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JNK signaling pathway in metabolic disorders: An emerging therapeutic target

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EUROPEAN JOURNAL OF PHARMACOLOGY
卷 901, 期 -, 页码 -

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ELSEVIER
DOI: 10.1016/j.ejphar.2021.174079

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Metabolic syndrome; Insulin resistance; Stress kinases; c-JunN-terminal kinase; Inflammation; Obesity

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Metabolic Syndrome is a multifactorial disease associated with increased risk of cardiovascular disorders, type 2 diabetes mellitus, fatty liver disease, etc., with stress kinase activation potentially playing a crucial role in regulating whole-body metabolism.
Metabolic Syndrome is a multifactorial disease associated with increased risk of cardiovascular disorders, type 2 diabetes mellitus, fatty liver disease, etc. Various stress stimuli such as reactive oxygen species, endoplasmic reticulum stress, mitochondrial dysfunction, increased cytokines, or free fatty acids are known to aggravate progressive development of hyperglycemia and hyperlipidemia. Although the exact mechanism contributing to altered metabolism is unclear. Evidence suggests stress kinase role to be a crucial one in metabolic syndrome. Stress kinase, c-jun N-terminal kinase activation (JNK) is involved in various metabolic manifestations including obesity, insulin resistance, fatty liver disease as well as cardiometabolic disorders. It emerged as a foremost mediator in regulating metabolism in the liver, skeletal muscle, adipose tissue as well as pancreatic beta cells. It has three isoforms each having a unique and tissue-specific role in altered metabolism. Current findings based on genetic manipulation or chemical inhibition studies identified JNK isoforms to play a central role in the regulation of whole-body metabolism, suggesting it to be a novel therapeutic target. Hence, it is imperative to elucidate its role in metabolic syndrome onset and progression. The purpose of this review is to elucidate in vitro and in vivo implications of JNK signaling along with the therapeutic strategy to inhibit specific isoform. Since metabolic syndrome is an array of diseases and complex pathway, carefully examining each tissue will be important for specific treatment strategies.

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