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) biopsies from PLWH and in
subcutaneous WAT of the Vpr mice, with near-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<sup>o</sup>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.
HIV-1 Viral Protein R Couples Metabolic inflexibility with White Adipose Tissue Thermogenesis