title: Fat mass- and obesity-associated gene Fto affects the dietary response in mouse white adipose tissue.
abstract: Common variants of human fat mass- and obesity-associated gene Fto have been linked with higher body mass index, but the biological explanation for the link has remained obscure. Recent findings suggest that these variants affect the homeobox protein IRX3. Here we report that FTO has a role in white adipose tissue which modifies its response to high-fat feeding. Wild type and Fto-deficient mice were exposed to standard or high-fat diet for 16 weeks after which metabolism, behavior and white adipose tissue morphology were analyzed together with adipokine levels and relative expression of genes regulating white adipose tissue adipogenesis and Irx3. Our results indicate that Fto deficiency increases the expression of genes related to adipogenesis preventing adipocytes from becoming hypertrophic after high-fat diet. In addition, we report a novel finding of increased Irx3 expression in Fto-deficient mice after high-fat feeding indicating a complex link between FTO, IRX3 and fat metabolism.
authors.affiliation: 1] Biocenter Oulu, University of Oulu, Oulu, Finland [2] Institute of Clinical Medicine, Department of Internal Medicine, University of Oulu, Oulu, Finland [3] Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland.
authors.forename: Justiina
authors.initials: J
authors.lastname: Ronkainen
authors.affiliation: 1] Biocenter Oulu, University of Oulu, Oulu, Finland [2] Institute of Clinical Medicine, Department of Internal Medicine, University of Oulu, Oulu, Finland [3] Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland.
authors.forename: Tuija J
authors.initials: TJ
authors.lastname: Huusko
authors.affiliation: 1] Biocenter Oulu, University of Oulu, Oulu, Finland [2] Faculty of Biochemistry and Molecular Medicine, Oulu Center for Cell-Matrix Research, University of Oulu, Oulu, Finland.
authors.forename: Raija
authors.initials: R
authors.lastname: Soininen
authors.affiliation: Department of Experimental and Clinical Medicine, Marche Polytechnic University, Ancona, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Mondini
authors.affiliation: Department of Experimental and Clinical Medicine, Marche Polytechnic University, Ancona, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Cinti
authors.affiliation: 1] Biocenter Oulu, University of Oulu, Oulu, Finland [2] Institute of Biomedicine, Department of Physiology, University of Oulu, Oulu, Finland.
authors.forename: Kari A
authors.initials: KA
authors.lastname: Mäkelä
authors.affiliation: 1] Biocenter Oulu, University of Oulu, Oulu, Finland [2] Institute of Biomedicine, Department of Physiology, University of Oulu, Oulu, Finland.
authors.forename: Miia
authors.initials: M
authors.lastname: Kovalainen
authors.affiliation: 1] Biocenter Oulu, University of Oulu, Oulu, Finland [2] Institute of Biomedicine, Department of Physiology, University of Oulu, Oulu, Finland.
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Herzig
authors.affiliation: 1] Biocenter Oulu, University of Oulu, Oulu, Finland [2] Department of Epidemiology and Biostatistics, MRC Health Protection Agency (HPA) Centre for Environment and Health, School of Public Health, Imperial College, London, United Kingdom [3] Center for Life Course Epidemiology, Faculty of Medicine, University of Oulu, Oulu, Finland [4] Unit of Primary Care, Oulu University Hospital, Oulu, Finland.
authors.forename: Marjo-Riitta
authors.initials: MR
authors.lastname: Järvelin
authors.affiliation: 1] Biocenter Oulu, University of Oulu, Oulu, Finland [2] Center for Life Course Epidemiology, Faculty of Medicine, University of Oulu, Oulu, Finland.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Sebert
authors.affiliation: 1] Biocenter Oulu, University of Oulu, Oulu, Finland [2] Institute of Clinical Medicine, Department of Internal Medicine, University of Oulu, Oulu, Finland [3] Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland.
authors.forename: Markku J
authors.initials: MJ
authors.lastname: Savolainen
authors.affiliation: 1] Biocenter Oulu, University of Oulu, Oulu, Finland [2] Institute of Clinical Medicine, Department of Internal Medicine, University of Oulu, Oulu, Finland [3] Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland.
authors.forename: Tuire
authors.initials: T
authors.lastname: Salonurmi
mesh_terms: D050156:Adipogenesis; D054392:Adipokines / Q000378:metabolism; D052242:Adiponectin / Q000096:biosynthesis; D052436:Adipose Tissue, White / Q000378:metabolism* / Q000473:pathology; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D000818:Animals; D059305:Diet, High-Fat; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D004734:Energy Metabolism; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D018398:Homeodomain Proteins / Q000378:metabolism; D020738:Leptin / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D006899:Mixed Function Oxygenases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism / Q000473:pathology; D007652:Oxo-Acid-Lyases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D054392:Adipokines; D052242:Adiponectin; D051275:Glucose Transporter Type 4; D018398:Homeodomain Proteins; C501599:Irx3 protein, mouse; D020738:Leptin; C495693:Slc2a4 protein, mouse; D014157:Transcription Factors; D006899:Mixed Function Oxygenases; C524916:FTO protein, mouse; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D007652:Oxo-Acid-Lyases