Publication Date
9-1-2021
Journal
Diabetes
DOI
10.2337/db20-0888
PMID
34233931
PMCID
PMC8576429
PubMedCentral® Posted Date
7-7-2021
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Keywords
Adipose Tissue, Brown, Adipose Tissue, White, Adult, Body Temperature, Energy Metabolism, Female, Humans, Middle Aged, Obesity, Thermogenesis, Uncoupling Protein 1, vpr Gene Products, Human Immunodeficiency Virus
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°C. Importantly, Vpr couples higher tissue catecholamine levels with UCP1 expression independent of β-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.
Included in
Biochemical Phenomena, Metabolism, and Nutrition Commons, Endocrine System Diseases Commons, Endocrinology, Diabetes, and Metabolism Commons