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Publication : Exercise rescues the immune response fine-tuned impaired by peroxisome proliferator-activated receptors γ deletion in macrophages.

First Author  Silveira LS Year  2019
Journal  J Cell Physiol Volume  234
Issue  4 Pages  5241-5251
PubMed ID  30238979 Mgi Jnum  J:294475
Mgi Id  MGI:6456494 Doi  10.1002/jcp.27333
Citation  Silveira LS, et al. (2019) Exercise rescues the immune response fine-tuned impaired by peroxisome proliferator-activated receptors gamma deletion in macrophages. J Cell Physiol 234(4):5241-5251
abstractText  BACKGROUND: Exercise is a powerful tool for prevention and treatment of many conditions related to the cardiovascular system and also chronic low-grade inflammation. Peroxisome proliferator-activated receptors gamma (PPARgamma) exerts an import role on the regulation of metabolic profile and subsequent inflammatory response, especially in macrophages. PURPOSE: To investigate the effects of 8-week moderate-exercise training on metabolic and inflammatory parameters in mice with PPARgamma deficiency in myeloid cells. METHODS: Twelve-week old mice bearing PPARgamma deletion exclusively in myeloid cells (PPARgammalox/lox Lys Cre (-/+) , knockout [KO]) and littermate controls (PPARgammalox/lox Lys Cre (-/-) , wild type [WT]) were submitted to 8-week exercise training (treadmill running at moderate intensity, 5 days/week). Animals were evaluated for food intake, glucose homeostasis, serum metabolites, adipose tissue and peritoneal macrophage inflammation, and basal and stimulated cytokine secretion. RESULTS: Exercise protocol did not improve glucose metabolism or adiponectin concentrations in serum of KO mice. Moreover, the absence of PPARgamma in macrophages exacerbated the proinflammatory profile in sedentary mice. Peritoneal cultured cells had higher tumor necrosis factor-alpha (TNF-alpha) secretion in nonstimulated and lipopolysaccharide (LPS)-stimulated conditions and higher Toll-4 receptor (TLR4) gene expression under LPS stimulus. Trained mice showed reduced TNF-alpha content in adipose tissue independently of the genotype. M2 polarization ability was impaired in KO peritoneal macrophages after exercise training, while adipose tissue-associated macrophages did not present any effect by PPARgamma ablation. CONCLUSION: Overall, PPARgamma seems necessary to maintain macrophages appropriate response to inflammatory stimulus and macrophage polarization, affecting also whole body lipid metabolism and adiponectin profile. Exercise training showed as an efficient mechanism to restore the immune response impaired by PPARgamma deletion in macrophages.
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