title: Increased de novo hepatic lipogenesis in human immunodeficiency virus infection.
abstract: We measured de novo lipogenesis in human immunodeficiency virus (HIV) infected men using a newly developed stable isotope method. HIV-infected subjects with a history of weight loss (n = 17, mean weight loss 14.9 +/- 3.2 kg), asymptomatic HIV-seropositive subjects with normal CD4 T-cell counts (n = 7) and healthy HIV seronegative controls (n = 11) were studied. Hepatic lipogenesis was determined by infusion of [2-13C]-acetate, using the recently described xenobiotic probe technique with mass isotopomer analysis. Hepatic acetyl-coenzyme A enrichment was measured by high performance liquid chromatography/mass spectrometry of secreted sulfamethoxazole-acetate, with measurement of incorporation into very low density lipoprotein-fatty acids by gas chromatography-mass spectrometry. Circulating tumor necrosis factor (TNF), interleukin-1 (IL-1), interferon alpha (IFN alpha), insulin, and triglycerides were measured concurrently, and 7-day weighed food records were performed. De novo hepatic lipogenesis was increased 3- to 4-fold in HIV-infected subjects with weight loss compared to normal controls (P < 0.05 for palmitate and stearate in both overnight-fasted and fed states), and was also significantly increased in asymptomatic HIV seropositive subjects. Circulating TNF and IL-1 were not measurable in any subject (detection limit 2 pg/ml for IL-1 and 20 pg/ml for TNF). Serum IFN alpha was measurable in 11 out of 17 subjects with wasting and correlated significantly with de novo lipogenesis in overnight-fasted but not fed states. Serum IFN alpha was unmeasurable in asymptomatic HIV-infected subjects despite elevated lipogenic rates. Serum triglyceride concentrations were elevated in subjects with weight loss (2.09 +/- 0.28 mmol/L) and asymptomatic HIV-positives (1.34 +/- 0.34 mmol/L) in comparison to controls (0.67 +/- 0.08 mmol/L), and correlated with lipogenesis. Food intake correlated inversely with lipogenesis in the overnight-fasted state. We conclude that HIV infection is characterized by abnormal fat anabolism. This applies to subjects with reduced lean body mass and to asymptomatic HIV-positive subjects with normal T-cell counts. The former observation may have implications for the pathophysiology and treatment of the wasting syndrome. The latter observation is consistent with activation of the immune response and a state of viral nonlatency in early HIV disease.
authors.affiliation: Department of Nutritional Sciences, University of California, Berkeley 94720.
authors.forename: M K
authors.initials: MK
authors.lastname: Hellerstein
authors.forename: C
authors.initials: C
authors.lastname: Grunfeld
authors.forename: K
authors.initials: K
authors.lastname: Wu
authors.forename: M
authors.initials: M
authors.lastname: Christiansen
authors.forename: S
authors.initials: S
authors.lastname: Kaempfer
authors.forename: C
authors.initials: C
authors.lastname: Kletke
authors.forename: C H
authors.initials: CH
authors.lastname: Shackleton
mesh_terms: D000328:Adult; D001823:Body Composition; D016207:Cytokines / Q000097:blood; D002149:Energy Intake; D015658:HIV Infections / Q000097:blood / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D007328:Insulin / Q000097:blood; D008055:Lipids / Q000096:biosynthesis*; D008099:Liver / Q000378:metabolism*; D008297:Male; D009994:Osmolar Concentration; D014280:Triglycerides / Q000097:blood
chemical_list: D016207:Cytokines; D007328:Insulin; D008055:Lipids; D014280:Triglycerides