Role of autophagy in metabolic syndrome-associated heart disease

Abstract

Metabolic syndrome (MetS) is a constellation of multiple metabolic risk factors including abdominal obesity, glucose intolerance, insulin resistance, dyslipidemia and hypertension. Over the past decades, the prevalence of metabolic syndrome has increased dramatically, imposing a devastating, pandemic health threat. More importantly, individuals with metabolic syndrome are at an increased risk of diabetes mellitus and overall cardiovascular diseases. One of the common comorbidities of metabolic syndrome is heart anomalies leading to the loss of cardiomyocytes, cardiac dysfunction and ultimately heart failure. Up-to-date, a plethora cell signaling pathways have been postulated for the pathogenesis of cardiac complications in obesity including lipotoxicity, inflammation, oxidative stress, apoptosis and sympathetic overactivation although the precise mechanism of action underscoring obesity-associated heart dysfunction remains elusive. Recent evidence has indicated a potential role of protein quality control in components of metabolic syndrome. Within the protein quality control system, the autophagy-lysosome pathway is an evolutionarily conserved pathway responsible for bulk degradation of large intracellular organelles and protein aggregates. Autophagy has been demonstrated to play an indispensible role in the maintenance of cardiac geometry and function under both physiological and pathological conditions. Accumulating studies have demonstrated that autophagy plays a pivotal role in the etiology of cardiac anomalies under obesity and metabolic syndrome. In this mini review, we will discuss on how autophagy is involved in the regulation of cardiac function in obesity and metabolic syndrome.

Dietary potassium regulates vascular calcification and arterial stiffness

“…Autophagy is an evolutionarily conserved, complex cellular pathway that delivers cytoplasmic contents for degradation in lysosomes (64,65). Autophagosome-like structures are documented in VSMCs in atherosclerotic lesions in human and animal models (66).…”

Tetrahydroxystilbene Glycoside Improves Microvascular Endothelial Dysfunction and Ameliorates Obesity-Associated Hypertension in Obese ZDF Rats Via Inhibition of Endothelial Autophagy

“…Accumulating evidence has demonstrated the pivotal role of autophagy in the metabolic syndrome and its complications [36]. Omental adipose tissues from obese patients with type-2 diabetes mellitus have shown a reduction in expression of mammalian target of rapamycin complex-1 with a simultaneous increase in autophagy and impaired mitochondria [37].…”

“…Autophagy is indispensable for cellular homeostasis and organism longevity, and it is in balance with metabolic cycles [14]. Several studies have illustrated that autophagy has a pivotal role in the pathogenesis of myocardial lesions in obesity and the metabolic syndrome [15]. High-fat diet (HFD)-induced obesity disrupts maturation of myocardial autophagosomes.…”

Metabolic syndrome is associated with different clinical outcome after cardiac resynchronization therapy in patients with ischemic and non-ischemic cardiomyopathy

“…Obesity leads to the loss of cardiomyocytes, cardiac dysfunction and ultimately HF [32]. An unexpected finding of our analysis is that patients with obesity without metabolic components had better reduction in mortality and HF/death when having ischemic cardiomyopathy despite similar up front risk.…”