Neuropeptide Y expression and endogenous leptin concentrations in a dietary model of obesity

Objective: To determine how leptin concentrations and neuropeptide (NPY) are regulated in a model of dietary obesity in relation to relative growth (RG) and relative food consumption(RFC). Research Methods and Procedures: Sprague-Dawley rats were fed a moderately high-fat diet for 14 weeks over which time animals diverged into obesity-prone (OP) and obesity-resistant (OR) populations. RG rates and RFC were calculated weekly. Following the study, an adiposity index was calculated and arcuate nucleus (ARC) NPY expression was determined by in situ hybridization (ISH) or ribonuclease protection (RPA) assays. Results: Body weights were greater in OP rats after 2 weeks on the diet compared to OR rats and remained different throughout the study. RG and RFC were greater in OP rats compared to OR rats only during the first 2 weeks of the study. Leptin concentrations rose in both groups during the experiment, but the increase was greater in OP rats than in OR rats. Insulin changes paralleled those for leptin. ARC NPY mRNA expression was not different between OP and OR rats as measured by ISH and RPA. Discussion: Although NPY expression has been reported to be different initially in OP and OR rats, this difference dissipates following divergence of body weight. RFC and RG data suggest the initial NPY elevation may contribute to increased weight gain of OP rats during the first 2 weeks of the diet. Higher relative leptin concentrations in OP rats may be necessary to normalize differences in adiposity and apparent leptin and insulin resistance of OP rats.