Relationship of fat distribution with adipokines in human immunodeficiency virus infection

Abstract

Background and methods: HIV-infected patients receiving antiretroviral therapy often develop changes in body fat distribution; the dominant change is reduction in sc adipose tissue (SAT). Because adipose tissue makes important hormones involved in whole-body energy metabolism, including leptin and adiponectin, we examined plasma concentrations and their relationship to regional adiposity measured by magnetic resonance imaging in 1143 HIV-infected persons (803 men and 340 women) and 286 controls (151 men and 135 women) in a cross-sectional analysis of the FRAM study.

Results: Total and regional adiposity correlated positively with leptin levels in HIV-infected subjects and controls (P < 0.0001). In controls, total and regional adiposity correlated negatively with adiponectin. In HIV-infected subjects, adiponectin was not significantly correlated with total adiposity, but the normal negative correlation with visceral adipose tissue and upper trunk SAT was maintained. However, leg SAT was positively associated with adiponectin in HIV-infected subjects. Within the lower decile of leg SAT for controls, HIV-infected subjects had paradoxically lower adiponectin concentrations compared with controls (men: HIV 4.1 microg/ml vs. control 7.5 microg/ml, P = 0.009; women: HIV 7.8 microg/ml vs. control 11.6 microg/ml, P = 0.037). Even after controlling for leg SAT, exposure to stavudine was associated with lower adiponectin, predominantly in those with lipoatrophy.

Conclusion: The normal relationships between adiponectin levels and total and leg adiposity are lost in HIV-infected subjects, possibly due to changes in adipocyte function associated with HIV lipodystrophy, whereas the inverse association of adiponectin and visceral adipose tissue is maintained. In contrast, the relationship between adiposity and leptin levels appears similar to controls and unaffected by HIV lipodystrophy.

Figure 1

Distribution of leg SAT and adiponectin levels. Distribution of height-normalized leg SAT is shown by histogram with smoothed density curve created using kernel density estimation. Decile reference line was defined using cutoffs from the control group, with men and women done separately, as described in Materials and Methods. A, Men; B, women. Light bars and dashed lines represent control subjects. Dark bars and solid lines represent HIV-infected subjects. Analysis was age restricted, and those with recent OI were excluded.

Figure 2

Adiponectin levels in HIV-infected subjects by quartile of leg SAT and stavudine duration. Median adiponectin levels in HIV-infected subjects are plotted as a function of quartiles of leg SAT based on control cutoff points. Regression line based on control subjects (Q1–Q4) illustrates that HIV-infected subjects with normal amounts of leg SAT (Q2–Q4) are similar to controls. White bars represent no stavudine exposure; gray bars represent less than 2 yr of stavudine exposure; black bars represent 2 or more years of stavudine exposure. Dashed line represents trend line for controls. Full cohort of all HIV-infected subjects are included.