Endocrine Abstracts

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.