and develop obesity resembling that induced by overconsumption of palatable foods. We propose to test the efficacy of Roux-en-Y gastric bypass (RYGB) surgery adapted for mice with respect to alterations in food preference. To assess the role of MC4R in this phenotype and also the potential this surgery carries for treatment of obese patients carrying MC4R mutations, mice carrying one or no active MC4R alleles will be employed. In addition, we propose to analyze alterations in markers of neural activity in response to withdrawal and reinstatement of palatable food after RYGB surgery, to identify neuronal substrates responsible for loss of preference.

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