Page 1 of 35 Articles in PresS. Am J Physiol Endocrinol Metab (August 1, 2006). doi:10.1152/ajpendo.00163.2006
1 Effects of transgenic expression of HIV-1 viral protein R (Vpr) on lipid and energy metabolism in mice Ashok Balasubramanyam1,3*, Harry Mersmann2*, Farook Jahoor2, Terry M. Phillips4, Rajagopal V. Sekhar1,3, Ulrich Schubert8, Baljinder Brar1, Dinakar Iyer1, E. O’Brian Smith2, Hideko Takahashi5, Huiyan Lu5, Peter Anderson7, Tomoshige Kino6, Peter Henklein9, Jeffrey B. Kopp5. 1
Translational Metabolism Unit, Division of Diabetes, Endocrinology, and Metabolism,
Department of Medicine, 2USDA/ARS-Children’s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX; 3Endocrine Service, Ben Taub General Hospital, Houston, TX; 4DEBPS, ORS, 5Kidney Disease Section, NIDDK and 6Reproductive Biology and Medicine Branch, NICHD, NIH, HHS, Bethesda, MD; 7University of Colorado Health Sciences Center, Denver, CO; 8Institute of Clinical and Molecular Virology, University of Erlangen-Nürnberg, Germany; 9Institute of Biochemistry, Humboldt University, D-10115 Berlin, Germany. *These two authors contributed equally to this work. Correspondence / Reprint Requests: Ashok Balasubramanyam, M.D., Translational Metabolism Unit, Division of Diabetes, Endocrinology and Metabolism, BCM 700B, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030 Ph: 713-798-8654; Fax: 713-798-3810; E-mail:
[email protected] Running Head: Lipid metabolism in Vpr transgenic mice
1 Copyright © 2006 by the American Physiological Society.
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2 ABSTRACT HIV infection is associated with abnormal lipid metabolism, body fat redistribution and altered energy expenditure. The pathogenesis of these complex abnormalities is unclear. Vpr, a HIV-1 accessory protein, can regulate gene transcription mediated by the glucocorticoid receptor and peroxisome proliferator activator receptor- , 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 to wild-type (WT) animals, Vpr mice had lower plasma triglyceride levels after 6 weeks (P
