Table 1.
The role of N6‐methyladenosine modification in adipogenesis
| Upstream regulators | m6A regulators | Target genes | Function and mechanism | Reference |
|---|---|---|---|---|
| – | FTO | RUNX1T1 | FTO controls the exonic splicing of RUNX1T1 via demethylation‐dependent manner and promotes the expression of RUNX1T1‐S isoform and adipogenesis of mouse 3T3‐L1 preadipocytes. | 7 |
| – | FTO | RUNX1T1 | FTO enhances the expression of the RUNX1T1‐S isoform of RUNX1T1 and mitotic clonal expansion via demethylation‐dependent manner, thus promoting adipogenesis in mice. | 56 |
| – | FTO | PPARG | FTO promotes mouse 3T3‐L1 preadipocytes differentiation by decreasing m6A level. Mechanistically, FTO exerts its effect upstream of PPARG during adipogenesis. | 57 |
| GDF11 | FTO | PPARG | FTO demethylates the mRNA of PPARG, leading to the increase in the expression of PPARG mRNA, thus favoring the mouse BMSCs to differentiate to adipocytes in human and mice. GDF11 significantly upregulated the expression of FTO | 61 |
| – | FTO/YTHDF2 | CCNA2, CDK2 | FTO reduces the m6A levels of CCNA2 and CDK2, promotes the protein expression of CCNA2 and CDK2 in YTHDF2‐dependent manner, thus reducing cell cycle progress and inducing adipogenesis of mouse 3T3‐L1 preadipocytes | 58 |
| – | FTO/YTHDF2 | ATG5, ATG7 | FTO reduces the m6A levels of ATG5 and ATG7, resulting in upregulated expression levels of ATG5 and ATG7 in a YTHDF2‐dependent manner, promoting autophagosome formation, autophagy and adipogenesis in mice | 59 |
| – | FTO/YTHDF2 | JAK2 | FTO reduces the m6A level of JAK2, and inhibits mRNA degradation in a YTHDF2‐dependent manner, thus promoting adipogenesis in porcine and mouse preadipocytes | 61 |
| EGCG | FTO | – | EGCG inhibits expression of FTO, and increases m6A levels of CCNA2 and CDK2 mRNA, resulting in decreased protein levels of CCNA2 and CDK2 in YTHDF2‐dependent manner, therefore inhibiting adipogenic differentiation of 3T3L1 cells by blocking the mitotic clonal expansion at the early stage of adipocyte differentiation. | 62 |
| ZFP217 | FTO/YTHDF2 | – | Zfp217 induces the increase of FTO, and promotes the adipogenic differentiation of 3T3L1 cells. Furthermore, the interaction of Zfp217 with YTHDF2 is critical for allowing FTO to maintain its interaction with m6A sites on various mRNAs | 63 |
| miR‐149‐3p | FTO | – | miR‐149‐3p mimic decreased the adipogenic differentiation potential of mouse BMSCs by binding to the 3′UTR of the FTO mRNA, inducing the decreased expression of FTO | 64 |
| NADP | FTO | – | NADP directly binds FTO, increases FTO activity, and promotes RNA m6A demethylation and adipogenesis in mice. | 65 |
| – | METTL3/FTO | – | METTL3 positively correlated with m6A levels and inhibited adipogenesis, FTO negatively regulated m6A levels and promoted adipogenesis in porcine adipocytes | 51 |
| – | METTL3/METTL14/WTAP | CCNA2 | WTAP‐METTL3‐METTL14 complex promotes the expression of CCNA2 and cell cycle transition in mitotic clonal expansion, thus inducing adipogenesis in mice. | 66 |
| – | METTL3/YTHDF2 | JAK1 | METTL3 increases mRNA m6A levels of JAK1, leading to reduced expression of JAK1 via a YTHDF2‐dependent manner, then inhibits the activation of JAK1/STAT5/C/EBPβ pathway and adipogenesis in porcine BMSCs. | 67 |
| ZFP217 | METTL3/YTHDF2 | CCND1 | ZFP217 decreases the expression of METTL3, subsequently decreasing the m6A level of CCND1 mRNA and increasing protein expression of CCND1 in YTHDF2‐dependent manner, thus inducing cell‐cycle progression and promoting adipogenesis in mouse 3T3‐L1 preadipocytes. | 68 |
| – | FTO/YTHDF1 | MTCH2 | m6A enhances MTCH2 translation via a YTHDF1‐dependent pathway and promotes adipogenesis in pigs. | 69 |
| – | YTHDF2 | FAM134B | Loss of m6A on FAM134B mRNA blocks its decay and promotes its translation via a YTHDF2‐dependent pathway, thus promoting porcine preadipocytes adipogenic differentiation | 70 |
BMSCs, bone marrow stem cells; CCNA2, cyclin A2; CCND1, cyclin D1; CDK2, cyclin‐dependent kinase 2; EGCG, epigallocatechin gallate; FTO, fat mass and obesity‐associated protein; GDF11, growth differentiation factor 11; JAK1, Janus kinase 1; JAKC2, Janus kinase 2; m6A, N6‐methyladenosine; METTL3, methyltransferase‐like protein 3; MTCH2, mitochondrial carrier 2; mRNA, messenger ribonucleic acid; NADP, nicotinamide adenine dinucleotide phosphate; STAT5, activator of transcription 5; ZFP217, zinc finger protein 217.