The prevalence of overweight children in the US has increased by more than 50% in the last 10 years. Bodyweight is tightly regulated through a negative endocrine feedback loop by communication of signals fromadipose tissue to the CMS. The major health consequence of obesity is metabolic syndrome, defined asabdominal obesity, dyslipidemia, hypertension (HTN), and impaired glucose tolerance (IGT). Hypothalamiccircuits are involved in the regulation of all of these traits. We hypothesize that CMSresistance to insulin andleptin leads; a) to increased food intake and obesity, and b) to traits of metabolic syndrome independent ofthe resultant obesity. The Zucker fatty rat (ZF) is a model of metabolic syndrome with obesity, HTN,dyslipidemia, and IGT. Our objective is to determine how insulin and leptin signaling in the hypothalamusregulates the traits of metabolic syndrome by determining when in post-partum development these traitsoccur. Next, using a gain-of-function approach we will determine if restoration of hypothalamic function canprevent the onset of a) adiposity and b) metabolic syndrome. Thus CNS resistance to insulin and leptin maybe important in the devleopment of obesity and metabolic syndrome in children and adolescents.
|Stafford, John M; Yu, Fang; Printz, Richard et al. (2008) Central nervous system neuropeptide Y signaling modulates VLDL triglyceride secretion. Diabetes 57:1482-90|