Visceral adiposity, C-peptide levels, and low lipase activities predict HIV-dyslipidemia

• Published in: American journal of physiology: endocrinology and metabolism Vol. 48; no. 4; pp. E899 - E905
• Main Authors: YARASHESKI, Kevin E, TEBAS, Pablo, CLAXTON, Sherry, MARIN, Donna, COLEMAN, Trey, POWDERLY, William G, SEMENKOVICH, Clay F
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Physiological Society 01.10.2003
• Subjects: Biological and medical sciences; Fundamental and applied biological sciences. Psychology; HIV; Human immunodeficiency virus; Human viral diseases; Infectious diseases; Medical sciences; Peptides; Vertebrates: endocrinology; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; magnetic resonance imaging; aspartyl protease inhibitors; Triacylglycerol lipase; central obesity; Esterases; C-Peptide; metabolic complications; Complication; insulin resistance; Nutritional status; Immunopathology; Obesity; Enzyme; Nutrition disorder; Retroviridae; AIDS; Metabolism; Immune deficiency; Lentivirus; Carboxylic ester hydrolases; acquired immunodeficiency syndrome; Infection; Virus; Peptidases; Target tissue resistance; Viral disease; lipoprotein lipase; Hydrolases; Human immunodeficiency virus
• ISSN: 0193-1849; 1522-1555

Protease inhibitor-based highly active antiretroviral therapy (PI-HAART) has been implicated in dyslipidemia, peripheral insulin resistance, and abnormal adipose tissue deposition in human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome, or AIDS. In vitro evidence indicates that some PIs reduce adipocyte lipoprotein (LPL) and hepatic lipase (HL) expression and activities. We examined whether LPL and HL activities are reduced in HIV-infected patients with dyslipidemia. Fasting serum lipids, glucoregulatory hormones, and postheparin LPL and HL activities, as well as whole body and regional adiposity, were measured in 19 HIV-seronegative controls, 9 HIV+ patients naive to all anti-HIV medications, 9 HIV+ patients naive to PIs, 9 HIV+ patients with prior PI experience but not currently receiving PIs, and 47 HIV+ patients receiving PI-HAART. The PI-HAART group had low LPL and HL activities. However, multiple linear regression analysis indicated that low postheparin LPL activity contributed only partially to HIV-dyslipidemia. Central adiposity and high C-peptide levels (an indicator of high insulin secretion) were stronger predictors of HIV-dyslipidemia. Low LPL and HL activities, by themselves, were insufficient to explain HIV-dyslipidemia because the PI-naive group had low LPL and HL activities but had normal adiposity, C-peptide levels, and serum lipid and lipoprotein levels. HDL-cholesterol was lower in PI-HAART and PI-naive groups than seronegative controls and was directly associated with LPL activity. These findings suggest that HIV-dyslipidemia is mediated primarily by factors that influence triglyceride and lipoprotein synthesis (e.g., central adiposity and hyperinsulinemia) and mediated only partially by factors that influence triglyceride clearance (e.g., lipase activity).