RESEARCH ARTICLE Effect of an acute moderate‐exercise session on metabolic and inflammatory profile of PPAR‐α knockout mice Loreana S. Silveira 1 | Gustavo D. Pimentel 2 | Camila O. Souza 3 | Luana A. Biondo 3 | Alexandre Abílio S. Teixeira 3 | Edson A. Lima 3 | Helena A. P. Batatinha 3 | José C. Rosa Neto 3 | Fábio S. Lira 1 1 Exercise and Immunometabolism Research Group, Department of Physical Education, Universidade Estadual Paulista, Presidente Prudente, SP, Brazil 2 Clinical and Sports Nutrition Research Laboratory (Labince), Nutrition Faculty (FANUT)—Federal University of Goiás (UFG), Goiânia, GO, Brazil 3 Immunometabolism Research Group, Institute of Biomedical Sciences, University of São Paulo (USP), São Paulo, SP, Brazil Correspondence Loreana Sanches Silveira, Exercise and Immunometabolism Research Group, Department of Physical Education, Universidade Estadual Paulista, UNESP, Rua Roberto Simonsen, 305, 19060‐900 Presidente Prudente, SP, Brazil. Email: loreana_loly@hotmail.com Funding information Fundação de Amparo à Pesquisa do Estado de São Paulo, Grant/Award Number: 2013/ 04765‐1, 2013/09367‐4, 2013/10861‐3, 2013/25310‐2 and 2014/01246‐6 Peroxisome proliferator‐activated receptors (PPARs) play a major role in metabolism and inflam- matory control. Exercise can modulate PPAR expression in skeletal muscle, adipose tissue, and macrophages. Little is known about the effects of PPAR‐α in metabolic profile and cytokine secretion after acute exercise in macrophages. In this context, the aim of this study was to under- stand the influence of PPAR‐α on exercise‐mediated immune metabolic parameters in peritoneal macrophages. Mice C57BL/6 (WT) and PPAR‐α knockout (KO) were examined in non‐exercising control (n = 4) or 24 hours after acute moderate exercise (n = 8). Metabolic parameters (glucose, non‐esterified fatty acids, total cholesterol [TC], and triacylglycerol [TG]) were assessed in serum. Cytokine concentrations (IL‐1β, IL‐6, IL‐10, TNF‐α, and MCP‐1) were measured from peritoneal macrophages cultured or not with LPS (2.5 μg/mL) and Rosiglitazone (1 μM). Exercised KO mice exhibited low glucose concentration and higher TC and TG in serum. At baseline, no difference in cytokine production between the genotypes was observed. However, IL‐1β was significantly higher in KO mice after LPS stimulus. IL‐6 and IL‐1β had increased concentrations in KO com- pared with WT, even after exercise. MCP‐1 was not restored in exercised KO LPS group. Rosiglitazone was not able to reduce proinflammatory cytokine production in KO mice at baseline level or associated with exercise. Acute exercise did not alter mRNA expression in WT mice. Con- clusion: PPAR‐α seems to be needed for metabolic glucose homeostasis and anti‐inflammatory effect of acute exercise. Its absence may induce over‐expression of pro‐inflammatory cytokines in LPS stimulus. Moreover, moderate exercise or PPAR‐γ agonist did not reverse this response. KEYWORDS acute exercise, cytokine, peritoneal macrophages, transcription factor 1 | INTRODUCTION Peroxisome proliferator‐activated receptors (PPARs) are members of the nuclear hormone receptor, which play a major role in metabolism. 1 There are 3 different isoforms from this group of transcriptional factors, PPAR‐α, PPAR‐β/δ, and PPAR‐γ, presenting functions such as fatty acid oxidation, lipogenesis, and regulation of energy homeosta- sis, respectively. 1 PPAR‐α is highly expressed in liver and can promote fatty acid oxidation by increasing genes responsible for intracellular fat acid transportation to peroxisome and mitochondria. 2 Furthermore, PPAR‐α is also found in macrophages and dendritic cells. 3 Most recently, studies have shown that PPARs are involved in inflammatory control by regulating the intensity, duration, and consequences of inflammatory responses. 2 PPAR‐α deficient mice present unbalanced ratio Th1/Th2, resulting in upregulation of pro‐ inflammatory Th1. 4 This fact may be explained by a downregulation of transcription factors related to Th1, such as T‐bet (T‐box expressed in T cells), with an increase of GATA‐3, an upregulator of Th2 cytokines. 1 Treatments with agonists of PPAR‐α have demon- strated reductions in plasma concentrations of proinflammatory cyto- kines (TNF‐α, IL‐1β, and IFN‐γ). 5 Additionally, it is well documented that chronic exercise, especially at moderate intensity, can improve insulin sensitivity and fat acid metabolism. Furthermore, the mecha- nisms that control these alterations are mediated by PPAR‐α in human skeletal muscle. 6 Received: 31 January 2017 Revised: 23 June 2017 Accepted: 17 September 2017 DOI: 10.1002/cbf.3308 Cell Biochem Funct. 2017;1–8. Copyright © 2017 John Wiley & Sons, Ltd. wileyonlinelibrary.com/journal/cbf 1