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

• Published in: Metabolism, clinical and experimental clinical and experimental, 2006-02, Vol.55 (2), p.175-182
• Main Authors: Haugaard, Steen B., Andersen, Ove, Pedersen, Steen B., Dela, Flemming, Fenger, Mogens, Richelsen, Bjørn, Madsbad, Sten, Iversen, Johan
• Format: Article
• Language: English
• Subjects: Adipose Tissue - metabolism; Adult; Blood Glucose - metabolism; Body Composition; Cross-Sectional Studies; Fatty Acids, Nonesterified - blood; Glucose Clamp Technique; Glucose Tolerance Test; Glycerol - blood; HIV Infections - blood; HIV-Associated Lipodystrophy Syndrome - blood; Humans; Insulin - metabolism; Male; Middle Aged; Statistics, Nonparametric; Triglycerides - metabolism; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 0026-0495; 1532-8600
• DOI: 10.1016/j.metabol.2005.08.018

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 < .01), clamp LIPOX ( r = 0.47, P < .05), incremental FFA ( r = 0.69, P < .01), and incremental LIPOX ( r = 0.64, P < .01), all of which, but not the clamp LIPOX correlation ( 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 < .001), clamp LIPOX ( r = 0.43, P < .01), and incremental FFA ( r = 0.43, P < .01), with the 2 former correlations remaining significant after correction for insulin sensitivity. LIPOX and FFA (fasting and clamp values combined) correlated strongly and positively in both LIPO ( R 2 = 0.43, P < .001) and controls ( R 2 = 0.60, P < .0001). Fasting FFA and LIPOX did not differ between study groups; however, the insulin-mediated suppression of FFA and LIPOX was attenuated in LIPO ( P's < .05). Our data indicate that higher TNF- 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.