PMID- 30238979 OWN - NLM STAT- MEDLINE DCOM- 20200316 LR - 20200316 IS - 1097-4652 (Electronic) IS - 0021-9541 (Linking) VI - 234 IP - 4 DP - 2019 Apr TI - Exercise rescues the immune response fine-tuned impaired by peroxisome proliferator-activated receptors gamma deletion in macrophages. PG - 5241-5251 LID - 10.1002/jcp.27333 [doi] AB - 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. CI - (c) 2018 Wiley Periodicals, Inc. FAU - Silveira, Loreana Sanches AU - Silveira LS AUID- ORCID: 0000-0003-4429-0153 AD - Department of Physical Education, Exercise and Immunometabolism Research Group, Post-Graduation Program in Movement Sciences, Sao Paulo State University (UNESP), Sao Paulo, Brazil. AD - Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of Sao Paulo (USP), Sao Paulo, Brazil. FAU - Batatinha, Helena Angelica Pereira AU - Batatinha HAP AD - Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of Sao Paulo (USP), Sao Paulo, Brazil. FAU - Castoldi, Angela AU - Castoldi A AD - Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil. FAU - Camara, Niels Olsen Saraiva AU - Camara NOS AD - Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil. FAU - Festuccia, Willian T AU - Festuccia WT AD - Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil. FAU - Souza, Camila Oliveira AU - Souza CO AD - Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of Sao Paulo (USP), Sao Paulo, Brazil. FAU - Rosa Neto, Jose Cesar AU - Rosa Neto JC AD - Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of Sao Paulo (USP), Sao Paulo, Brazil. FAU - Lira, Fabio Santos AU - Lira FS AD - Department of Physical Education, Exercise and Immunometabolism Research Group, Post-Graduation Program in Movement Sciences, Sao Paulo State University (UNESP), Sao Paulo, Brazil. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180921 PL - United States TA - J Cell Physiol JT - Journal of cellular physiology JID - 0050222 RN - 0 (Adiponectin) RN - 0 (Adipoq protein, mouse) RN - 0 (Inflammation Mediators) RN - 0 (Lipids) RN - 0 (PPAR gamma) RN - 0 (Pparg protein, mouse) SB - IM MH - Adiponectin/blood MH - Adipose Tissue/metabolism MH - Animals MH - *Cell Plasticity MH - Cells, Cultured MH - *Energy Metabolism MH - Gene Deletion MH - Inflammation Mediators/*metabolism MH - Lipids/blood MH - Macrophages, Peritoneal/immunology/*metabolism MH - Male MH - Mice, Inbred C57BL MH - Mice, Knockout MH - PPAR gamma/*deficiency/genetics MH - Phenotype MH - Physical Conditioning, Animal/*methods MH - Physical Endurance MH - Time Factors OTO - NOTNLM OT - aerobic training OT - cytokines OT - energetic metabolism OT - transcriptional factor EDAT- 2018/09/22 06:00 MHDA- 2020/03/17 06:00 CRDT- 2018/09/22 06:00 PHST- 2018/03/13 00:00 [received] PHST- 2018/08/10 00:00 [accepted] PHST- 2018/09/22 06:00 [pubmed] PHST- 2020/03/17 06:00 [medline] PHST- 2018/09/22 06:00 [entrez] AID - 10.1002/jcp.27333 [doi] PST - ppublish SO - J Cell Physiol. 2019 Apr;234(4):5241-5251. doi: 10.1002/jcp.27333. Epub 2018 Sep 21.