FIGURE 5.

Metabolic stress and organelle dysfunction in obesity cardiomyopathy: Obesity leads to decreased myocardial glucose uptake and oxidation, increased fatty acid oxidation (FAO), and altered cardiomyocyte gene expression. Increased triglyceride accumulation and their products, such as ceramides and DAG, cause majority of lipotoxicity in hearts. Different metabolic pathways such as hexosamine and advanced glycation end-product (AGE) pathways have been identified as pro-oxidative processes and are usually elevated in uncorrected obesity. Autophagy activity in the heart declines with obesity, and its insufficiency is involved in the accumulation of reactive oxygen species (ROS) and the development of endoplasmic reticulum (ER) stress, leading to obesity-related cardiometabolic diseases. GLUT4, glucose transporter type 4; DAG, diacylglycerol; O-GlcNAc, β-linked N-acetylglucosamine; AGEs; advanced glycation end-products; FA, fatty acid; ROS, reactive oxygen species. Created with BioRender.com.