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

Shin Wen,David L Williamson,Todd C Rideout,Kavita S Jadhav

doi:10.1155/2013/908048

Shin Wen, David L Williamson + Show 2 more

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https://doi.org/10.1155/2013/908048

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Abstract

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.

Highlights

Aerobic exercise is consistently associated with favorable shifts in blood triglycerides and HDL-C; data from intervention studies [1, 2] and numerous meta-analyses [3,4,5,6] support a less well-characterized and variable LDL-C lowering response to exercise training
The objective of this study was to examine the effects of aerobic exercise training in modulating proprotein convertase subtilisin/kexin type 9 (PCSK9) abundance and hepatic sterol regulation in a high-fat-fed C57BL/6 mouse compared with untrained control animals
Changes in body weight (BW) were independent of feed intake as no difference (P > 0.05) was observed between the LF, HF, and HF + EX groups (Table 2)

Summary

Introduction

Aerobic exercise is consistently associated with favorable shifts in blood triglycerides and HDL-C; data from intervention studies [1, 2] and numerous meta-analyses [3,4,5,6] support a less well-characterized and variable LDL-C lowering response to exercise training. Beyond LDL-C lowering, lipoprotein-profiling studies suggest that highintensity exercise training may modulate LDL particle number and size distribution patterns [7, 8]. Using a kinetic tracer approach, Ficker et al recently shed light on the potential mechanism of LDL-C lowering in response to exercise training. They reported increased fractional LDL clearance in both hypercholesterolemic and normolipidemic individuals following a 4-month exercise program consisting of stretching, cycling, and strength training exercises [9]. Function/distribution studies suggest that PCKS9 is synthesized and secreted predominately by the liver and initiates extracellular degradation of membrane-incorporated LDLr following direct binding [14], intracellular mechanisms may be involved

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