@article{b1a736cc89034b4fb74f86e021649e02,
title = "Relationships between Adipose Mitochondrial Function, Serum Adiponectin, and Insulin Resistance in Persons with HIV after 96 Weeks of Antiretroviral Therapy",
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.",
keywords = "AIDS, adiponectin, insulin resistance, mitochondria, mtDNA haplogroup",
author = "Todd Hulgan and Ramsey, {Benjamin S.} and Koethe, {John R.} and Samuels, {David C.} and Mariana Gerschenson and Libutti, {Daniel E.} and Sax, {Paul E.} and Daar, {Eric S.} and McComsey, {Grace A.} and Brown, {Todd T.}",
note = "Funding Information: Supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under Award Number UM1 AI068634, UM1 AI068636, and UM1 AI106701. A5224s was also supported by NIH grants AI065348, AI38855, AI069434, MD000173, GM007601, GM113134, and MD007601. Adiponectin and insulin assays, and the analyses reported here were supported by NIH grant R21 DK101342 and by the Vanderbilt Student Research and Training Program (SRTP) in Diabetes and Obesity, Kidney Disease, and Digestive Disease (T35 DK007383). The ACTG Human DNA Repository is also supported by CTSA award No. UL1 TR000445 from the National Center for Advancing Translational Sciences. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Allergy and Infectious Diseases, the National Institutes of Diabetes and Digestive and Kidney Diseases, the National Center for Advancing Translational Sciences, or the National Institutes of Health. Study medications for A5202 were provided by Abbott Pharma-ceuticals, Bristol-Myers Squibb, Gilead Sciences, and GlaxoSmithKline. Computed tomography scans for A5224 s were funded by Gilead Sciences and GlaxoSmithKline. Funding Information: T.T.B. has served as a consultant to Gilead Sciences, Merck & Co., Bristol-Myers Squibb, ViiV Healthcare, EMD-Serono, and Theratechnologies. G.A.M. has served as a consultant and received grant support from Gilead, ViiV, and Merck. J.R.K. receives funding from Gilead Sciences Inc. E.S.D. has served as a consultant for Bristol-Myers Squibb, Gilead, Janssen, Merck, Theratechnologies, Teva, and ViiV and received research support from Gilead, Merck, and ViiV. The remaining authors have no conflicts of interest to disclose. Publisher Copyright: {\textcopyright} 2018 Wolters Kluwer Health, Inc.",
year = "2019",
month = mar,
day = "1",
doi = "10.1097/QAI.0000000000001926",
language = "English (US)",
volume = "80",
pages = "358--366",
journal = "Journal of Acquired Immune Deficiency Syndromes",
issn = "1525-4135",
publisher = "Lippincott Williams and Wilkins",
number = "3",
}