HIV-1 Viral Protein R Couples Metabolic Inflexibility With White Adipose Tissue Thermogenesis
Agarwal N, Iyer D, Saha P, Cox AR, Xia Y, Utay NS, Somasundaram A, Schubert U, Lake JE, Hartig SM, Balasubramanyam A (2021)
Publication Type: Journal article
Publication year: 2021
Journal
Book Volume: 70
Pages Range: 2014-2025
Journal Issue: 9
DOI: 10.2337/db20-0888
Abstract
Persons living with HIV (PLWH) manifest chronic disorders of brown and white adipose tissues that lead to diabetes and metabolic syndrome. The mechanisms that link viral factors to defective adipose tissue function and abnormal energy balance in PLWH remain incompletely understood. Here, we explored how the HIV accessory protein viral protein R (Vpr) contributes to adaptive thermogenesis in two mouse models and human adipose tissues. Uncoupling protein 1 (UCP1) gene expression was strongly increased in subcutaneous white adipose tissue (WAT) biopsy specimens from PLWH and in subcutaneous WAT of the Vpr mice, with nearly equivalent mRNA copy number. Histology and functional studies confirmed beige transformation in subcutaneous but not visceral WAT in the Vpr mice. Measurements of energy balance indicated Vpr mice displayed metabolic inflexibility and could not shift efficiently from carbohydrate to fat metabolism during day-night cycles. Furthermore, Vpr mice showed a marked inability to defend body temperature when exposed to 4 degrees C. Importantly, Vpr couples higher tissue catecholamine levels with UCP1 expression independent of beta -adrenergic receptors. Our data reveal surprising deficits of adaptive thermogenesis that drive metabolic inefficiency in HIV-1 Vpr mouse models, providing an expanded role for viral factors in the pathogenesis of metabolic disorders in PLWH.
Authors with CRIS profile
Involved external institutions
Houston Texas Medical Center
United States (USA) (US)
University of Texas Health Science Center at Houston (UTHealth)
United States (USA) (US)
University of Houston
United States (USA) (US)
United States (USA) (US)
University of Texas Health Science Center at Houston (UTHealth)
United States (USA) (US)
University of Houston
United States (USA) (US)
How to cite
APA:
Agarwal, N., Iyer, D., Saha, P., Cox, A.R., Xia, Y., Utay, N.S.,... Balasubramanyam, A. (2021). HIV-1 Viral Protein R Couples Metabolic Inflexibility With White Adipose Tissue Thermogenesis. Diabetes, 70(9), 2014-2025. https://dx.doi.org/10.2337/db20-0888
MLA:
Agarwal, Neeti, et al. "HIV-1 Viral Protein R Couples Metabolic Inflexibility With White Adipose Tissue Thermogenesis." Diabetes 70.9 (2021): 2014-2025.
BibTeX: Download