Running Title: Ghrelin Activity and Obesity

Ghrelin is a stomach hormone that stimulates growth hormone (GH) secretion, adiposity and food intake. Gastric ghrelin production and secretion are regulated by caloric intake, ghrelin secretion increases during fasting, decreases with re-feeding and is reduced by diet-induced obesity. The aim of our study was to test the hypotheses that an increase in body adiposity 1) will exert an inhibitory role in the reduction of gastric ghrelin synthesis and secretion during a chronic high fat (HF) diet; and, 2) that a chronic HF diet will suppress the rise in circulating ghrelin levels in response to acute fasting. Adult male Sprague-Dawley rats were fed either a standard AIN-76A (~5-12 % calories-fat) or a HF diet (~45 % calories-fat). The effect of an increased adiposity on gastric ghrelin homeostasis was assessed by comparing stomach ghrelin production and plasma ghrelin levels in obese and non-obese rats fed a HF diet. HF diet fed, non-obese rats were generated by administration of triiodothyronine (T3) to lower body fat accumulation. Findings indicate that an increased fat mass per se does not exert an inhibitory action on ghrelin homeostasis during HF diets. Additionally, the magnitude of the plasma ghrelin increment to fasting was not blunted, indicating that a presumed, endogenous signal for activation of ingestive behavior remains intact in spite of excess stored calories in HF fed rats