Since obesity is one of the main factors in the development of insulin resistance (IR) and is also associated with increased oxidative stress (OxS) rate, this study aims to review the published literature to collate and provide a comprehensive summary of the studies related to the status of the OxS in the pathogenesis of obesity and related IR. OxS represents an imbalance between the production of reactive oxygen and nitrogen species (RONS) and the capacity of the antioxidant defense system (AOS) to neutralize RONS. A steady-state of RONS level is maintained through endogenous enzymatic and non-enzymatic AOS components. Three crucial enzymes, which suppress the formation of free radicals, are superoxide dismutases, catalases, and glutathione peroxidases. The second line of AOS includes non-enzymatic components such as vitamins C and E, coenzyme Q, and glutathione which neutralizes free radicals by donating electrons to RONS. Emerging evidence suggests that high RONS levels contribute to the progression of OxS in obesity by activating inflammatory pathways and thus leading to the development of pathological states, including IR. In addition, decreased level of AOS components in obesity increases the susceptibility to oxidative tissue damage and further progression of its comorbidities. Increased OxS in accumulated adipose tissue should be an imperative target for developing new therapies in obesity-related IR.

Aim: Obesity is associated with activation of mammalian target of rapamycin (mTOR)/ ribosomal S6 kinase (S6K) signaling pathway that promotes cardiac hypertrophy, insulin resistance, endothelial dysfunction and oxidative stress. Although activation of mTOR/S6K has a harmful effect, simultaneously it represents adaptive metabolic response that protects cells from excessive nutrient intake. Insulin like growth factor-1 (IGF1) exerts pleiotropic action on heart promoting vasorelaxation, antiinflammatory, antiatherogenic and antioxidant activity. Aim of this study was to evaluate how IGF1 treatment influences mTOR/S6K signaling pathway and SOD 1 expression in heart of obese rats. Methods: Male Wistar rats were fed with standard laboratory diet or high fat (HF) diet (42% of fat) for 12 weeks and then half of all animals were treated intraperitoneally with one dose of IGF1 (50 μg/kg). After 24 h of treatment the animals were sacrificed and hearts excised. The expression of SOD 1 protein and phosphorylation and expression of mTOR and p70 S6K proteins were measured in rat heart lysates by Western blot method. Results: Decreased level of SOD1 protein was observed in hearts of normally fed rats treated with IGF1 (P<0.01) and obese rats (P<0.001), while it was increased in IGF1 treated obese rats. The activation of cardiac mTOR was increased in normally fed IGF1 treated rats (P<0.001) and obese rats (P<0.05), while it was decreased in IGF1 treated obese rats (P<0.01). The results also show that activation of p70 S6K was increased in heart of normally fed rats treated with IGF1 (P<0.01) and obese rats (P<0.05), while it was decreased in IGF1 treated obese rats (P<0.05). Conclusion: Results suggest that in heart of obese rats, IGF1 mitigates detrimental effects of obesity by increasing expression of SOD 1 protein, probably through mechanism that involves downregulation of mTOR/p70 S6K signaling pathway.