613-P: Preventive Effect of Sulforaphane on Type 2 Diabetes-Induced Diabetic Cardiomyopathy via AMPK-Mediated Activation of Glucose/Lipid Metabolism and Nrf2 Function

Dyslipidemia has been shown to play a crucial role in the development of diabetic cardiomyopathy (DCM) in type 2 diabetes (T2D). AMP-activated protein kinase (AMPK), particularly α2 isoform can improve energy metabolism in cardiomyopathy. Sulforaphane (SFN), a natural isothiocyanate in vegetables, is important in cardiac protection from diabetes. We investigated whether SFN can protect heart from T2D damage, which is mediated by AMPKα2 via improving energy metabolism and activating Nrf2-mediated anti-oxidative pathways. AMPKα2 knockout (AMPKα2-KO) mice and their wild type (WT, C57BL/6J) mice were fed high-fat diet (HFD) for 3 months to induce insulin resistance, and then intraperitoneal injection of streptozotocin to induce hyperglycemia as T2D model. Age-matched mice were fed with normal diet (ND) without streptozotocin as control. T2D and control mice were treated with or without SFN for 3 months (3m) and then stop SFN treatment, remained feeding either ND or HFD for additional three months (6m). Echocardiography were performed before sacrifice both in 3m and 6m group. SFN treatment improved cardiac remodeling and dysfunction induced by T2D both in 3m and 6m group. The cardiac pathogenic changes induced by T2D, including fibrosis, lipotoxicity, inflammation, oxidative stress/damage along with suppression of AMPK signaling pathways was prevented by SFN in WT diabetic mice, as evidenced by down-regulating FN, TGF-β PAI-1, TNF-α, SCD-1and up-regulating CPT1-B, PPARα, Nrf2. The cardiac protection by SFN for 3 months from T2D could last till 6 months. AMPKα2-KO mice are also susceptible to T2D-induced cardiomyopathy; however, the protective effect of SFN on the heart from diabetes was lost in diabetic AMPKα2-KO mice. These results suggest that SFN treatment can attenuate cardiac damage induced by T2D both in the 3m and 6m group, and AMPKα2 plays the pivotal role in the SNF-mediated cardiac protection. Disclosure Y. Sun: None. L. Cai: None. Z. Li: None. Funding American Diabetes Association (1-18-IBS-082 to L.C.)