Table 1 The functions of RNA m⁶A methylation in metabolic diseases

T2D

FTO

Promoting the mRNA expression of FOXO1, G6PC, and DGAT2, which are associated with glucose and lipid metabolism

[32]

METTL3

Inhibiting hepatic insulin sensitivity via N6-methylation of FASN mRNA and promoting fatty acid metabolism

[69]

Upregulating insulin/IGF1–AKT–PDX1 pathway in human β-cells

[71]

METTL14

Decreasing cell death and the changes of cell differentiation of β-cells, increasing β-cell mass and insulin secretion

[70]

Upregulating insulin/IGF1–AKT–PDX1 pathway in human β-cells

[71]

Obesity

FTO

Promoting adipogenesis by inhibiting the Wnt/β-catenin signaling pathway

[86]

Promoting autophagy and adipogenesis via increasing the expression of ATG5 and ATG7

[87]

Promoting adipocyte proliferation via enhancing the expression of the pro-adipogenic short isoform of RUNX1

[77]

WTAP

Suppressing adipogenesis by promoting cell cycle transition in mitotic clonal expansion

[89]

METTL3

Suppressing adipogenesis by promoting cell cycle transition in mitotic clonal expansion

[89]

Inhibiting adipogenesis via the depletion of ZFP217 and CCND1

[92]

METTL14

Suppressing adipogenesis by promoting cell cycle transition in mitotic clonal expansion

[89]

YTHDF2

Inhibiting autophagy and adipogenesis by decreasing protein expression of ATG5 and ATG7 and shortening the lifespan of their m⁶A-modified mRNAs

[87]

Suppressing adipogenesis by increasing m⁶A methylation of CCNA2 and CDK2 and reversing the methylation effect of FTO on CCNA2 and CDK2

[90, 91]

Inhibiting adipogenesis via the downregulation of CCND1

[92]

NAFLD

FTO

Down-regulating mitochondrial content and up-regulating TG deposition

[101]

Promoting hepatic fat accumulation by increasing the expression of lipogenic genes, including FASN, SCD and MOGAT1, and intracellular TG level in HepG2 cells

[101]

Increasing oxidative stress and lipid deposition

[99]

YTHDF2

Increasing lipid accumulation by decreasing both PPARα mRNA lifetime and expression

[105]

METTL3

Increasing lipid accumulation by decreasing both PPARα mRNA lifetime and expression

[105]

Hypertension

m⁶A-SNPs

EncodIing β1-adrenoreceptor, a hypertension-susceptibility candidate gene

[108, 109]

Altering BP-related gene expression, mRNA stability and homeostasis

[110]

Cardiovascular diseases

FTO

Decreasing fibrosis and enhancing angiogenesis in mouse models of myocardial infarction

[111]

METTL3

Driving cardiomyocyte hypertrophy by catalyzing methylation of m⁶A on certain subsets of mRNAs

[112]

Decreasing eccentric cardiomyocyte remodeling and dysfunction

[112]

Inhibiting cellular autophagic flux and promoting apoptosis in hypoxia/reoxygenation-treated cardiomyocytes

[113]

Osteoporosis

METTL3

Inhibiting adipogenesis and adipogenic differentiation via JAK1/STAT5/C/EBPβ pathway in bone marrow stem cells

[119]

Inhibiting osteoporosis pathological phenotypes, consisting of decreased bone mass and increased marrow adiposity via PTH/PTH1R signaling axis

[118]

FTO

Promoting the differentiation of adipocyte and osteoblast by upregulating GDF11–FTO–PPARγ signalling way

[116]

Enhancing the stability of mRNA of proteins which function to protect osteoblasts from genotoxic damage through Hspa1a–NF-κB signaling way

[120]

Immune-related MDs

ALKBH5

Expressing highly in organs enriched in immune cells with frequent immune reactions

[10, 123]

METTL3

Stimulating T cell activation and the development of T lymphocytes in the thymus by regulating the translation of CD40, CD80 and TLR4 signaling adaptor TIRAP transcripts in dendritic cells

[124, 125]

Maintaining T cell homeostasis and differentiation by targeting the IL-7/STAT5/SOCS pathways

[126]