Role of insulin and free fatty acids in the regulation of ob gene expression and plasma leptin in normal rats.

Objective: It is under debate whether free fatty acids (FFAs) play an independent role in the regulation of adipose cell functions. In this study, we evaluated whether leptin secretion induced by FFA is due directly to an increased FFA availability or whether it is mediated by insulin levels.

Research Methods And Procedures: To test this hypothesis, we compared the effects of six different experimental designs, with different FFA and insulin levels, on plasma leptin: euglycemic clamp, euglycemic clamp + FFA infusion, FFA infusion alone, FFA + somatostatin infusion, somatostatin infusion alone, and saline infusion.

Results: Our results showed that euglycemic clamp, FFA infusion, or both in combination induced a similar increment of circulating leptin (3.31 +/- 0.30, 3.40 +/- 0.90, and 3.35 +/- 0.80 ng/mL, respectively). Moreover, the inhibition of FFA-induced insulin increase by means of somatostatin infusion completely abolished the rise of leptin in response to FFA (1.05 +/- 0.30 vs. 3.40 +/- 0.90 ng/mL, p < 0.001).

Discussion: In conclusion, our data showed that the effects of high FFA levels on plasma leptin were mediated by the rise of insulin concentration. These data confirm a major role for insulin in the regulation of leptin secretion from rat adipose tissue and support the hypothesis that leptin secretion is coupled to net triglyceride synthesis in adipose tissue.