ABSTRACT
Obesity poses significant health risks and can negatively impact an individual’s quality of life. The human obesity phenotype results from the differentiation of pre-adipocytes into adipocytes, which leads to hypertrophy and hyperplasia in adipose tissue. The molecular mechanisms by which long non-coding RNAs (lncRNAs) modulate adipocyte differentiation, a process implicated in obesity development, remain poorly characterized. A lncRNA which suppressed the hepatic gluconeogenesis and lipogenesis (lncSHGL) was newly identified. Our research aims to elucidate the functional role and mechanistic underpinnings of suppressor of lncSHGL in adipocyte differentiation. We observed that lncSHGL expression progressively diminished during 3T3-L1 differentiation and was downregulated in the liver and perirenal adipose tissue of ob/ob mice. lncSHGL acts as a molecular sponge for miR-149, with Mospd3 identified as a target of miR-149.Overexpression of lncSHGL and inhibition of miR-149 led to suppressed 3T3-L1 proliferation, decreased lipid droplet accumulation, and attenuated promoter activity of PPARγ2 and C/EBPα. These changes consequently resulted in reduced expression of Cyclin D1, LPL, PPARγ2, AP2, and C/EBPα, as well as inhibited the PI3K/AKT/mTOR signaling pathway. In contrast, lncSHGL suppression yielded opposing outcomes. Moreover, the effects of lncSHGL overexpression and miR-149 inhibition on reduced expression of Cyclin D1, LPL, PPARγ2, AP2, and C/EBPα were reversible upon miR-149 overexpression and Mospd3 suppression. These findings were further validated in vivo. We also discovered a significant increase in methylation levels during 3T3-L1 differentiation, with lncSHGL highly expressed in the presence of a methylation inhibitor. In conclusion. lncSHGL methylation facilitates adipocyte differentiation by modulating the miR-149/Mospd3 axis. Targeting lncSHGL expression may represent a promising therapeutic strategy for obesity-associated adipogenesis, particularly in the context of fatty liver disease.
Disclosure statement
No potential conflict of interest was reported by the author(s).
Authors’ contributions
Conceptualization, X.H. and J.L.; methodology, X.H. and X.L.; software, X.H.; validation, X.H., X.L. and J.L.; formal analysis, M.M., M.P. and W.K.; investigation, X.H., X.L. and J.L; resources, X.H., X.L. and J.L.; data curation, X.H.; writing – original draft preparation, X.H; writing – review and editing, X.H., X.L and J.L; visualization, X.H.; supervision, J.L.; project administration, J.L.; funding acquisition, X.H. and J.L. All authors have read and agreed to the published version of the manuscript.
Availability of data and materials
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
Consent for publication
We have obtained consent to publish from the participants to report patient data.
Ethics approval and consent to participate
The study was reviewed and approved by the ethics committee of the first Affiliated Hospital of Xiamen University (Xiamen, China).