title: Tumor necrosis factor alpha is associated with insulin-mediated suppression of free fatty acids and net lipid oxidation in HIV-infected patients with lipodystrophy.
abstract: Tumor necrosis factor alpha (TNF-alpha) stimulates lipolysis in man. We examined whether plasma TNF-alpha 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-alpha 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-alpha 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 (R2 = 0.43, P < .001) and controls (R2 = 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-alpha, independently of insulin sensitivity, is associated with attenuated insulin-mediated suppression of FFA and LIPOX in HIV-LIPO, suggesting in turn that TNF-alpha stimulates lipolysis in this syndrome. Furthermore, FFA may be a major determinant of LIPOX in HIV-infected patients on highly active antiretroviral therapy.
authors.affiliation: Department of Infectious Diseases, Hvidovre University Hospital, Hvidovre, DK 2650 Copenhagen, Denmark. sbhau@dadlnet.dk
authors.forename: Steen B
authors.initials: SB
authors.lastname: Haugaard
authors.forename: Ove
authors.initials: O
authors.lastname: Andersen
authors.forename: Steen B
authors.initials: SB
authors.lastname: Pedersen
authors.forename: Flemming
authors.initials: F
authors.lastname: Dela
authors.forename: Mogens
authors.initials: M
authors.lastname: Fenger
authors.forename: Bjørn
authors.initials: B
authors.lastname: Richelsen
authors.forename: Sten
authors.initials: S
authors.lastname: Madsbad
authors.forename: Johan
authors.initials: J
authors.lastname: Iversen
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D001823:Body Composition; D003430:Cross-Sectional Studies; D005230:Fatty Acids, Nonesterified / Q000097:blood*; D015309:Glucose Clamp Technique; D005951:Glucose Tolerance Test; D005990:Glycerol / Q000097:blood; D015658:HIV Infections / Q000097:blood*; D039682:HIV-Associated Lipodystrophy Syndrome / Q000097:blood*; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D018709:Statistics, Nonparametric; D014280:Triglycerides / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; D005990:Glycerol