Division of Diabetes, Endocrinology, and Metabolism, Baylor College of Medicine, Houston, Texas, USA.
Atherosclerosis and Lipoprotein Research, Baylor College of Medicine, Houston, Texas, USA.
Physiol Rep. 2022 May;10(9):e15293. doi: 10.14814/phy2.15293.
Plasma biomarkers that reflect energy balance disorders in people living with HIV (PLWH) remain limited. Growth differentiation factor 15 (GDF15) abundance in plasma of mice and humans induces negative energy balance but also becomes highly elevated in obesity and other metabolic diseases. We sought to compare plasma GDF15 levels in PLWH and HIV-negative persons and mouse models expressing the HIV accessory protein Vpr (that recapitulate HIV-associated metabolic disorders) and determine their relationship to metabolic parameters. We measured liver Gdf15 mRNA levels and plasma GDF15 levels in male Vpr mice and littermate controls. In parallel, we analyzed plasma GDF15 levels in 18 male PLWH on stable, long-term antiretroviral therapy and 13 HIV-negative men (6 healthy controls and 7 with metabolic syndrome). Plasma GDF15 levels were correlated with anthropometric and immune cell parameters in humans. Gene expression analysis of Vpr mouse liver demonstrated elevated Gdf15 mRNA. Plasma GDF15 levels were also higher in Vpr mouse models. Levels of plasma GDF15 in PLWH were greater than in both HIV-negative groups and correlated positively with the CD4/CD8 T cell ratio in PLWH. Plasma GDF15 levels correlated positively with age in the HIV-negative subjects but not in PLWH. Since GDF15 levels predict fatty liver disease and energy balance disorders, further studies are warranted to determine the effect of GDF15 in mediating the metabolic disturbances that occur in Vpr mice and PLWH.
血浆生物标志物可反映人类免疫缺陷病毒（HIV）感染者（PLWH）的能量平衡紊乱，但目前此类标志物十分有限。生长分化因子 15（GDF15）在人和小鼠的血浆中含量丰富，可引起负性能量平衡，但在肥胖症和其他代谢性疾病中含量也会显著升高。我们试图比较 HIV 阴性者和表达 HIV 辅助蛋白 Vpr 的 PLWH 及小鼠模型（可再现与 HIV 相关的代谢紊乱）的血浆 GDF15 水平，并确定其与代谢参数的关系。我们检测了雄性 Vpr 小鼠及其同窝对照的肝脏 Gdf15mRNA 水平和血浆 GDF15 水平。同时，我们分析了 18 名接受长期稳定抗逆转录病毒治疗的男性 PLWH 和 13 名 HIV 阴性男性（6 名健康对照者和 7 名代谢综合征患者）的血浆 GDF15 水平。人类的血浆 GDF15 水平与人体测量和免疫细胞参数相关。Vpr 小鼠肝脏的基因表达分析显示 Gdf15mRNA 水平升高。Vpr 小鼠模型的血浆 GDF15 水平也较高。PLWH 的血浆 GDF15 水平高于两个 HIV 阴性组，与 PLWH 的 CD4/CD8T 细胞比值呈正相关。在 HIV 阴性者中，血浆 GDF15 水平与年龄呈正相关，但在 PLWH 中则无此相关性。由于 GDF15 水平可预测脂肪肝和能量平衡紊乱，因此需要进一步研究以确定 GDF15 在介导 Vpr 小鼠和 PLWH 中发生的代谢紊乱中的作用。
