biostudies-literatureUnknown12(1)Ben-Haim MSHerczeg Institute of AgingFlight Attendant Medical Research InstituteEsther B. Kahn Charitable FoundationThe Ernest and Bonnie Beutler Research Program.The prevalent m⁶Am mRNA cap modification was recently identified as a valid target for removal by the human obesity gene FTO along with the previously established m⁶A mRNA modification. However, the deposition and dynamics of m⁶Am in regulating obesity are unknown. Here, we investigate the liver m⁶A/m methylomes in mice fed on a high fat Western-diet and in ob/ob mice. We find that FTO levels are elevated in fat mice, and that genes which lost m⁶Am marking under obesity are overly downregulated, including the two fatty-acid-binding proteins FABP2, and FABP5. Furthermore, the cellular perturbation of FTO correspondingly affect protein levels of its targets. Notably, generally m⁶Am- but not m⁶A-methylated genes, areNature communications7185https://www.ebi.ac.uk/biostudies/studies/S-EPMC8664860biostudies-literatureDynamic regulation of N⁶,2'-O-dimethyladenosine (m⁶Am) in obesity.PMC8664860Cohen HYKol NRechavi GHershkovitz VMoshitch-Moshkovitz SPinto YAmariglio NBen-Haim MSDiamant-Levi TBeeri MSfalseDynamic regulation of N⁶,2'-O-dimethyladenosine (m⁶Am) in obesity.The prevalent m⁶Am mRNA cap modification was recently identified as a valid target for removal by the human obesity gene FTO along with the previously established m⁶A mRNA modification. However, the deposition and dynamics of m⁶Am in regulating obesity are unknown. Here, we investigate the liver m⁶A/m methylomes in mice fed on a high fat Western-diet and in ob/ob mice. We find that FTO levels are elevated in fat mice, and that genes which lost m⁶Am marking under obesity are overly downregulated, including the two fatty-acid-binding proteins FABP2, and FABP5. Furthermore, the cellular perturbation of FTO correspondingly affect protein levels of its targets. Notably, generally m⁶Am- but not m⁶A-methylated genes, are2021-01-01T00:00:00Z2021 Dec2026-05-09T15:13:13.119Z2024-11-07T13:37:25.609ZS-EPMC86648603489362010.1038/s41467-021-27421-2