Tumor necrosis factor α is associated with insulin-mediated suppression of free fatty acids and net lipid oxidation in HIV-infected patients with lipodystrophy

Abstract Tumor necrosis factor α (TNF- α ) stimulates lipolysis in man. We examined whether plasma TNF- α is associated with the degree by which insulin suppresses markers of lipolysis, for example, plasma free fatty acid (FFA) and net lipid oxidation (LIPOX) rate in HIV-infected patients with lipodystrophy (LIPO) and those without (controls). LIPOX was estimated by indirect calorimetry during fasting and steady state of a hyperinsulinemic euglycemic clamp in 36 (18 LIPO and 18 controls) normoglycemic HIV-infected men on highly active antiretroviral therapy. In LIPO, TNF- α correlated with clamp FFA ( r = 0.67, P r = 0.47, P r = 0.69, P r = 0.64, P r = 0.29, P > .05), remained significant after correction for insulin sensitivity. None of these correlations were significant in controls. In all patients, TNF- α correlated with clamp FFA ( r = 0.61, P r = 0.43, P r = 0.43, P R 2 = 0.43, P R 2 = 0.60, P P 's α , independently of insulin sensitivity, is associated with attenuated insulin-mediated suppression of FFA and LIPOX in HIV-LIPO, suggesting in turn that TNF- α stimulates lipolysis in this syndrome. Furthermore, FFA may be a major determinant of LIPOX in HIV-infected patients on highly active antiretroviral therapy.