This Scientific focus of the DRC is linked to the IDOM Obesity Unit.
Obesity and metabolism are important diabetes related issues which are the research focus of a significant group of Center investigators. Metabolic research in the Penn DRC extends to the development and function of key metabolic, insulin-responsive tissues such as fat, liver, and muscle.
Highlights From 2006-Present:
Obesity is highly associated with insulin resistance and type 2 diabetes, and basic research focused on central mechanisms and peripheral metabolic tissues including adipose and liver has has flourished in the Penn DRC, as have clinical and translational approaches to obesity. The Transgenic and Chimeric Mouse, Mouse Phenotyping, Physiology, and Metabolism, and RIA/Biomarker Cores have been essential for the success of this Focus Area. Three research highlights during the past period are noted below.
Highlight one: Central control of energy homeostasis. Dr. Bale, funded by a DRC pilot grant, demonstrated the importance of corticotropin releasting hormone and stress in energy homeostasis (Carlin PNAS 2006; J Neuroscience 2010). Dr. Ahima, in collaboration with Dr. Lazar, demonstrated a novel central role of resistin in regulating hepatic metabolism (Singhal J Neuroscience 2007). Moreover, Drs. Grill and Bence demonstrated important roles for glucagon-like peptide-1 as well as leptin signaling outside the hypothalamus in regulation energy metabolism (Hayes Cell Metabolism 2010, 2011). Dr. Bence was supported by a DRC pilot grant.
Highlight two: Regulation of adipocyte differentiation and function. Dr. Lazar utilized genome-wide approaches to elucidate early stages of epigenomic and transcriptional regulation of adipocyte differentiation (Steger Genes Dev 2010) as well as the cistromes for PPARg, the master regulator of adipogenesis and target of antidiabetic drugs, in fat cells and macrophages (Lefterova Genes Dev 2008; MCB 2010) highlighting cell- and species specificity of PPARg function that determine its biological functions. Dr. Seale demonstrated a critical role for PRDM16 in the browning of white adipose tissue (Seale JCI 2011). Dr. Seale is funded by a DRC pilot grant.
Highlight three: Translational research in obesity. Drs. Grant, Hakonarson, and Price have collaborated to find novel single nucleotide polymorphisms and copy number variations that contribute to the heritability of obesity in children and adults (Wang Diabetes 2010; Zhao Diabetes 2010). Dr. Teff and colleagues have explored the role of glucose and premenstrual syndrome on hunger and food intake (Teff Physiol Behav 2007; Trout J Women's Health 2008). In addition, Dr. Wadden's group, playing a major role in the LOOK AHEAD trial, has reported one year weight loss success rates (Wadden Obesity 2009), and collaborated on dietary and sleep therapies for obesity with Dr. Foster (Foster Arch Int Med 2009; Foster Ann Int Med 2010). Dr. Foster has also explored policy and school-based interventions (Foster Pediatrics 2008; Foster NEJM 2010).