Aerobic exercise training enhances the in vivo cholesterol trafficking from macrophages to the liver independently of changes in the expression of genes involved in lipid flux in macrophages and aorta

Abstract

BackgroundRegular exercise prevents and regresses atherosclerosis by improving lipid metabolism and antioxidant defenses. Exercise ameliorates the reverse cholesterol transport (RCT), an antiatherogenic system that drives cholesterol from arterial macrophages to the liver for excretion into bile and feces. In this study we analyzed the role of aerobic exercise on the in vivo RCT and expression of genes and proteins involved in lipid flux and inflammation in peritoneal macrophages, aortic arch and liver from wild type mice.MethodsTwelve-week-old male mice were divided into sedentary and trained groups. Exercise training was performed in a treadmill (15 m/min, 30 min/day, 5 days/week). Plasma lipids were determined by enzymatic methods and lipoprotein profile by fast protein liquid chromatography. After intraperitoneal injection of J774-macrophages the RCT was assessed by measuring the recovery of 3H-cholesterol in plasma, feces and liver. The expression of liver receptors was determined by immunoblot, macrophages and aortic mRNAs by qRT-PCR. 14C-cholesterol efflux mediated by apo A-I and HDL2 and the uptake of 3H-cholesteryl oleoyl ether (3H-COE)-acetylated-LDL were determined in macrophages isolated from sedentary and trained animals 48 h after the last exercise session.ResultsBody weight, plasma lipids, lipoprotein profile, glucose and blood pressure were not modified by exercise training. A greater amount of 3H-cholesterol was recovered in plasma (24 h and 48 h) and liver (48 h) from trained animals in comparison to sedentary. No difference was found in 3H-cholesterol excreted in feces between trained and sedentary mice. The hepatic expression of scavenger receptor class B type I (SR-BI) and LDL receptor (B-E) was enhanced by exercise. We observed 2.8 and 1.7 fold rise, respectively, in LXR and Cyp7a mRNA in the liver of trained as compared to sedentary mice. Macrophage and aortic expression of genes involved in lipid efflux was not systematically changed by physical exercise. In agreement, 14C-cholestrol efflux and uptake of 3H-COE-acetylated-LDL by macrophages was similar between sedentary and trained animals.ConclusionAerobic exercise in vivo accelerates the traffic of cholesterol from macrophages to the liver contributing to prevention and regression of atherosclerosis, independently of changes in macrophage and aorta gene expression.

Expression Profiles of Cytochrome P450s Following Swimming Exercise in Aging Rats

“…Regular aerobic exercise increases Cyp7a1 levels, increases the effective control of cholesterol in the liver, and prevents atherosclerosis by increasing HDL levels. 42 PXR plays an important role in the regulation of CYP3A4, a major DME in humans. 43 In a previous study, swimming exercise for 8 weeks was found to increase mRNA and protein expression of PPAR in elderly mice, and the expression of 3-hydroxyacyl CoA dehydrogenase and carnitine palmitoyl transferase-I, target genes of PPAR, was also increased in the heart.…”

Atherogenesis: hyperhomocysteinemia interactions with LDL, macrophage function, paraoxonase 1, and exercise

“…All of these improvements correlate with reduction in macrophages in the plaques, implying that exercise can prevent foam cell formation and reduced macrophage motility, the hallmarks of atherogenesis. Support for such a hypothesis comes from another recent report that indicated an exercise‐mediated enhancement in reverse cholesterol transport …”

“…Support for such a hypothesis comes from another recent report that indicated an exercise-mediated enhancement in reverse cholesterol transport. 187 Exercise significantly reduced triglyceride levels, but its effects on cholesterol content vary. 179 Lowintensity exercise decreases total cholesterol content, but increases OxLDL, HDL, and LXR␣ (most likely through PPAR␥ ) levels, the latter two being involved with cholesterol efflux and thus having low propensity for atherosclerosis.…”

“…Acute exercise induces an increase in oxidative stress (OxLDL) only in untreated mild hypertensive patients with atherogenic lipid profiles . Recently, aerobic exercise was shown to enhance cholesterol transit from macrophages to the liver (reverse cholesterol transport), potentially conferring prevention and regression of atherosclerosis . Other studies also indicated that exercise can potentially enhance macrophage cholesterol efflux through upregulation of ABCA1 levels .…”

“…189 Recently, aerobic exercise was shown to enhance cholesterol transit from macrophages to the liver (reverse cholesterol transport), potentially conferring prevention and regression of atherosclerosis. 187 Other studies also indicated that exercise can potentially enhance macrophage cholesterol efflux through upregulation of ABCA1 levels. 190 Together, these results suggest that regular exercise of low intensity but not acute exercise confers benefits in countering atherogenesis.…”