1712-P: HIV-1 Vpr Couples Metabolic Inflexibility with White Adipose Tissue Thermogenesis

Abstract

The HIV accessory protein Vpr contributes to cardinal metabolic defects noted in persons living with HIV (PLWH), including accelerated lipolysis, impaired fatty acid oxidation, slowed fatty acid export, and steatohepatitis (Agarwal et al, Sci Trans Med 2017). PLWH also manifest “beiging” and markers of thermogenesis within some white adipose tissue (WAT) depots, but paradoxically these changes correlate with decreased insulin sensitivity and hyperlipidemia. We sought to determine whether Vpr activity affects thermogenesis and the dynamics of beiging in two Vpr mouse models. UCP1 expression was strongly increased in subcutaneous fat of Vpr mice and showed equivalent copy number in WAT biopsies from PLWH. Histology confirmed browning of subcutaneous but not visceral WAT in the Vpr mouse models. Adipocytes derived from these depots showed increased oxygen consumption rate in subcutaneous but not visceral fat cells, also strongly indicative of beiging. Measurements of energy balance indicated Vpr mice display metabolic inflexibility and cannot shift efficiently from carbohydrates to fat during day-night cycles. Furthermore, Vpr mice mice showed a marked inability to defend body temperature when exposed to 4oC for 6 hours. Thus HIV-1 Vpr disrupts metabolic efficiency coupled with maladaptive subcutaneous WAT beiging. These data suggest an expanded role for Vpr in the pathogenesis of HIV-associated metabolic disorders. Disclosure N. Agarwal: None. P. Saha: None. S.M. Hartig: None. A. Balasubramanyam: None. Funding National Institutes of Health (R21/R33AI116208)