Relationships Between Adipose Mitochondrial Function, Serum Adiponectin, and Insulin Resistance in Persons With HIV After 96 Weeks of Antiretroviral Therapy
Year: 2018
Type: article
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.
Institutions: Vanderbilt University, Vanderbilt University Medical Center, University of South Carolina, University of Hawaiʻi at Mānoa, Brigham and Women's Hospital, Harvard University, University of California, Los Angeles, The Lundquist Institute, Harbor–UCLA Medical Center, University Hospitals Cleveland Medical Center, Case Western Reserve University, Johns Hopkins University
Language: English
Subfield: Emergency Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: ACT Government, National Institutes of Health, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, National Center for Advancing Translational Sciences, National Institute on Minority Health and Health Disparities
Awards: G1050281965, G1323720961, G136441228, G1688481553, G2019238319, G2785878885, G3045663399, Bioscience Research Infrastructure Development for Grant Enhancement and Success, G3672534956, G374818150, UW Clinical HIV Integrated Research Program, Training in Molecular and Cell Biology and Biochemistry, G4235820391, G4553935269, G5268332287, G5555245466, The Center for Native and Pacific Health Disparities Research, G650174051, G681742546, The Vanderbilt Institute for Clinical and Translational Research (VICTR), G857487509, Ola HAWAII, Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections, AIDS Clinical Trial Group Laboratory Center, Statistical and Data Management Center (SDMC), Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections (ACTG), COBRE-DIABETES, Vanderbilt Diabetes Research Center, G961682679
OpenAlex ID: W2905138275