HIV protease inhibitor-specific alterations in human adipocyte differentiation and metabolism

Roy J. Kim, Camella G. Wilson, Martin Wabitsch, Mitchell A. Lazar, Claire M. Steppan

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

Objective: Human immunodeficiency virus (HIV) patients on antiretroviral regimens frequently develop a syndrome of abnormal fat distribution, insulin resistance, and dyslipidemia. This lipodystrophic syndrome has been most closely linked to the use of HIV protease inhibitors (PIs). Several mechanisms have been postulated to explain these adverse effects of PIs, based largely on studies of rodent adipocytes. Intriguingly, atazanavir, a newer PI equally effective against HIV, is associated with fewer signs of lipodystrophy. We hypothesized that the less deleterious clinical effects of atazanavir would be reflected in physiological differences observed in PI-treated adipocytes. Research Methods and Procedures: We compared the effects of atazanavir and an older PI associated with lipodystrophy, ritonavir, on differentiation, gene expression, adipocytokine secretion, and insulin signaling in a human adipocyte cell line. Results: Ritonavir inhibited human adipocyte differentiation and induced apoptosis to a greater extent than atazanavir. Treatment of mature adipocytes with ritonavir, but not atazanavir, also selectively decreased insulin signaling. Moreover, ritonavir also selectively decreased expression of adiponectin, an insulin-sensitizing adipocytokine, while inducing interleukin-6, a proinflammatory cytokine implicated in insulin resistance. Discussion: These data suggest that the distinct metabolic side effect profiles of these PIs could be a consequence of their differential effects on adipocyte physiology.

Original languageEnglish (US)
Pages (from-to)994-1002
Number of pages9
JournalObesity
Volume14
Issue number6
DOIs
StatePublished - Jun 2006

Fingerprint

Protease Inhibitors
Adipocytes
Ritonavir
HIV
Lipodystrophy
Adipokines
Insulin
Insulin Resistance
Adiponectin
Dyslipidemias
Rodentia
Interleukin-6
Fats
Atazanavir Sulfate
Apoptosis
Cytokines
Gene Expression
Cell Line
Research

Keywords

  • Adipocyte
  • Human immunodeficiency virus
  • Insulin resistance
  • Lipodystrophy

ASJC Scopus subject areas

  • Endocrinology
  • Medicine (miscellaneous)
  • Endocrinology, Diabetes and Metabolism
  • Nutrition and Dietetics

Cite this

Kim, R. J., Wilson, C. G., Wabitsch, M., Lazar, M. A., & Steppan, C. M. (2006). HIV protease inhibitor-specific alterations in human adipocyte differentiation and metabolism. Obesity, 14(6), 994-1002. https://doi.org/10.1038/oby.2006.114

HIV protease inhibitor-specific alterations in human adipocyte differentiation and metabolism. / Kim, Roy J.; Wilson, Camella G.; Wabitsch, Martin; Lazar, Mitchell A.; Steppan, Claire M.

In: Obesity, Vol. 14, No. 6, 06.2006, p. 994-1002.

Research output: Contribution to journalArticle

Kim, RJ, Wilson, CG, Wabitsch, M, Lazar, MA & Steppan, CM 2006, 'HIV protease inhibitor-specific alterations in human adipocyte differentiation and metabolism', Obesity, vol. 14, no. 6, pp. 994-1002. https://doi.org/10.1038/oby.2006.114
Kim, Roy J. ; Wilson, Camella G. ; Wabitsch, Martin ; Lazar, Mitchell A. ; Steppan, Claire M. / HIV protease inhibitor-specific alterations in human adipocyte differentiation and metabolism. In: Obesity. 2006 ; Vol. 14, No. 6. pp. 994-1002.
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