Project 1: Role of peroxisome proliferation in leptin resistance
Recent data, including those from our laboratories raised the notion that ROS generation is not merely a by-product of substrate oxidation, but it plays a crucial role in modulating cellular responses involved in the regulation of energy metabolism. Specifically, this project focuses on the role of peroxisomes in the regulation of intracellular ROS levels, and their involvement in leptin resistance. The aim of these studies may ultimately uncover treatments of obesity.
Project 2: Role of prolyl carboxypeptidase in metabolism regulation
The major anorexigenic peptide in the hypothalamus is alpha-melanocyte-stimulating hormone (-MSH), the product of the pro-opiomelanocortin (POMC) gene. When released, alpha-MSH is rapidly degraded, a process that is likely to play an important role in melanocortin signaling. We have identified a carboxylase enzyme, prolyl carboxypeptidase (PRCP), which is expressed in the hypothalamus and initiates degradation and inactivation of extracellular alpha-MSH. This project aims to decipher the role of PRCP in metabolism regulation and to uncover its potential for treatment of obesity.
Project 3: Role of Prolyl endopeptidase in glucose homeostasis
Central Prolyl endopeptidase (PREP) expression is particularly elevated in the ventromedial nucleus of the in the hypothalamus, area involved in the regulation of glucose homeostasis. Using an animal model of PREP Knockdown (Prepgt/gt) we have generated, this project aims to decipher the molecular underpinning of Prep’s involvement in the promotion of peripheral glucose metabolism and uncover its potential for treatment of type II diabetes.
Project 4: Role of mitochondrial uncoupling protein 2 in energy and glucose metabolism
Uncoupling protein 2 (UCP2) is an inner membrane mitochondria protein highly expressed in hypothalamic neurons involved in the regulation of energy and glucose homeostasis. Diet-induced obese and diabetic mice as well as genetically obese leptin-deficient mice (ob/ob) have elevated levels of hypothalamic UCP2. Thus, this project aims to decipher the role of UCP2 in energy and glucose homeostasis.