miR-32-5p induces hepatic steatosis and hyperlipidemia by triggering de novo lipogenesis.

Autor: Wang YD; The First Affiliated Hospital, Department of Metabolism and Endocrinology, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China., Wu LL; The First Affiliated Hospital, Department of Gastrointestinal Surgery, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China., Mai YN; The First Affiliated Hospital, Department of Metabolism and Endocrinology, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China., Wang K; The First Affiliated Hospital, Department of Metabolism and Endocrinology, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China., Tang Y; The First Affiliated Hospital, Department of Metabolism and Endocrinology, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China., Wang QY; The First Affiliated Hospital, Department of Metabolism and Endocrinology, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China., Li JY; The First Affiliated Hospital, Department of Metabolism and Endocrinology, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China., Jiang LY; The First Affiliated Hospital, Department of Metabolism and Endocrinology, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China., Liao ZZ; The First Affiliated Hospital, Department of Metabolism and Endocrinology, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China., Hu C; The First Affiliated Hospital, Department of Metabolism and Endocrinology, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China., Wang YY; The First Affiliated Hospital, Department of Metabolism and Endocrinology, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China., Liu JJ; The First Affiliated Hospital, Department of Metabolism and Endocrinology, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China., Liu JH; The First Affiliated Hospital, Department of Metabolism and Endocrinology, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China. Electronic address: jianghua990@126.com., Xiao XH; The First Affiliated Hospital, Department of Metabolism and Endocrinology, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China. Electronic address: xinhua0102@163.com.
Jazyk: angličtina
Zdroj: Metabolism: clinical and experimental [Metabolism] 2023 Sep; Vol. 146, pp. 155660. Date of Electronic Publication: 2023 Jul 13.
DOI: 10.1016/j.metabol.2023.155660
Abstrakt: Background and Objectives: MicroRNA-dependent regulation of hepatic lipid metabolism has been recognized recently as a key pathological mechanism contributing to the development of NAFLD. However, whether miR-32-5p (miR-32) plays a role in lipid metabolism or contributes to NAFLD remains unclear.
Methods and Results: A marked increase in miR-32 expression was observed in liver samples from patients and mice with NAFLD, as well as in palmitate-induced hepatocytes. Hepatocyte-specific miR-32 knockout (miR-32-HKO) dramatically ameliorated hepatic steatosis and metabolic disorders in high-fat diet-fed mice. Conversely, hepatic miR-32 overexpression markedly exacerbated the progression of these abnormalities. Further, combinational analysis of transcriptomics and lipidomics suggested that miR-32 was a key trigger for de novo lipogenesis in the liver. Mechanistically, RNA sequencing, luciferase assay and adenovirus-mediated downstream gene rescue assay demonstrated that miR-32 directly bound to insulin-induced gene 1 (INSIG1) and subsequently activated sterol regulatory element binding protein-mediated lipogenic gene programs, thereby promoting hepatic lipid accumulation and metabolic disorders. Notably, pharmacological administration of miR-32 antagonist significantly inhibited palmitate-induced triglyceride deposition in hepatocytes and markedly mitigated hepatic steatosis and metabolic abnormalities in obesity-associated NAFLD mice.
Conclusion: miR-32 is an important checkpoint for lipogenesis in the liver, and targeting miR-32 could be a promising therapeutic approach for NAFLD treatment.
Competing Interests: Declaration of competing interest The authors declare no conflicts of interests.
(Copyright © 2023. Published by Elsevier Inc.)
Databáze: MEDLINE
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