Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Emerging studies have demonstrated that microRNAs (miRs) participate in the development of multiple metabolic complications including cardiovascular diseases. Among them, circulating level of liver-secreted miR-122 was closely correlated with several consequence of heart diseases in clinical studies, and overexpression of miR-122 impaired cardiomyocyte function. However, it was unknown whether miR-122 could regulate cardiac biology in obesity. Therefore, present study was to disclose the role of miR-122 in cardiac metabolic disorders and potential molecular mechanisms. Through utilizing clinical samples and high fat diet-fed mice, we investigated the physiological roles of miR-122 in obesity-related cardiomyopathy. Besides, present study explored the mitochondrial function under exosomal miR-122 stimulation in mouse primary cardiomyocytes. In clinical samples and obese mice, the circulating level of exosomal miR-122 was positively correlated with cardiac dysfunctional parameters, including reduction in ejection fraction (EF) and increased levels of NT-proBNP. Human plasma exosomes transported miR-122 into mouse primary cardiomyocytes, and impaired mitochondrial ATP production and oxygen consumption, whereas miR-122 sponge improved these inhibitory effects. In dietary-induced mice, increased hepatic and circulating exosomal miR-122 deteriorated cardiac structure and functional index, and inhibited mitochondrial function. Liver-specific blockage of miR-122 attenuated abnormal cardiac remodeling. Mechanistically, miR-122 directly bound and suppressed mitochondrial protein ADP-ribosylation factor-like 2 (Arl-2) in vitro and in vivo Knockdown of Arl-2 abolished the mitochondrial benefits of miR-122 sponge in exosome-treated mouse primary cardiomyocytes.In conclusions, our present study firstly showed that liver-secreted exosomal miR-122 played a critical role in the development of metabolic cardiomyopathy, and miR-122/mitochondrial Arl-2 signaling affected cardiac energy homeostasis.
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PMID:Exosomal microRNA-122 mediates obesity-related cardiomyopathy through suppressing mitochondrial ADP-ribosylation factor-like 2. 3143 96