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

Abstract

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).

Blunted lipolysis and fatty acid oxidation during moderate exercise in HIV-infected subjects taking HAART

“…Therefore, it is unlikely that elevated insulin levels fully accounted for the blunted lipolytic response in HIV-positive subjects during exercise. Last, although not measured, decreased hormone-sensitive lipase activity may have played a role in the lower lipolytic response in HIV-positive subjects (46).…”

“…Plasma insulin and C-peptide concentrations were quantified using radioimmunoassay (13). Fasting serum lipids were quantified as described previously (46). Serum catecholamine concentrations were determined by an isotope-derivative radioenzymatic method (38).…”

Whole-Body Proteolysis Rate Is Elevated in HIV-Associated Insulin Resistance

“…Abdominal (subcutaneous and visceral) fat content was quantified using proton magnetic resonance imaging (Siemens, Iselin, NJ). Each was identified in serial axial images obtained at the level of the L 2 -L 3 interspace, and their areas (in centimeters squared) were measured using Analyze Direct software (21). Areas from eight serial images of the abdomen were averaged.…”

“…Fasting serum nonesterified free fatty acid (FFA) levels were quantified using a commercial assay (Wako Chemicals, Richmond, VA). Fasting serum lipid/ lipoprotein levels were quantified as described previously (21). Fasting serum interleukin (IL)-8 concentrations were quantified using a commercially available antibody bead-based 96-well microplate assay (Bio-Rad Laboratories, Hercules, CA) following the manufacturer's protocol.…”

Alterations in thigh subcutaneous adipose tissue gene expression in protease inhibitor-based highly active antiretroviral therapy

“…Consistent slice localization was accomplished by using the iliac crest as a landmark to position the subject in the magnet. For abdominal scans, 18 serial cross-sectional images (10 mm thick, TR = 205 milliseconds, TE = 4.1 milliseconds) were obtained at the level of the L 3 -L 4 interspace to quantify abdominal SAT and visceral adipose tissue (VAT) areas [15]. For thigh scans, 10 serial cross-sectional images (8 mm thick, TR = 1500 milliseconds, TE = 12 milliseconds) were obtained from a region 10 to 25 cm above the superior border of the medial condyle on the head of the tibia to quantify thigh subcutaneous fat area [16].…”