Dataset Information

MiR-337-3p improves metabolic-associated fatty liver disease through regulation of glycolipid metabolism.

ABSTRACT: Epigenetic regulations play crucial roles in the pathogenesis of metabolic-associated fatty liver disease; therefore, elucidating the biological functions of differential miRNAs helps us to understand the pathogenesis. Herein, we discovered miR-337-3p was decreased in patients with NAFLD from Gene Expression Omnibus dataset, which was replicated in various cell and mouse models with lipid disorders. Subsequently, overexpression of miR-337-3p in vivo could ameliorate hepatic lipid accumulation, reduce fasting blood glucose, and improve insulin resistance. Meanwhile, we determined miR-337-3p might influence multiple genes involved in glycolipid metabolism through mass spectrometry detection, bioinformatics analysis, and experimental verification. Finally, we selected HMGCR as a representative example to investigate the molecular mechanism of miR-337-3p regulating these genes, where the seed region of miR-337-3p bound to 3'UTR of HMGCR to inhibit HMGCR translation. In conclusion, we discovered a new function of miR-337-3p in glycolipid metabolism and that might be a new therapeutic target of MAFLD.

SUBMITTER: Xu X

PROVIDER: S-EPMC10665915 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature

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MiR-337-3p improves metabolic-associated fatty liver disease through regulation of glycolipid metabolism.

Xu Xiaoding X Yu Chuwei C He Hongxiu H Pan Xiangyu X Hou Aijun A Feng Jianxun J Tan Rongrong R Gong Likun L Chen Jing J Ren Jin J

iScience 20231028 11

Epigenetic regulations play crucial roles in the pathogenesis of metabolic-associated fatty liver disease; therefore, elucidating the biological functions of differential miRNAs helps us to understand the pathogenesis. Herein, we discovered miR-337-3p was decreased in patients with NAFLD from Gene Expression Omnibus dataset, which was replicated in various cell and mouse models with lipid disorders. Subsequently, overexpression of miR-337-3p <i>in vivo</i> could ameliorate hepatic lipid accumula ...[more]

PMID: 38026196

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Project description:Background and aimsRecently metabolic dysfunction-associated fatty liver disease (MAFLD) has been introduced and was defined as hepatic steatosis with either overweight, diabetes, and/or a combination of other metabolic risk factors. We investigated the application of the MAFLD criteria as compared with NAFLD.Approach and resultsWe performed a cross-sectional analysis within the Rotterdam Study, a large prospective population-based cohort. Participants who attended the liver ultrasound and transient elastography program between 2009 and 2014 were eligible for inclusion. Subsequently, individuals with viral hepatitis, alcohol intake >60 g/day, missing alcohol data, and/or missing body mass index were excluded. According to their NAFLD and MAFLD status based on metadata and ultrasound, participants were allocated in overlap fatty liver disease (FLD), NAFLD-only, MAFLD-only, or no FLD. Fibrosis was defined as liver stiffness ≥8.0 kPa. In our analysis, 5445 participants were included: 1866 (34.3%) had MAFLD and 1604 (29.5%) [Correction added on December 27, 2021 after first online publication: The preceding fragment was changed from "1623 (29.8%)"] had NAFLD. This resulted in 1547 (28.4%) [Correction added on December 27, 2021 after first online publication: The preceding fragment was changed from "1566 (28.8%)"] individuals with overlap FLD, 319 (5.9%) [Correction added on December 27, 2021 after first online publication: The preceding fragment was changed from "300 (5.5%)"] with MAFLD-only, 57 (1.0%) with NAFLD-only, and 3522 (64.7%) with no FLD. The MAFLD-only group was strongly associated with fibrosis (adjusted OR 5.30 [Correction added on December 27, 2021 after first online publication: The preceding fragment was changed from "OR 5.27"], p < 0.001) and log-transformed liver stiffness (adjusted beta 0.116, p < 0.001), as opposed to the NAFLD-only group, in which no cases of fibrosis were identified and no association with liver stiffness (adjusted beta 0.006, p = 0.90) was found.ConclusionsFLD is highly prevalent in the general population. However, not the NAFLD-only, but the MAFLD-only group was associated with fibrosis and higher liver stiffness-independent of demographic and lifestyle factors. We believe that using the MAFLD criteria will help improve the identification and treatment of patients with FLD at risk for fibrosis.

Dataset Information

MiR-337-3p improves metabolic-associated fatty liver disease through regulation of glycolipid metabolism.

Publications

MiR-337-3p improves metabolic-associated fatty liver disease through regulation of glycolipid metabolism.

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