Cardiometabolic risk factors are associated with immune cell mitochondrial respiration in humans.

Modifiable cardiometabolic risk factors induce the release of pro-inflammatory cytokines and reactive oxygen species from circulating peripheral blood mononuclear cells (PBMCs) resulting in increased cardiovascular disease risk and compromised immune health. These changes may be driven by metabolic reprogramming of PBMCs resulting in impaired mitochondrial respiration; however, this has not been fully tested. We aimed to determine the independent associations between cardiometabolic risk factors, such as blood pressure, BMI, and plasma lipids with impaired mitochondrial respiration in PBMCs isolated from generally healthy individuals (n=21) across the adult lifespan (12 M/ 9 F; age: 56 ± 21 years; age-range: 22-78 year; blood pressure: 123 ± 16 / 72 ± 10 mmHg; low-density lipoprotein cholesterol, LDL-C: 111 ± 22 mg/dL; and high-density lipoprotein cholesterol, HDL-C: 62 ± 16 mg/dL). PBMCs were isolated from whole blood by density dependent centrifugation and used to assess mitochondrial function by respirometry. Primary outcomes included baseline and maximal oxygen consumption rate (OCR) which were subsequently used to determine spare respiratory capacity and OCR metabolic potential. After correcting for HDL-C, SBP, and age, LDL-C was negatively associated with maximal respiration (r=-0.61, P=0.0073), spare respiratory capacity (r=-0.65, P=0.0038) and OCR metabolic potential (r=-0.59, P=0.010), respectively. In addition, there was a strong, but non-significant positive association between HDL-C and maximal respiration (r=0.46, P=0.057) and spare respiratory capacity (r=0.43, P=0.075), after correcting for other covariates. These data suggest a link between blood cholesterol and mitochondrial health that may provide insight into how cardiometabolic risk factors contribute to impaired immune cell function.