Increased visceral adiposity is a pivotal component of the metabolic syndrome. Differential gene expression patterns of fat-derived peptides (FDPs) in visceral fat and subcutaneous fat have been characterized in the fasting state. Here we examined whether delivery of nutrients differentially affects the expression of FDPs in visceral fat versus subcutaneous fat (in the fed state). We increased the rate of glucose flux into adipose tissue of normal rats (n = 16) by hyperglycemia or hyperinsulinemia using the clamp technique. Glucose uptake was associated with increased expression of FDPs, including resistin ( approximately 5-fold), adiponectin ( approximately 2-fold), leptin ( approximately 15-fold), plasminogen activating inhibitor-1 ( approximately 10-fold), and angiotensinogen ( approximately 4-fold) in visceral fat, but markedly less in subcutaneous fat. Cytokine expression derived mainly from vascular/stromal/macrophage components of adipose tissue was less dramatically increased. Infusion of glucosamine amplified the results obtained by increasing glucose uptake into adipose tissue, suggesting that flux through the hexosamine biosynthetic pathway may serve as a mechanism for "nutrient sensing." Nutrient-dependent expression of FDPs in visceral fat was also associated with increased plasma levels of several FDPs. Because a biologic sensing pathway can dynamically couple daily food intake to abnormal plasma levels of important FDPs, we challenge the practice of obtaining plasma levels after fasting to assess risk factors for metabolic syndrome.