-We investigated the effect of subdiaphragmatic vagal deafferentation (SDA) on food intake, body weight gain, and metabolism in obese (fa/fa) and lean (Fa/?) Zucker rats. Before and after recovery from surgery, food intake and body weight gain were recorded, and plasma glucose and insulin were measured in tail-prick blood samples. After implantation of a jugular vein catheter, an intravenous glucose tolerance test (IVGTT) was performed, followed by minimal modeling to estimate the insulin sensitivity index. Food intake relative to metabolic body weight (g/kg 0.75 ) and daily body weight gain after surgery were lower (P Ͻ 0.05) in SDA than in sham obese but not lean rats. Before surgery, plasma glucose and insulin concentrations were lower (P Ͻ 0.05) in lean than in obese rats but did not differ between surgical groups within both genotypes. Four weeks after surgery, plasma glucose and insulin were still similar in SDA and sham lean rats but lower (P Ͻ 0.05) in SDA than in sham obese rats. IVGTT revealed a downward shift of the plasma insulin profile by SDA in obese but not lean rats, whereas the plasma glucose profile was unaffected. SDA decreased (P Ͻ 0.05) area under the curve for insulin but not glucose in obese rats. The insulin sensitivity index was higher in lean than in obese rats but was not affected by SDA in both genotypes. These results suggest that elimination of vagal afferent signals from the upper gut reduces food intake and body weight gain without affecting the insulin sensitivity index measured by minimal modeling in obese Zucker rats. food intake; insulin sensitivity; minimal modeling; obesity THE ZUCKER FATTY RAT (fa/fa) rat is homozygous for a mutation in the leptin receptor gene (29). Leptin inhibits the activity of neuropeptide Y and stimulates the expression of proopiomelanocortin and the cocaine-and amphetamine-regulated transcript (CART), resulting in reduced food intake and increased energy expenditure. In the obese Zucker rat, the signal from leptin is not transduced. Neuropeptide Y activity becomes chronically increased, and hardly any CART expression can be found in the arcuate nucleus. This leads to increased food intake and decreased energy expenditure and provides an internal milieu that promotes the accretion of body fat (38). The obese Zucker rat develops severe obesity and pronounced hyperinsulinemia with relatively mild hyperglycemia (6, 37). Long-lasting hyperinsulinemia is responsible for changes in target tissue sensitivity to the glucose regulatory effect of insulin and may contribute to profound insulin resistance (12,38). Secondary changes consist of hyperlipemia with elevated concentrations of plasma triglycerides and plasma cholesterol, increased number and size of adipocytes and pancreatic islets, hepatic steatosis, and an increased activity of parasympathetic efferents accompanied by a decreased activity of sympathetic nerves (12,13,38).Vagal afferents provide the major neuroanatomical link between the gut, which digests and absorbs ingested nutrients, and the centr...