Effects of transgenic expression of HIV-1 Vpr on lipid and energy metabolism in mice

Ashok Balasubramanyam, Harry Mersmann, Farook Jahoor, Terry M. Phillips, Rajagopal V. Sekhar, Ulrich Schubert, Baljinder Brar, Dinakar Iyer, E. O Brian Smith, Hideko Takahashi, Huiyan Lu, Peter Anderson, Tomoshige Kino, Peter Henklein, Jeffrey B. Kopp

Research output: Contribution to journalArticle

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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-γ 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.

Original languageEnglish
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume292
Issue number1
DOIs
Publication statusPublished - Jan 2007
Externally publishedYes

Fingerprint

Human Immunodeficiency Virus vpr Gene Products
vpr Gene Products
Lipid Metabolism
Energy Metabolism
HIV-1
Indinavir
High Fat Diet
Dexamethasone
Adipose Tissue
Liver
Lipids
White Adipose Tissue
Peroxisome Proliferator-Activated Receptors
Phosphoenolpyruvate
Wild Animals
Brown Adipose Tissue
Dietary Fats
Glucocorticoid Receptors
Capillary Electrophoresis
Body Composition

Keywords

  • Cholesterol
  • Energy expenditure
  • Fat oxidation
  • Glucose
  • Human immunodeficiency virus lipodystrophy
  • Triglycerides

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

Cite this

Balasubramanyam, A., Mersmann, H., Jahoor, F., Phillips, T. M., Sekhar, R. V., Schubert, U., ... Kopp, J. B. (2007). Effects of transgenic expression of HIV-1 Vpr on lipid and energy metabolism in mice. American Journal of Physiology - Endocrinology and Metabolism, 292(1). https://doi.org/10.1152/ajpendo.00163.2006

Effects of transgenic expression of HIV-1 Vpr on lipid and energy metabolism in mice. / Balasubramanyam, Ashok; Mersmann, Harry; Jahoor, Farook; Phillips, Terry M.; Sekhar, Rajagopal V.; Schubert, Ulrich; Brar, Baljinder; Iyer, Dinakar; Smith, E. O Brian; Takahashi, Hideko; Lu, Huiyan; Anderson, Peter; Kino, Tomoshige; Henklein, Peter; Kopp, Jeffrey B.

In: American Journal of Physiology - Endocrinology and Metabolism, Vol. 292, No. 1, 01.2007.

Research output: Contribution to journalArticle

Balasubramanyam, A, Mersmann, H, Jahoor, F, Phillips, TM, Sekhar, RV, Schubert, U, Brar, B, Iyer, D, Smith, EOB, Takahashi, H, Lu, H, Anderson, P, Kino, T, Henklein, P & Kopp, JB 2007, 'Effects of transgenic expression of HIV-1 Vpr on lipid and energy metabolism in mice', American Journal of Physiology - Endocrinology and Metabolism, vol. 292, no. 1. https://doi.org/10.1152/ajpendo.00163.2006
Balasubramanyam, Ashok ; Mersmann, Harry ; Jahoor, Farook ; Phillips, Terry M. ; Sekhar, Rajagopal V. ; Schubert, Ulrich ; Brar, Baljinder ; Iyer, Dinakar ; Smith, E. O Brian ; Takahashi, Hideko ; Lu, Huiyan ; Anderson, Peter ; Kino, Tomoshige ; Henklein, Peter ; Kopp, Jeffrey B. / Effects of transgenic expression of HIV-1 Vpr on lipid and energy metabolism in mice. In: American Journal of Physiology - Endocrinology and Metabolism. 2007 ; Vol. 292, No. 1.
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