Kevin D. Beck - US grants

DESCRIPTION (provided by applicant): This application requests support for the Seventh Annual Meeting of the Organization for the Study of Sex Differences (OSSD), to be held April 25-27, 2013 in the greater New York City area, Weehawken NJ. The OSSD is a scientific membership society that was originally established in 2006 as an affiliate of the Society for Women's Health Research (SWHR). In July 2012, the OSSD became independently incorporated and is now under the direct control of the member scientists. The mission of the OSSD is to enhance knowledge of the biological basis of sex/gender differences in health and disease by facilitating interdisciplinary communication and collaboration among scientists and clinicians from diverse scientific and professional backgrounds. The primary goal of the OSSD annual meeting is to provide a forum for scientists to explore aspects of sex differences research at the genetic, molecular, cellular, organ, and systems levels in humans and model systems. The annual meeting consists of three independent symposia (one focused on New Investigators), ten parallel session symposia, and two poster sessions (highlighting the work of new investigators and trainees). The symposium topics for the 2013 meeting include: sex differences in treatment strategies for: epilepsy, cancer-related pain, and aged populations; sex differences in the etiology of multiple sclerosis, renal diseases, cardiac arrhythmias, heart disease, and mental illness; and the role of sex chromosome expression in disease. The Presidential Symposium will focus on Sex Differences in Autism (in conjunction with Autism Speaks), and another symposium will focus on the role of the Centers for Sex Difference Research (supported by the Office for Women's Health Research) in furthering the knowledge gained in the areas concerning sex differences in health and disease . The OSSD Program Committee selected the symposia topics from among proposals submitted by the membership. Proposals were selected on the basis of scientific merit, relevance to the goals of the OSSD, a balance of basic and clinical speakers, and rotation of topics of interest across annual meetings. The size and format of this meeting (150-200 participants) provides an excellent opportunity for networking opportunities and interactive discussions. Funds are requested to support registration fees for invited speakers (established, junior and trainee), travel expenses for junio investigators and trainees, and expenses related to the OSSD Annual Meeting Program Book and necessary audio-visual equipment rentals and associated technical support. The annual meeting program, including speaker and poster abstracts, will be made freely available on the OSSD website. We will partner with the University of Medicine and Dentistry of New Jersey to organize this event and are requesting support from pharmaceutical and biotechnology industry, local businesses, and private donors and foundations as well (to help cover non-NIH costs).

Scientific Abstract Although a 10% weight loss significantly reduces the risk of obesity-associated diabetes and heart disease, fewer than 20% of individuals achieve and maintain this weight loss. Thus, obesity underlies a large portion of health care costs in the United States. Consumption of palatable foods above homeostatic needs (reward-based feeding) is a likely contributor to weight regain. Ventral tegmental area (VTA) dopamine neurons play a key role in reward-based feeding. Metabolic state influences reward circuitry. However the mechanisms underlying this regulation are unclear. The lateral hypothalamic area (LHA) orexin glucose-inhibited (GI) neurons which provide excitatory input to the VTA dopamine neurons may be an important link between metabolic status and reward-based feeding. For example, orexin mediates the fasting-induced increase in reward-based feeding. Our preliminary data show that fasting also reduces the inhibitory effect of glucose on LHA orexin-GI neurons leading to increased activation in low glucose. This proposal tests the hypothesis that weight loss increases activation of LHA orexin-GI neurons by glucose deficit. This change in glucose sensitivity reinforces reward-based feeding by causing persistent changes in glutamate signaling onto the VTA dopamine neurons. As a result pre-prandial glucose decreases could enhance intake of the subsequent meal. Three Specific Aims will test this hypothesis in vitro and in vivo: 1) Determine whether weight loss enhances the response of orexin GI neurons to decreased glucose; 2) Determine whether weight loss enhances synaptic plasticity in VTA dopamine neurons in a glucose and orexin dependent manner; 3) Determine whether increased LHA glucose level attenuates the effects of fasting and weight loss on reward based behavior. These studies will increase understanding of the mechanisms underlying difficulties in achieving and maintaining weight loss.