{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T16:37:22Z","timestamp":1773419842912,"version":"3.50.1"},"reference-count":40,"publisher":"The Endocrine Society","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,9,1]]},"abstract":"<jats:p>HIV infection and its therapy are associated with disorders of lipid metabolism and bioenergetics. Previous work has suggested that viral protein R (Vpr) may contribute to the development of lipodystrophy and insulin resistance observed in HIV-1\u2013infected patients. In adipocytes, Vpr suppresses mRNA expression of peroxisomal proliferator-activating receptor-\u03b3 (PPAR\u03b3)-responsive genes and inhibits differentiation. We investigated whether Vpr might interact with PPAR\u03b2\/\u03b4 and influence its transcriptional activity. In the presence of PPAR\u03b2\/\u03b4, Vpr induced a 3.3-fold increase in PPAR response element-driven transcriptional activity, a 1.9-fold increase in pyruvate dehydrogenase kinase 4 (PDK4) protein expression, and a 1.6-fold increase in the phosphorylated pyruvate dehydrogenase subunit E1\u03b1 leading to a 47% decrease in the activity of the pyruvate dehydrogenase complex in HepG2 cells. PPAR\u03b2\/\u03b4 knockdown attenuated Vpr-induced enhancement of endogenous PPAR\u03b2\/\u03b4-responsive PDK4 mRNA expression. Vpr induced a 1.3-fold increase in mRNA expression of both carnitine palmitoyltransferase I (CPT1) and acetyl-coenzyme A acyltransferase 2 (ACAA2) and doubled the activity of \u03b2-hydroxylacyl coenzyme A dehydrogenase (HADH). Vpr physically interacted with the ligand-binding domain of PPAR\u03b2\/\u03b4 in vitro and in vivo. Consistent with a role in energy expenditure, Vpr increased state-3 respiration in isolated mitochondria (1.16-fold) and basal oxygen consumption rate in intact HepG2 cells (1.2-fold) in an etomoxir-sensitive manner, indicating that the oxygen consumption rate increase is \u03b2-oxidation\u2013dependent. The effects of Vpr on PPAR response element activation, pyruvate dehydrogenase complex activity, and \u03b2-oxidation were reversed by specific PPAR\u03b2\/\u03b4 antagonists. These results support the hypothesis that Vpr contributes to impaired energy metabolism and increased energy expenditure in HIV patients.<\/jats:p>","DOI":"10.1210\/me.2012-1370","type":"journal-article","created":{"date-parts":[[2013,7,11]],"date-time":"2013-07-11T04:59:04Z","timestamp":1373518744000},"page":"1564-1576","source":"Crossref","is-referenced-by-count":13,"title":["HIV-1 Vpr Enhances PPAR\u03b2\/\u03b4-Mediated Transcription, Increases PDK4 Expression, and Reduces PDC Activity"],"prefix":"10.1210","volume":"27","author":[{"given":"Shashi","family":"Shrivastav","sequence":"first","affiliation":[{"name":"Kidney Disease Section (S.S., K.O., H.L., Y.A., J.B.K.), National Institute of Diabetes and Digestive and Kidney Diseases"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liyan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Centre (L.Z., G.D.L.), Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Koji","family":"Okamoto","sequence":"additional","affiliation":[{"name":"Kidney Disease Section (S.S., K.O., H.L., Y.A., J.B.K.), National Institute of Diabetes and Digestive and Kidney Diseases"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hewang","family":"Lee","sequence":"additional","affiliation":[{"name":"Kidney Disease Section (S.S., K.O., H.L., Y.A., J.B.K.), National Institute of Diabetes and Digestive and Kidney Diseases"},{"name":"Division of Nephrology (H.L.), Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland 21201"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia","family":"Lagranha","sequence":"additional","affiliation":[{"name":"Laboratory of Cardiac Physiology (C.L.), National Heart Lung and Blood 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