The Role of Nerve Growth Factor in Diabetic Cardiomyopathy

Abstract

Obesity and type 2 diabetes mellitus (T2DM) are characterized by increased levels of circulating fatty acids, resulting in metabolic abnormalities in the heart. Emerging data has demonstrated that cardiac dysfunction, including diabetic cardiomyopathy (DCM), is linked to obesity and T2DM. Nerve growth factor (NGF), a neurotrophic factor, plays pro-survival and anti-apoptotic roles in cardiomyocytes. Therefore, the first study aimed to investigate the effects of NGF on myocardial insulin resistance, oxidative stress, apoptosis, and inflammation. In vitro study using H9c2 cell lines showed that high-glucose treatment induced myocardial insulin resistance. Combining palmitic acid and high-glucose treatment increased oxidative stress and activated apoptotic and inflammatory markers in cardiomyocytes. We also found that NGF administration prevented diabetic cardiomyopathy by inhibiting myocardial insulin resistance, oxidative stress, cardiac apoptosis, and inflammation via activation of the PI3K/Akt. The second part of the dissertation work aimed to clarify the role of mitochondrial dysfunction in the development of DCM and to examine the effects of NGF on mitochondrial dynamics, biogenesis, and mitophagy in obese and T2DM mouse models. Our western blot results showed no significant differences in mitochondrial dynamics and biogenesis proteins in all groups. However, cardiac mitophagy was suppressed in diabetic mice. Notably, intranasal NGF administration showed no effects on mitochondrial function. In summary, NGF administration prevented obesity- and T2DM-induced diabetic cardiomyopathy in vitro but not in vivo. These results suggest that the cardioprotective effects of NGF may depend on the delivery route of NGF. Further research is needed to clarify its effectiveness in diabetic heart using different NGF delivery routes.