Strenuous Exercise and Quercetin Supplementation Differentially Alter Lipid Metabolism in C57BL/6J Mice.

Abstract

Objective: While moderate exercise improves lipid profiles, strenuous activity can increase oxidative stress, highlighting the potential role of antioxidants. Quercetin, a polyphenol with both antioxidant and lipid-regulating effects, may counteract exercise-induced oxidative damage and influence cholesterol metabolism. This study investigates whether combining strenuous exercise with quercetin supplementation produces distinct effects on lipoprotein remodeling, offering insights into integrative approaches for reducing cardiovascular disease risk.

Methods: Forty C57BL/6 LDLr+/+ mice were randomly assigned to 4 groups (n=10): control with no exercise or quercetin (C), quercetin supplementation without exercise (Q), exercise without quercetin (E), and combined exercise with quercetin (EQ). All groups received a high-fat diet consisting of 42% fat and 1.5% cholesterol, formulated without added antioxidants. After 2 months, the mice were euthanized, and liver tissues were collected for gene expression analysis of ATP-binding cassette transporter A1 (ABCA1), proprotein convertase subtilisin/kexin type 9 (PCSK9), angiopoietin-like protein (ANGPTL) 3, ANGPTL4, peroxisome proliferator-activated receptor (PPAR) γ, apolipoprotein (APO) CIII, and APO A5 using quantitative real-time polymerase chain reaction.

Results: EQ produced the most pronounced alterations in metabolic markers and lipid-regulating genes. Both Q and EQ groups showed significantly elevated total cholesterol, high-density lipoprotein, triglycerides, and glucose compared with controls, while all treated groups exhibited reduced plasma lipase levels (p<0.05). EQ induced a significant downregulation of ABCA1 and PPARγ (p<0.05). PCSK9 messenger RNA expression rose in Q and EQ, reaching significance only in EQ, and adiponectin levels were significantly elevated in both E and EQ (p<0.05).

Conclusion: Hepatic lipoprotein expression was modulated by the combined effects of quercetin supplementation and exercise. The observed reductions in ABCA1 and PCSK9 expressions may reflect a feedback response to enhanced clearance of circulating cholesterol.