The arginine‐NO pathway modulates lipolysis in adipose tissues of obese human subjects

Abstract

Previous studies involving high extracellular concentrations of various NO donors (20 μM to 2 mM) showed that they strongly inhibited lipolysis in adipose tissue. However, the physiological significance of these findings remains obscure. On the basis of our recent report that dietary supplementation with L-arginine (the physiological nitrogenous precursor of NO) reduced fat mass in Zucker diabetic fatty rats, the present study was conducted to test the hypothesis that the arginine-NO pathway modulates lipolysis in adipose tissues of obese human subjects. Subcutaneous and omental fat tissues (~100 mg) were obtained from 8 adult women with BMI between 30 and 40 kg/m2, minced into small fragments, and incubated at 37 oC for 3 h in 1 ml of Krebs bicarbonate buffer (pH 7.4) containing 5 mM glucose, 4% BSA, and one of the following: 0, 0.5, 1, 5, 10, 25, 50, 100, or 500 μM sodium nitroprusside (SNP; an NO donor); 0, 0.5 or 2 mM L-arginine; or 5 μM 8-bromo cGMP (a mediator of NO effect). At the end of the incubation, the medium was analyzed for glycerol as an indicator of lipolysis. SNP at 0 to 5 μM dose-dependently increased (P < 0.05) lipolysis by up to 50–54% in both subcutaneous and omental fat tissues, whereas SNP at 25 to 500 μM dose-dependently decreased (P < 0.05) lipolysis by up to 90% in the tissues. L-Arginine at 0.5 and 2 mM increased (P < 0.05) lipolysis by ~ 24% and 50%, respectively, in both fat tissues, whereas 5 μM 8-bromo cGMP stimulated their lipolysis by 47–55%. Our results indicate that physiologic levels of NO increase, while excess levels inhibit, lipolysis in human adipose tissue. The dose-dependent lipolytic effects of NO clarify the discrepancies in the literature regarding a role for NO in fat metabolism. Supported by GRECC-BVAMC, NIH, and Texas A&M.