Treadmill Exercise Training Modulates Hepatic Cholesterol Metabolism and Circulating PCSK9 Concentration in High-Fat-Fed Mice

Abstract EN

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a novel biomarker of LDL clearance and a therapeutic target of cardiovascular disease.

We examined the effects of aerobic exercise training in modulating PCSK9 abundance and hepatic sterol regulation in high-fat-fed C57BL/6 mice.

Mice (n=8) were assigned to a low-fat (LF), high-fat (HF), or an HF with exercise (HF + EX) group for 8 weeks.

The HF + EX group was progressively trained 5 days/week on a motorized treadmill.

The HF + EX group was protected against body weight (BW) gain and diet-induced dyslipidemia compared with the HF group.

The HF + EX group demonstrated an increase in hepatic PCSK9 mRNA (1.9-fold of HF control, P<0.05) and a reduction in plasma PCSK9 (14%) compared with the HF group.

Compared with HF mice, HF + EX mice demonstrated reduced hepatic cholesterol (14%) and increased (P<0.05) nuclear SREBP2 protein (1.8-fold of HF group) and LDLr mRNA (1.4-fold of HF group).

Plasma PCSK9 concentrations correlated positively with plasma non-HDL-C (P=0.01, r=0.84).

Results suggest that treadmill exercise reduces non-HDL cholesterol and differentially modulates hepatic and blood PCSK9 abundance in HF-fed C57BL/6 mice.