IGF2BP3 suppresses adipogenesis via m6A-dependent stabilization of FAM13A mRNA in 3T3-L1 adipocytes.
TL;DR
The unique role of the IGF2BP3-FAM13A axis in regulating adipocyte biology is revealed and its potential as a therapeutic target for obesity is suggested.
Abstract
Background
Dysregulated adipogenesis is a key pathogenic driver of obesity. This study aimed to delineate the role of family with sequence similarity 13, member A (FAM13A) in adipogenesis and to elucidate the molecular mechanisms underlying its abnormal expression.
Methods
C57BL/6J mice were subjected to a high-fat diet to establish an obesity model. 3T3-L1 cells were induced for adipogenic differentiation. Lipid accumulation was assessed by Oil Red O staining and enzymatic assay kits. Gene expression was analyzed using quantitative real-time polymerase chain reaction (qRT-PCR) and immunoblotting. The binding between insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) and FAM13A mRNA was verified by RNA electrophoretic mobility shift assays, RNA immunoprecipitation, and dual-luciferase reporter assays, while methylated RNA immunoprecipitation was employed to measure N6-methyladenosine (m6A) modification levels on FAM13A mRNA.
Results
FAM13A and IGF2BP3 were downregulated in adipose tissue of obese mice and during 3T3-L1 adipogenesis. Overexpression of FAM13A inhibited the adipogenic differentiation of 3T3-L1 cells. Furthermore, IGF2BP3 recognizes m6A-modified FAM13A, increasing its mRNA stability. Inhibition of FAM13A reversed the suppression of adipogenic differentiation caused by IGF2BP3 overexpression.
Conclusion
Our research revealed the unique role of the IGF2BP3-FAM13A axis in regulating adipocyte biology and suggested its potential as a therapeutic target for obesity.