N 6 -methyladenine (m 6 A) is the most prevalent type of internal RNA methylation in eukaryotic mRNA and plays critical roles in regulating gene expression for fundamental cellular processes and diverse physiological functions. Recent evidence indicates that m 6 A methylation regulates physiology and metabolism, and m 6 A has been increasingly implicated in a variety of human diseases, including obesity, diabetes, metabolic syndrome and cancer. Conversely, nutrition and diet can modulate or reverse m 6 A methylation patterns on gene expression. In this review, we summarize the recent progress in the study of the m 6 A methylation mechanisms and highlight the crosstalk between m 6 A modification, nutritional physiology and metabolism. KEYWORDS epitranscriptomic, M 6 A RNA methylation, metabolism, nutrition 1 | INTRODUCTION More than 100 types of chemical modifications have been discovered in cellular RNAs. 1 Reversible RNA modifications are an emerging layer of posttranscriptional gene regulation, 2,3 which exerts a large number of physiological processes and biological functions. 4,5 As a novel epitranscriptomic marker, the dynamic and reversible chemical N 6methyladenine (m 6 A) modification is the most abundant internal modification in mRNA. In mammals, plants and some prokaryotes, m 6 A is widely involved in mRNA metabolism, including mRNA stability, 6 mRNA splicing, 7,8 RNA nucleation, 9 RNA-protein interactions 10 and mRNA translation. 11The m 6 A modification plays an important role in nutritional physiology and metabolism, such as controlling circadian rhythms, 12,13 lipid accumulation 14 and adipogenesis. 15,16 The dysregulation of m 6 A patterns causes abnormal gene expression and functions, aberrant cell differentiation and cellular homeostasis imbalance, leading to the occurrence of certain inflammatory states, metabolic diseases and cancer. 9,17,18 Therefore, the effects of m 6 A RNA methylation on physiology and metabolism have become a research hotspot in the RNA Abbreviations: m 6 A, N 6 -methyladenine; 3'-UTRs, 3'untranslated regions; CDS, coding sequence; MTC, methyltransferase cpmplex; METTL3, methyltransferase-like 3; METTL14, methyltransferase-like 14; WTAP, Wilms' tumour 1-associating protein; ZC3H13, zinc finger CCCH-type containing 13; RBM15/15B, RNA binding motif protein 15/15B; FTO, fat mass and obesity-associated protein; ALKBH5, AlkB homolog 5; YTHDF1/2/3, YTH domain family 1/2/3; YTHDC1/2, YTH domain containing 1/2; SAM, S-adenosylmethionine; hm 6 A, N 6hydroxymethyladenosine; f 6 A, N 6 -formyladenosine; A, adenosine; m 6 A m , N 6 ,2'-O-dimethyladenosine; DCP2, decapping mRNA 2; snRNA, small nuclear RNA; eIF3, eukaryotic initiation factor 3; SRSF3, serine/arginine-rich splicing factor 3; SRSF10, serine/arginine-rich splicing factor 10; HNRNPA2B1, heterogenous nuclear ribonucleoprotein A2B1; HNRNPC, heterogenous nuclear ribonucleoprotein C; DGCR8, DiGeorge syndrome critical region gene 8; IGF2BP1/2/3, insulin-like growth factor 2 mRNA-binding protein 1/2/3; T2DM, type 2 diabetes melli...