Chapter 1 - Overview of Autophagy and Cardiometabolic Syndrome

Abstract

The term cardiometabolic syndrome (CMS) refers to a constellation of cardiac metabolic and cardiovascular disease (CVD) risk factors including overweight/obesity, insulin resistance/hyperinsulinemia, hypertension, metabolic dyslipidemia, and microalbuminuria. Obesity is a central component of the CMS that is driven by consumption of high fat/refined carbohydrate diet and a sedentary lifestyle. Persons with the CMS have an increased risk for the development of type 2 diabetes mellitus, CVD, and chronic kidney disease. This increased risk is related to endothelial dysfunction, increased cardiovascular stiffness, impaired vascular and cardiac diastolic relaxation, and kidney disease. A pivotal component of CMS is systemic and tissue insulin resistance and one important link between insulin resistance and progression of CMS is autophagy. Autophagy is essential for effective maintenance of intracellular metabolic homeostasis and tissue quality control. However, this pathway is dysregulated in CMS and characterized by either inefficient autophagy or exaggerated/maladaptive autophagy and related to the development of insulin resistance. Both autophagy and insulin metabolic signaling are altered in CMS through interactions of excess dietary nutrients and inappropriate activation of renin-angiotensin-aldosterone system and inflammation. This overview addresses new insights into the interaction between abnormal autophagy and insulin resistance in the genesis and progression of the CMS, as well as potential strategies for drug targeting and lifestyle interventions to prevent and/or correct maladaptive autophagy and improve insulin sensitivity.