HIV Increases Basal Metabolic Rate, Impairs Endothelial Function and Elevates Blood Pressure in Male and Female Mice
Authors: Kress Taylor C. , Nascimento Thiago Bruder , Kennard Simone , Wright Derrian , Faulkner Jessica L. , Belin de Chantemele Eric J. 
Published: April 2020

HIV is currently a major health concern with over 37 million individuals worldwide living with HIV and 1.7 million newly infected people in 2019. Thanks to the onset of combination antiretroviral therapy (cART) patients with HIV (PWH) live much longer but now exhibit accelerated development of metabolic and cardiovascular disease (CVD). Obesity currently affects 10% of the HIV population and clinical evidence indicates that 35% of PWH exhibit hypertension. However, the etiopathology of obesity and CVD remains ill‐defined in PWH. Notably, the respective contribution of viral infection and cART to cardiometabolic disorders remains unknown. The goal of this study is to take advantage of a transgenic mouse model (Tg26) that expresses 7 out of the 9 viral HIV proteins and mimics patients with a repressed virus, to decipher the contribution of viral infection to metabolic and cardiovascular dysfunction in male and female mice. Wild‐type (WT) and Tg26 mice were analyzed for body composition, energy expenditure (CLAMS cages), and glycemic impairment with glucose tolerance tests (GTT). Viral infection did not alter body weight in male and female Tg26 mice, but led to a significant reduction in both visceral (male: WT=0.049+/−0.008 vs. Tg26=0.030+/−0.006/female: WT=0.017+/−0.001 vs. Tg26=0.013+/−0.0004) and subcutaneous (male: WT=0.015+/−0.0007 vs. Tg26=0.011+/−0.0007/ female: WT=0.019+/−0.002 vs. Tg26=0.013+/−0.0007) adipose tissues in both in male and female Tg26 mice. Energy substrate utilization analysis via indirect calorimetry revealed a significant increase in the respiration exchange ratio in male Tg26 mice and a trend towards an increase in female mice (male: P<0.05/ female: P<0.1), indicating increased fat metabolism in male and female Tg26 mice. Similarly, energy expenditure tended to increase in male and was significantly increased in female Tg26 mice (male: P<0.1/ female: P<0.05). Measurement of glycemic impairment via GTT showed a trend towards impaired glycaemia only in male Tg26 mice (P<0.1). Cardiovascular dysfunction was studied via analysis of aorta reactivity using wire myography and blood pressure via radio‐telemetry. Our results indicated that both male and female Tg26 mice exhibit impaired endothelium dependent relaxation as reflected by a decrease in acetylcholine mediated relaxation with no impairment in smooth muscle cell relaxation (male: P<0.05/ female: P<0.05). Vascular constriction to phenylephrine and KCl was preserved in both male and female Tg26 mice. Blood pressure analysis of Tg26 mice via telemetry indicated that HIV increases blood pressure (male: WT=112.3+/−1.3 vs Tg26=121.9+/−4.0 mmHg/ female: WT=110.6+/−3.01/ Tg26=120.3+/−6.9 mmHg) in male and female Tg26 mice. Collectively, these data indicate that HIV viral infection increases energy expenditure and fat metabolism leading to decreased fat mass but also impairs endothelial function and elevate blood pressure, indicating that viral infection per se is a contributor to the metabolic and cardiovascular derangements exhibited by HIV patients.

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1R01HL130301‐01 and 1R01HL147639‐01A1 to EBC