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J Acquir Immune Defic Syndr. 2019 Mar 1;80(3):358-366. doi: 10.1097/QAI.0000000000001926.

Relationships Between Adipose Mitochondrial Function, Serum Adiponectin, and Insulin Resistance in Persons With HIV After 96 Weeks of Antiretroviral Therapy.

Author information

1
Vanderbilt University Medical Center, Nashville, TN.
2
Vanderbilt University School of Medicine, Nashville, TN.
3
University of South Carolina School of Medicine Greenville, Greenville, SC.
4
John A. Burns School of Medicine, University of Hawaii-Manoa, Honolulu, HI.
5
Harvard University, Brigham and Women's Hospital, Boston, MA.
6
David Geffen School of Medicine at UCLA, Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, Los Angeles, CA.
7
University Hospitals Cleveland Medical Center, Case Western Reserve University, Cleveland, OH.
8
Johns Hopkins University, Baltimore, MD.

Abstract

OBJECTIVE:

Some antiretroviral therapy (ART) and HIV itself confer metabolic risk, perhaps through altered mitochondrial function and adipokines. In AIDS Clinical Trials Group study A5224s, adipose mitochondrial DNA (mtDNA) levels decreased on ART, and electron transport chain complex I (CI) and complex IV (CIV) activity decreased. Another study found decreased serum adiponectin on ART with mtDNA mutation m.10398A>G. We hypothesized that decreased adipose tissue mitochondrial function would be associated with lower adiponectin and insulin sensitivity on ART, and m.10398G would influence these changes.

DESIGN:

Retrospective analysis of an ART-naive substudy population from A5224s.

METHODS:

Analyses included adipose mtDNA levels, CI and CIV activity by immunoassay, visceral adipose tissue by computed tomography, and fasting serum glucose at week 0 and week 96 of ART. Fasting insulin and adiponectin were measured from cryopreserved serum using multiplex bead array. Homeostasis model assessment-2 (HOMA2)-IR and HOMA2-%B estimated insulin resistance and β-cell function, respectively. The m.10398A>G mtDNA variant was available from existing genetic data.

RESULTS:

Thirty-seven participants had adipose biopsies at week 0 and week 96. Percent decreases in CIV activity and adiponectin were correlated (Spearman rho 0.41; P = 0.01); this association persisted after controlling for age, sex, body mass index, or visceral adipose tissue in single-covariate regression. HOMA2-IR correlated with decreased CIV (-0.44; P = 0.01) and CI (-0.34; P = 0.05) activity. Among 12 non-Hispanic white persons, m.10398G was associated with decreased adiponectin (P = 0.04).

CONCLUSIONS:

Decreased adipose mitochondrial activity correlated with changes in adiponectin and glucose homeostasis on ART. Previous findings that a mtDNA mutation modulates adiponectin levels in persons with HIV were replicated.

PMID:
30531304
PMCID:
PMC6375746
[Available on 2020-03-01]
DOI:
10.1097/QAI.0000000000001926

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