Unmasking the janus faces of autophagy in obesity‐associated insulin resistance and cardiac dysfunction

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Abstract
1. Autophagy is an intracellular, lysosomal‐dependent process involved in the turnover of long‐lived proteins, damaged organelles and other subcellular structures. The autophagic process is known to play an essential role in the maintenance of cellular homeostasis. Results from recent studies also indicate an important role for the autophagic process in the pathogenesis of human diseases, including cancer, cardiovascular diseases, obesity, diabetes mellitus and ageing. 2. Because of the pivotal role of autophagy in the regulation of adipogenesis, obesity and insulin sensitization, research efforts have focused on elucidating the role of autophagy in metabolic syndrome. Mammalian target of rapamycin (mTOR) is a key regulator of cell growth and is characterized by a complex signalling mechanism that affects protein synthesis and autophagy. Results from experimental and clinical studies reveal some interesting, but conflicting, findings regarding the mTOR signalling pathway and autophagy in adipocytes in metabolic syndrome. 3. Although the pivotal role of autophagy in obesity and other metabolic diseases has been established, its involvement in obesity‐induced cardiac dysfunction remains unknown, as do the upstream signalling regulators of autophagy. The present minireview discusses the molecular mechanisms of autophagy in the regulation of cardiac function in overweight and obesity. Further studies using appropriate models are needed to better unravel the complex intracellular mechanisms involved in the regulation of autophagy in obesity‐induced cardiac dysfunction.

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