title: The Demethylase Activity of FTO (Fat Mass and Obesity Associated Protein) Is Required for Preadipocyte Differentiation.
abstract: FTO (fat mass and obesity associated gene) was genetically identified to be associated with body mass index (BMI), presumably through functional regulation of energy homeostasis. However, the cellular and molecular mechanisms by which FTO functions remain largely unknown. Using 3T3-L1 preadipocyte as a model to study the role of FTO in adipogenesis, we demonstrated that FTO is functionally required for 3T3-L1 differentiation. FTO knock-down with siRNA inhibited preadipocyte differentiation, whereas ectopic over-expression of FTO enhanced the process. The demethylase activity of FTO is required for differentiation. Level of N6-methyladenosine (m6A) is decreased in cells over-expressing FTO. In contrast, overexpression of R96Q, a FTO missense mutant lack of demethylase activity, had no effect on cellular m6A level and impeded differentiation. Treatment with Rosiglitazone, a PPARγ agonist, could overcome the differentiation inhibition imposed by R96Q mutant, suggesting the effect of FTO is mediated through PPARγ.
authors.affiliation: Space Biology Research and Technology Center, China Academy of Space Technology, Beijing Engineering Research Center of Space Biology, Beijing, 100190, China.
authors.forename: Meizi
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Space Biology Research and Technology Center, China Academy of Space Technology, Beijing Engineering Research Center of Space Biology, Beijing, 100190, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Space Biology Research and Technology Center, China Academy of Space Technology, Beijing Engineering Research Center of Space Biology, Beijing, 100190, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Ma
authors.affiliation: Space Biology Research and Technology Center, China Academy of Space Technology, Beijing Engineering Research Center of Space Biology, Beijing, 100190, China.
authors.forename: Feima
authors.initials: F
authors.lastname: Guo
authors.affiliation: Space Biology Research and Technology Center, China Academy of Space Technology, Beijing Engineering Research Center of Space Biology, Beijing, 100190, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Cao
authors.affiliation: Space Biology Research and Technology Center, China Academy of Space Technology, Beijing Engineering Research Center of Space Biology, Beijing, 100190, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: School of Life Sciences, Tsinghua University, Beijing, 100084, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhou
authors.affiliation: School of Life Sciences, Tsinghua University, Beijing, 100084, China.
authors.forename: Jijie
authors.initials: J
authors.lastname: Chai
authors.affiliation: Space Biology Research and Technology Center, China Academy of Space Technology, Beijing Engineering Research Center of Space Biology, Beijing, 100190, China.
authors.forename: Wenqing
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Space Biology Research and Technology Center, China Academy of Space Technology, Beijing Engineering Research Center of Space Biology, Beijing, 100190, China.
authors.forename: Renbin
authors.initials: R
authors.lastname: Zhao
mesh_terms: D041721:3T3-L1 Cells; D000241:Adenosine / Q000031:analogs & derivatives / Q000378:metabolism; D017667:Adipocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D050156:Adipogenesis / Q000187:drug effects / Q000502:physiology*; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000378:metabolism*; D020869:Gene Expression Profiling; D007004:Hypoglycemic Agents / Q000494:pharmacology; D051379:Mice; D009765:Obesity; D047495:PPAR gamma / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D011506:Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology
chemical_list: D015415:Biomarkers; D007004:Hypoglycemic Agents; D047495:PPAR gamma; D011506:Proteins; D034741:RNA, Small Interfering; D045162:Thiazolidinediones; D000077154:Rosiglitazone; C010223:N-methyladenosine; C524916:FTO protein, mouse; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D015254:DNA Modification Methylases; D000241:Adenosine