Increased de novo hepatic lipogenesis in human immunodeficiency virus infection

Marc K. Hellerstein, Carl Grunfeld, Kenneth Wu, Mark Christiansen, Suzanne Kaempfer, Cathy Kletke, Cedric H L Shackleton

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200 Scopus citations

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 lipoproteinfatty acids by gas chromatography-mass spectrometry. Circulating tumor necrosis factor (TNF), interleukin-1 (IL-I), interferonα (IFNα), 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 IFNα 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 IFNα 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.

Original languageEnglish (US)
Pages (from-to)559-565
Number of pages7
JournalJournal of Clinical Endocrinology and Metabolism
Volume76
Issue number3
StatePublished - Mar 1993

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

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    Hellerstein, M. K., Grunfeld, C., Wu, K., Christiansen, M., Kaempfer, S., Kletke, C., & Shackleton, C. H. L. (1993). Increased de novo hepatic lipogenesis in human immunodeficiency virus infection. Journal of Clinical Endocrinology and Metabolism, 76(3), 559-565.