IGF-1 contributes to cardiovascular protection in obesity by upregulating Na+/K+-ATPase activity and modulating key signaling pathways in rats on a high-fat diet

This study examined the ability of insulin-like growth factor-1 (IGF-1) to improve the expression and function of cardiac sodium/potassium adenosine triphosphatase (Na⁺/K⁺-ATPase) and reduce heart hypertrophy in obese rats. Adult male Wistar rats received a standard diet or a high-fat (HF) diet for 12 weeks. A bolus injection of IGF-1 (50 μg/kg, i.p.) was administered to half of the HF rats 24 hours before euthanasia. IGF-1 treatment increased: the activity of Na⁺/K⁺-ATPase and expression of phosphorylated and total Na⁺/K⁺-ATPase α₁ subunit, the phosphorylation of IGF-1 receptor β /insulin receptor β at Tyr¹¹³¹/Tyr¹¹⁴⁶, insulin receptor substrate-1 (IRS-1) at Tyr¹²²², mammalian target of rapamycin (mTOR) at Ser²⁴⁸¹, protein kinase B (Akt) at Ser⁴⁷³ and the expression of type-2 angiotensin II (AngII) receptor (AT₂R). Conversely, IGF-1 reduced the levels of IRS-1 phosphorylated at Ser³⁰⁷, mTOR at Ser²⁴⁴⁸, ribosomal protein p70 S6 kinase (S6K) at Thr⁴²¹/Ser⁴²⁴, and the expression of type-1 Ang II receptor (AT₁R) in the heart, as well as the serum levels of Ang II in obese rats. IGF-1 treatment reduced cardiac mass and elevated mRNA expression of the α-myosin heavy chain (MHC), and the α/β MHC ratio in the hearts of obese rats. The results of this study suggest that the administration of IGF-1 to obese rats reduces the adverse effects of HF diet, potentially by lowering Ang II-mediated activation of mTOR/S6K and enhancing the IRS-1/Akt pathway, which promotes Na⁺/K⁺-ATPase activity in the heart and diminishes cardiac hypertrophy.