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Table 1 The functions of RNA m6A methylation in metabolic diseases

From: RNA N6-methyladenosine: a promising molecular target in metabolic diseases

 m6A RegulatorsFunctionsRefs
T2DFTOPromoting the mRNA expression of FOXO1, G6PC, and DGAT2, which are associated with glucose and lipid metabolism[32]
METTL3Inhibiting 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]
METTL14Decreasing 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]
ObesityFTOPromoting 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]
WTAPSuppressing adipogenesis by promoting cell cycle transition in mitotic clonal expansion[89]
METTL3Suppressing adipogenesis by promoting cell cycle transition in mitotic clonal expansion[89]
Inhibiting adipogenesis via the depletion of ZFP217 and CCND1[92]
METTL14Suppressing adipogenesis by promoting cell cycle transition in mitotic clonal expansion[89]
YTHDF2Inhibiting 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]
NAFLDFTODown-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]
YTHDF2Increasing lipid accumulation by decreasing both PPARα mRNA lifetime and expression[105]
METTL3Increasing lipid accumulation by decreasing both PPARα mRNA lifetime and expression[105]
Hypertensionm6A-SNPsEncodIing β1-adrenoreceptor, a hypertension-susceptibility candidate gene[108, 109]
Altering BP-related gene expression, mRNA stability and homeostasis[110]
Cardiovascular diseasesFTODecreasing fibrosis and enhancing angiogenesis in mouse models of myocardial infarction[111]
METTL3Driving 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]
OsteoporosisMETTL3Inhibiting 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]
FTOPromoting 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 MDsALKBH5Expressing highly in organs enriched in immune cells with frequent immune reactions[10, 123]
METTL3Stimulating 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]
  1. m6A methylation plays crucial roles on the regulation of metabolic diseases, including obesity, type 2 diabetes, non-alcoholic fatty liver disease, hypertension, osteoporosis and immune-related metabolic diseases
  2. Refs references