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Because leptin stimulates nitric oxide (NO) release from the hypothalamus and anterior pituitary gland, we hypothesized that it also might release NO from adipocytes, the principal source of leptin. Consequently, plasma concentrations of leptin and NO, estimated from its metabolites NO₃ and NO₂ (NO₃-NO₂), were measured in adult male rats. There was a linear increase of both leptin and NO₃-NO₂ with body weight that was associated with a parallel rise in fat mass. These findings indicate that release of leptin and NO is directly related to adipocyte mass. Furthermore, there was a parallelism in circadian rhythm of both substances, with peaks at 0130 h and nadirs at 0730 h. Measurement of both leptin and NO₃-NO₂ in plasma from individual rats revealed that NO₃-NO₂ increased linearly with leptin. Incubation of epididymal fat pads with leptin or its i.v. injection in conscious rats increased NO₃-NO₂ release. The …