This review highlights the critical role of nutrient-induced low-grade inflammation and subcellular component abnormalities in the pathogenesis and progression of metabolic cardiomyopathy.
Excessive feeding is associated with an increase in the incidence of chronic metabolic diseases, such as obesity, insulin resistance, and type 2 diabetes. Metabolic disturbance induces chronic low-grade inflammation in metabolically-important organs, such as the liver and adipose tissue. Many of the inflammatory signalling pathways are directly triggered by nutrients. The pro-inflammatory mediators in adipocytes and macrophages infiltrating adipose tissue promote both local and systemic pro-inflammatory status. Metabolic cardiomyopathy is a chronic metabolic disease characterized by structural and functional alterations and interstitial fibrosis without coronary artery disease or hypertension. In the early stage of metabolic cardiomyopathy, metabolic disturbance is not accompanied by substantial changes in myocardial structure and cardiac function. However, metabolic disturbance induces subcellular low-grade inflammation in the heart, and in turn, subcellular component abnormalities, such as oxidative stress, mitochondrial dysfunction, endoplasmic reticulum stress, and impaired calcium handling, leading to impaired myocardial relaxation. In the advanced stage, the vicious cycle of subcellular component abnormalities, inflammatory cell infiltration, and neurohumoral activation induces cardiomyocyte injury and death, and cardiac fibrosis, resulting in impairment of both diastolic and systolic functions. This review discusses some recent advances in understanding involvement of inflammation in metabolic cardiomyopathy.
Nishida et al. (Tue,) studied this question.