Diabetic cardiomyopathy (DCM), a metabolic disorder, is one of the leading causes of mortality around the world and its pathogenesis involves cardiac
inflammation and altered metabolic profile. Altered
fatty acid metabolism during DCM can cause macrophage polarization in which inflammatory M1 phenotype dominates over the anti-inflammatory M2 phenotype. Hence, it is essential to identify a specific target, which could revert the metabolic profile and thereby reducing the M1 macrophage polarization. 14-3-3η
protein has several cellular protective functions especially in the heart as plenty of reports available in various animal models of
heart failure including
diabetes mellitus. However, its role in the cardiac
fatty acid metabolism and macrophage polarization remains unidentified. The present study has been designed to delineate the effect of cardiospecific dominant negative mutation of 14-3-3η
protein (DN14-3-3) on various lipid metabolism related marker
proteins expressions and cardiac macrophage phenotype in high fat diet (HFD) fed mice. Feeding HFD for 12 weeks has produced significant increase in
body weight in the DN14-3-3 (TG) mice than C57BL6/J (WT) mice. Western blotting and immunohistochemical staining analysis of the heart tissue has revealed an increase in the expression of markers of cardiac
fatty acid synthesis related
proteins in addition to the reduced expression of
fatty acid oxidation related
proteins in TG mice fed HFD than WT mice fed HFD. Furthermore, the M1 macrophage marker
proteins were increasingly expressed while M2 markers expressions were reduced in the hearts of TG mice fed HFD. In conclusion, our current study has identified that there is a definite role for the 14-3-3η
protein against the pathogenesis of
heart failure via regulation of cardiac
fatty acid metabolism and macrophage polarization.