Monocyte bioenergetic function is associated with body composition in virologically suppressed HIV-infected women

Abstract

Women living with HIV may present with high levels of body fat that are associated with altered bioenergetic function. Excess body fat may therefore exacerbate the bioenergetic dysfunction observed with HIV infection. To determine if body fat is associated with bioenergetic function in HIV, we conducted a cross-sectional study of 42 women with HIV who were virologically suppressed on antiretroviral therapy. Body composition was determined via dual-energy x-ray absorptiometry. Oxygen consumption rate (OCR) of monocytes was sorted from peripheral blood mononuclear cells obtained from participants in the fasting state. Differences in bioenergetic function, as measured by OCR, was assessed using Kruskal-Wallis tests and Spearman correlations adjusted for age, race, and smoking status. Participants were 86% Black, 45.5 years old, 48% current smokers, and 57% were obese (body mass index ≥30). Nearly all women (93%) had >30% total fat mass, while 12% had >50% total fat mass. Elevated levels of total fat mass, trunk fat, and leg fat were inversely correlated with measures of bioenergetic health as evidenced by lower maximal and reserve capacity OCR, and Bioenergetic Health Index. Measures of extracellular acidification (ECAR) in the absence (basal) or maximal (with oligomycin) were positively correlated with measures of bioenergetics, except proton leak, and were negatively correlated with fat mass. Despite virological suppression, women with HIV present with extremely high levels of adiposity that correlate with impaired bioenergetic health. Without effective interventions, this syndemic of HIV infection and obesity will likely have devastating consequences for our patients, potentially mediated through altered mitochondrial and glycolytic function.

Keywords: Bioenergetics; Body composition; HIV; Mitochondria; Obesity; Women.

Graphical abstract

Fig. 1

Distribution of monocyte oxygen consumption rate by percent total body fat tertiles in women living with HIV. Medians are indicated by the solid line. ^†=P<0.07 Kruskal-Wallis result with Dunn test. *=P<0.05 Kruskal-Wallis result with Dunn test.

Fig. 2

Distribution of monocyte oxygen consumption rate by percent leg fat tertiles in women living with HIV. Medians are indicated by the solid line. ^†=P<0.07 Kruskal-Wallis result with Dunn test. *=P<0.05 Kruskal-Wallis result with Dunn test.

Fig. 3

Distribution of monocyte oxygen consumption rate by percent trunk fat tertiles in women living with HIV. Medians are indicated by the solid line. ^†=P<0.07 Kruskal-Wallis result with Dunn test. *=P<0.05 Kruskal-Wallis result with Dunn test.

Fig. 4

Monocyte extracellular acidification rate (ECAR) of monocytes in women living with HIV. (A and B) Distribution of basal and maximal ECAR by percent trunk fat. Medians are indicated by the solid line. ^†=P<0.06 Kruskal-Wallis result with Dunn test. *=P<0.05 Kruskal-Wallis result with Dunn test. (C) Correlation of basal oxygen consumption rate (OCR) with basal ECAR. (D) Correlation of maximal OCR with maximal ECAR.