“Walking, PPARs, and their Regulated Genes”

An important mechanism by which physical activity reduces the risk of cardiovascular disease is through regulating plasma lipids. The ligand-dependant nuclear transcription factors Peroxisome Proliferator Activated Receptors α and γ (PPARα and γ) are important lipid sensors and regulators of inflammation with certain PPAR ligands having atheroprotective properties. In this study we investigated whether low-intensity exercise modulates the gene expression of PPARγ and α and also two of their regulated genes involved in lipid metabolism.

PURPOSE: To determine whether walking modulates gene expression of PPARγ and PPARα and of the PPARγ regulated gene CD14 and the PPARα regulated gene, Acyl-CoA oxidase.

METHODS: 34 sedentary adults, mean age 45.6±11.1 years, participated in an 8-week low-intensity exercise programme consisting of walking 10,000 steps, 3 times/week. Subjects were randomly allocated to either an exercise group or sedentary control group. After blood collection, mRNA extracted from leukocytes and gene expressions estimated by Real-Time PCR.

RESULTS: No changes in anthropometric data in the exercise or control participants were observed after the exercise programme. There was also no change in the dietary intake in either group pre-to post exercise. A significant increase in leukocyte mRNA expression for PPARγ (4 weeks: 1.8±0.9 fold; 8 weeks: 4.3±1.9 fold) was observed. The PPARγ regulated gene CD14, a lipid sensor, was significantly up-regulated post exercise (4 weeks: 1.8±0.2 fold; 8 weeks: 2.1±0.4 fold). A significant increase in gene expression was also observed for PPARα (4 weeks: 1.7±0.4). However, the mRNA of the PPARα regulated gene Acyl-CoA Oxidase, involved in fatty acid metabolism was not significantly altered after adherence to the exercise program.

CONCLUSION: An 8-week low-intensity exercise programme significantly increases gene expression of both PPARγ and PPARα. Increase in gene expression of these transcription factors has been shown to be associated with their activity. However, the increase in gene expression of these transcription factors is associated only with an increase in gene expression of a PPARγ regulated gene. This study suggests that the beneficial effects of low-intensity exercise are mediated mainly through PPARγ in leukocytes.