Effects of transgenic expression of HIV-1 Vpr on lipid and energy metabolism in mice.
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.
Balasubramanyam
Ashok
A
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
Mersmann
Harry
H
Jahoor
Farook
F
Phillips
Terry M
TM
Sekhar
Rajagopal V
RV
Schubert
Ulrich
U
Brar
Baljinder
B
Iyer
Dinakar
D
Smith
E O'Brian
EO
Takahashi
Hideko
H
Lu
Huiyan
H
Anderson
Peter
P
Kino
Tomoshige
T
Henklein
Peter
P
Kopp
Jeffrey B
JB
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
D016336:Gene Products, vpr; D054325:vpr Gene Products, Human Immunodeficiency Virus