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Metabolic Activation

A Potential Mechanism for Exercise-Induced Phenotypic Switch in Macrophages

2660 May 29, 2

30 PM - 2

45 PM

Pence, Brandt D.; Woods, Jeffrey A. FACSM

Medicine & Science in Sports & Exercise: May 2015 - Volume 47 - Issue 5S - p 716
doi: 10.1249/
F-17 Free Communication/Slide - Immunology Friday, May 29, 2015, 1: 00 PM - 2: 45 PM Room: 30A

University of Illinois at Urbana-Champaign, Urbana, IL.

(No relationships reported)

PURPOSE: Exercise training is known to affect phenotype and function of immune cells, including macrophages. Exercise can reverse the pro-inflammatory phenotype of macrophages induced by physiological states such as obesity or aging. However, the mechanism by which exercise alters macrophage phenotype is unknown. Additionally, different metabolic activation patterns are known to differentially-regulate macrophage activation state. Specifically, oxidative metabolism in macrophages induces an anti-inflammatory phenotype. We sought to demonstrate in vitro a potential mechanism by which exercise may regulate macrophage phenotype.

METHODS: RAW 264.7 cells, a mouse macrophage cell line, were stimulated with 1 mM 5-Aminoimidazole-4-carboxamide ribonucleotide (AICAR) or vehicle for 24 hours, followed by isolation of messenger RNA from the cells for analysis of gene expression by quantitative real-time polymerase chain reaction (RT-PCR). Genes analyzed included markers of metabolic phenotype and alternative activation, including Ppargc1a, Sod1, Prkaa1, Hif1a, and Retnla.

RESULTS: Treatment with 1 mM AICAR for 24 hours increased expression of Ppargc1a (p=0.015) and Prkaa1 (p=0.025) in RAW 264.7 cells. These genes respectively control expression of proteins PGC-1α and the AMPK α1 subunit. AICAR treatment also upregulated Sod1 and Hif1a expression, although these were non-significant (p=0.096 and p=0.160, respectively). Retnla expression was too low to measure in this experiment.

CONCLUSIONS: Activation of AMPK leads to mitochondrial biogenesis and fatty acid oxidation. AICAR, an activator of AMPK, induced increased expression of genes related to these pathways in a macrophage cell line in vitro. Activation of AMPK signaling, whether directly or indirectly, is a potential mechanism by which exercise may influence macrophage phenotype.

© 2015 American College of Sports Medicine