Fto-Deficiency Affects the Gene and MicroRNA Expression Involved in Brown Adipogenesis and Browning of White Adipose Tissue in Mice.
Genetic variants in the fat mass- and obesity-associated geneFtoare linked to the onset of obesity in humans. The causal role of the FTO protein in obesity is supported by evidence obtained from transgenic mice; however, the underlying molecular pathways pertaining to the role of FTO in obesity have yet to be established. In this study, we investigate theFtogene in mouse brown adipose tissue and in the browning process of white adipose tissue. We analyze distinct structural and molecular factors in brown and white fat depots ofFto-deficient mice under normal and obesogenic conditions. We report significant alterations in the morphology of adipose tissue depots and the expression of mRNA and microRNA related to brown adipogenesis and metabolism inFto-deficient mice. Furthermore, we show that high-fat feeding does not attenuate the browning process ofFto-deficient white adipose tissue as observed in wild-type tissue, suggesting a triggering effect of the FTO pathways by the dietary environment.
Biocenter Oulu, University of Oulu, FI-90220 Oulu, Finland. justiina.ronkainen@oulu.fi.|Faculty of Medicine, Department of Internal Medicine, University of Oulu, FI-90220 Oulu, Finland. justiina.ronkainen@oulu.fi.|Medical Research Center Oulu, Oulu University Hospital and University of Oulu, FI-90220 Oulu, Finland. justiina.ronkainen@oulu.fi.
Justiina
J
Ronkainen
Department of Experimental and Clinical Medicine, Marche Polytechnic University, IT-60126 Ancona, Italy. ele_mondini@yahoo.it.
Eleonora
E
Mondini
Department of Experimental and Clinical Medicine, Marche Polytechnic University, IT-60126 Ancona, Italy. cinti_francesca@hotmail.com.
Francesca
F
Cinti
Department of Experimental and Clinical Medicine, Marche Polytechnic University, IT-60126 Ancona, Italy. cinti@univpm.it.
Saverio
S
Cinti
Biocenter Oulu, University of Oulu, FI-90220 Oulu, Finland. sylvain.sebert@oulu.fi.|Center for Life-Course Health Research, University of Oulu, FI-90220 Oulu, Finland. sylvain.sebert@oulu.fi.
Sylvain
S
Sebért
Biocenter Oulu, University of Oulu, FI-90220 Oulu, Finland. markku.savolainen@oulu.fi.|Faculty of Medicine, Department of Internal Medicine, University of Oulu, FI-90220 Oulu, Finland. markku.savolainen@oulu.fi.|Medical Research Center Oulu, Oulu University Hospital and University of Oulu, FI-90220 Oulu, Finland. markku.savolainen@oulu.fi.
Markku J
MJ
Savolainen
Biocenter Oulu, University of Oulu, FI-90220 Oulu, Finland. tuire.salonurmi@oulu.fi.|Faculty of Medicine, Department of Internal Medicine, University of Oulu, FI-90220 Oulu, Finland. tuire.salonurmi@oulu.fi.|Medical Research Center Oulu, Oulu University Hospital and University of Oulu, FI-90220 Oulu, Finland. tuire.salonurmi@oulu.fi.
Tuire
T
Salonurmi
D050156:Adipogenesis / Q000235:genetics*; D002001:Adipose Tissue, Brown / Q000378:metabolism* / Q000473:pathology; D052436:Adipose Tissue, White / Q000378:metabolism* / Q000473:pathology; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO / Q000172:deficiency / Q000235:genetics*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D059305:Diet, High-Fat; D004734:Energy Metabolism / Q000235:genetics; D005786:Gene Expression Regulation; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009765:Obesity / Q000209:etiology / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D022702:Receptors, Adrenergic, beta-3 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D000071256:Uncoupling Protein 1 / Q000235:genetics / Q000378:metabolism
D015415:Biomarkers; D022782:CCAAT-Enhancer-Binding Protein-beta; C545013:Cebpb protein, mouse; D004268:DNA-Binding Proteins; C582652:MIRN130 microRNA, mouse; C546119:MIRN378 microRNA, mouse; D035683:MicroRNAs; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; C521133:Prdm16 protein, mouse; D012333:RNA, Messenger; D022702:Receptors, Adrenergic, beta-3; D014157:Transcription Factors; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1; C524916:FTO protein, mouse; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO
FTO; brown adipose tissue (BAT); gene expression; high-fat diet; microRNA expression; white adipose tissue (WAT) browning