title: Effects of transgenic expression of HIV-1 Vpr on lipid and energy metabolism in mice.
abstract: HIV infection is associated with abnormal lipid metabolism, body fat redistribution, and altered energy expenditure. The pathogenesis of these complex abnormalities is unclear. Viral protein R (Vpr), an HIV-1 accessory protein, can regulate gene transcription mediated by the glucocorticoid receptor and peroxisome proliferator-activated receptor-gamma and affect mitochondrial function in vitro. To test the hypothesis that expression of Vpr in liver and adipocytes can alter lipid metabolism in vivo, we engineered mice to express Vpr under control of the phosphoenolpyruvate carboxykinase promoter in a tissue-specific and inducible manner and investigated the effects of dietary fat, indinavir, and dexamethasone on energy metabolism and body composition. The transgenic mice expressed Vpr mRNA in white and brown adipose tissues and liver and immunoaffinity capillary electrophoresis revealed that they had free Vpr protein in the plasma. Compared with wild-type (WT) animals, Vpr mice had lower plasma triglyceride levels after 6 wk (P < 0.05) but not after 10 wk of a high-fat diet and lower plasma cholesterol levels after 10 wk of high-fat diet (P < 0.05). Treatment with dexamethasone obviated group differences, whereas indinavir had no significant independent effect on lipids. In the fasted state, Vpr mice had a higher respiratory quotient than WT mice (P < 0.05). These data provide the first in vivo evidence that HIV-1 Vpr expressed at low levels in adipose tissues and liver can 1) circulate in the blood, 2) regulate lipid and fatty acid metabolism, and 3) alter fuel selection for oxidation in the fasted state.
authors.affiliation: Translational Metabolism Unit, Division of Diabetes, Endocrinology and Metabolism, BCM 700B, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA. ashokb@bcm.tmc.edu
authors.forename: Ashok
authors.initials: A
authors.lastname: Balasubramanyam
authors.forename: Harry
authors.initials: H
authors.lastname: Mersmann
authors.forename: Farook
authors.initials: F
authors.lastname: Jahoor
authors.forename: Terry M
authors.initials: TM
authors.lastname: Phillips
authors.forename: Rajagopal V
authors.initials: RV
authors.lastname: Sekhar
authors.forename: Ulrich
authors.initials: U
authors.lastname: Schubert
authors.forename: Baljinder
authors.initials: B
authors.lastname: Brar
authors.forename: Dinakar
authors.initials: D
authors.lastname: Iyer
authors.forename: E O'Brian
authors.initials: EO
authors.lastname: Smith
authors.forename: Hideko
authors.initials: H
authors.lastname: Takahashi
authors.forename: Huiyan
authors.initials: H
authors.lastname: Lu
authors.forename: Peter
authors.initials: P
authors.lastname: Anderson
authors.forename: Tomoshige
authors.initials: T
authors.lastname: Kino
authors.forename: Peter
authors.initials: P
authors.lastname: Henklein
authors.forename: Jeffrey B
authors.initials: JB
authors.lastname: Kopp
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D002151:Calorimetry; D004032:Diet; D004734:Energy Metabolism / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D016336:Gene Products, vpr / Q000097:blood / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D015497:HIV-1 / Q000235:genetics; D007668:Kidney / Q000378:metabolism; D050356:Lipid Metabolism / Q000235:genetics*; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D054325:vpr Gene Products, Human Immunodeficiency Virus
chemical_list: D016336:Gene Products, vpr; D054325:vpr Gene Products, Human Immunodeficiency Virus