Low intensity exercise in the prevention of cardiac insulin resistance-related inflammation and disturbances in NOS and MMP-9 regulation in fructose-fed ovariectomised rats

Exercise is important nonpharmacological treatment for improvement of insulin sensitivity in menopause. However, its effect on menopausal cardiac insulin resistance is needing further research. We investigated protective effects of low intensity exercise on cardiac insulin signaling, inflammation, regulation of nitric oxide synthase (NOS) and matrix metalloproteinase 9 (MMP-9) in ovariectomised (OVX) Wistar rats, submitted to 10% fructose solution during 9 weeks. OVX rats were divided into control, sedentary fructose and exercise fructose group. Measurements of physical and biochemical characteristics were carried out to evaluate metabolic syndrome development. mRNA and protein levels and phosphorylation of cardiac insulin signaling molecules, endothelial and inducible NOS (eNOS and iNOS), p65 subunit of nuclear factor κB (NFκB), tumor necrosis factor α (TNF-α), suppressor of cytokine signalling 3 (SOCS3) and MMP-9 were analysed. Fructose increased insulin level, HOMA index and visceral adipose tissue weight, while low intensity exercise prevented insulin level and HOMA index increase. Fructose also decreased cardiac pAkt (Ser473), peNOS (Ser1177) and increased insulin receptor substrate 1 (IRS1) phosphorylation at Ser307, pNFκB (Ser276) and NFκB and MMP-9 content, without effects on iNOS, protein-tyrosine phosphatase 1B, TNF-α and SOCS3. Exercise prevented changes in pIRS1 (Ser307), pAkt (Ser473), peNOS (Ser1177), pNFκB (Ser276) and NFκB expression. In addition, exercise increased pIRS1 (Tyr632), pAkt (Thr308) and eNOS expression. The low intensity exercise prevented cardiac insulin signaling disarrangement in fructose-fed OVX rats and therefore eNOS dysfunction, as well as pro-inflammatory signaling activation, without effect on tissue remodeling, suggesting physical training as a tool for reduction of cardiovascular risk.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author