Long noncoding RNA lnc_217 regulates hepatic lipid metabolism by modulating lipogenesis and fatty acid oxidation

• Published in: Journal of biomedical research Vol. 37; no. 6; pp. 448 - 459
• Main Authors: Yuan, Xiaoqing, Liu, Yawei, Yang, Xule, Huang, Yun, Shen, Xuan, Liang, Hui, Zhou, Hongwen, Wang, Qian, Zhang, Xu, Li, John Zhong
• Format: Journal Article
• Language: English
• Published: Editorial Department of Journal of Biomedical Research 01.11.2023
• Subjects: Original
• ISSN: 1674-8301; 2352-4685
• DOI: 10.7555/JBR.37.20230075

Nonalcoholic fatty liver disease (NAFLD) is considered a major health epidemic with an estimated 32.4% worldwide prevalence. No drugs have yet been approved and therapeutic nodes remain a major unmet need. Long noncoding RNAs are emerging as an important class of novel regulators influencing multiple biological processes and the pathogenesis of NAFLD. Herein, we described a novel long noncoding RNA, lnc_217, which was liver enriched and upregulated in high-fat diet-fed mice, and a genetic animal model of NAFLD. We found that liver specific knockdown of lnc_217 was resistant to high-fat diet-induced hepatic lipid accumulation and decreased serum lipid in mice. Mechanistically, we demonstrated that knockdown of lnc_217 not only decreased de novo lipogenesis by inhibiting sterol regulatory element binding protein-1c cleavage but also increased fatty acid β-oxidation through activation of peroxisome proliferator-activated receptor α and carnitine palmitoyltransferase-1α. Taken together, we conclude that lnc_217 may be a novel regulator of hepatic lipid metabolism and a potential therapeutic target for the treatment of hepatic steatosis and NAFLD-related metabolic disorders.