{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Xiao L"],"funding":["NIDDK NIH HHS","NHGRI NIH HHS","American Diabetes Association","National Institutes of Health"],"pagination":["2207-2227.e9"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11891809"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["36(10)"],"pubmed_abstract":["Brown adipose tissue (BAT) regulates systemic metabolism by releasing signaling lipids. N<sup>6</sup>-methyladenosine (m<sup>6</sup>A) is the most prevalent and abundant post-transcriptional mRNA modification and has been reported to regulate BAT adipogenesis and energy expenditure. Here, we demonstrate that the absence of m<sup>6</sup>A methyltransferase-like 14 (METTL14) modifies the BAT secretome to improve systemic insulin sensitivity independent of UCP1. Using lipidomics, we identify prostaglandin E2 (PGE2) and prostaglandin F2a (PGF2a) as BAT-secreted insulin sensitizers. PGE2 and PGF2a inversely correlate with insulin sensitivity in humans and protect mice from high-fat-diet-induced insulin resistance by suppressing specific AKT phosphatases. Mechanistically, METTL14-mediated m<sup>"],"journal":["Cell metabolism"],"pubmed_title":["m&lt;sup&gt;6&lt;/sup&gt;A mRNA methylation in brown fat regulates systemic insulin sensitivity via an inter-organ prostaglandin signaling axis independent of UCP1."],"pmcid":["PMC11891809"],"funding_grant_id":["K99 DK135927","RC2 DK139552","UC4 DK116278","R01 DK067536","P30 DK036836","RM1 HG008935"],"pubmed_authors":["Ju CW","Tsuji T","He C","Mannisto V","Wei JB","Bluher M","DiStefano-Forti A","Cypess AM","Manninen SM","Xiao L","Pihlajamaki J","Hu J","Tseng YH","Wei S","Kulkarni RN","Cero C","Ijaduola O","De Jesus DF"],"additional_accession":[]},"is_claimable":false,"name":"m&lt;sup&gt;6&lt;/sup&gt;A mRNA methylation in brown fat regulates systemic insulin sensitivity via an inter-organ prostaglandin signaling axis independent of UCP1.","description":"Brown adipose tissue (BAT) regulates systemic metabolism by releasing signaling lipids. N<sup>6</sup>-methyladenosine (m<sup>6</sup>A) is the most prevalent and abundant post-transcriptional mRNA modification and has been reported to regulate BAT adipogenesis and energy expenditure. Here, we demonstrate that the absence of m<sup>6</sup>A methyltransferase-like 14 (METTL14) modifies the BAT secretome to improve systemic insulin sensitivity independent of UCP1. Using lipidomics, we identify prostaglandin E2 (PGE2) and prostaglandin F2a (PGF2a) as BAT-secreted insulin sensitizers. PGE2 and PGF2a inversely correlate with insulin sensitivity in humans and protect mice from high-fat-diet-induced insulin resistance by suppressing specific AKT phosphatases. Mechanistically, METTL14-mediated m<sup>","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Oct","modification":"2026-06-04T00:16:43.713Z","creation":"2026-05-03T03:12:00.385Z"},"accession":"S-EPMC11891809","cross_references":{"pubmed":["39255799"],"doi":["10.1016/j.cmet.2024.08.006"]}}