Fto-Deficiency Affects the Gene and MicroRNA Expression Involved in Brown Adipogenesis and Browning of White Adipose Tissue in Mice

Justiina Ronkainen; Eleonora Mondini; Francesca Cinti; Saverio Cinti; Sylvain Sebért; Markku J Savolainen; Tuire Salonurmi

doi:10.3390/ijms17111851

Fto-Deficiency Affects the Gene and MicroRNA Expression Involved in Brown Adipogenesis and Browning of White Adipose Tissue in Mice

Int J Mol Sci. 2016 Nov 7;17(11):1851. doi: 10.3390/ijms17111851.

Authors

Justiina Ronkainen^{1

2

3}, Eleonora Mondini⁴, Francesca Cinti⁵, Saverio Cinti⁶, Sylvain Sebért^{7

8}, Markku J Savolainen^{9

10

11}, Tuire Salonurmi^{12

13

14}

Affiliations

¹ Biocenter Oulu, University of Oulu, FI-90220 Oulu, Finland. [email protected].
² Faculty of Medicine, Department of Internal Medicine, University of Oulu, FI-90220 Oulu, Finland. [email protected].
³ Medical Research Center Oulu, Oulu University Hospital and University of Oulu, FI-90220 Oulu, Finland. [email protected].
⁴ Department of Experimental and Clinical Medicine, Marche Polytechnic University, IT-60126 Ancona, Italy. [email protected].
⁵ Department of Experimental and Clinical Medicine, Marche Polytechnic University, IT-60126 Ancona, Italy. [email protected].
⁶ Department of Experimental and Clinical Medicine, Marche Polytechnic University, IT-60126 Ancona, Italy. [email protected].
⁷ Biocenter Oulu, University of Oulu, FI-90220 Oulu, Finland. [email protected].
⁸ Center for Life-Course Health Research, University of Oulu, FI-90220 Oulu, Finland. [email protected].
⁹ Biocenter Oulu, University of Oulu, FI-90220 Oulu, Finland. [email protected].
¹⁰ Faculty of Medicine, Department of Internal Medicine, University of Oulu, FI-90220 Oulu, Finland. [email protected].
¹¹ Medical Research Center Oulu, Oulu University Hospital and University of Oulu, FI-90220 Oulu, Finland. [email protected].
¹² Biocenter Oulu, University of Oulu, FI-90220 Oulu, Finland. [email protected].
¹³ Faculty of Medicine, Department of Internal Medicine, University of Oulu, FI-90220 Oulu, Finland. [email protected].
¹⁴ Medical Research Center Oulu, Oulu University Hospital and University of Oulu, FI-90220 Oulu, Finland. [email protected].

Abstract

Genetic variants in the fat mass- and obesity-associated gene Fto are 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 the Fto gene 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 of Fto-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 in Fto-deficient mice. Furthermore, we show that high-fat feeding does not attenuate the browning process of Fto-deficient white adipose tissue as observed in wild-type tissue, suggesting a triggering effect of the FTO pathways by the dietary environment.

Keywords: FTO; brown adipose tissue (BAT); gene expression; high-fat diet; microRNA expression; white adipose tissue (WAT) browning.

MeSH terms

Adipogenesis / genetics*
Adipose Tissue, Brown / metabolism*
Adipose Tissue, Brown / pathology
Adipose Tissue, White / metabolism*
Adipose Tissue, White / pathology
Alpha-Ketoglutarate-Dependent Dioxygenase FTO / deficiency
Alpha-Ketoglutarate-Dependent Dioxygenase FTO / genetics*
Animals
Biomarkers / metabolism
CCAAT-Enhancer-Binding Protein-beta / genetics
CCAAT-Enhancer-Binding Protein-beta / metabolism
DNA-Binding Proteins / genetics
DNA-Binding Proteins / metabolism
Diet, High-Fat
Energy Metabolism / genetics
Gene Expression Regulation
Male
Mice
Mice, Knockout
MicroRNAs / genetics*
MicroRNAs / metabolism
Obesity / etiology
Obesity / genetics*
Obesity / metabolism
Obesity / pathology
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / genetics
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / metabolism
RNA, Messenger / genetics
RNA, Messenger / metabolism
Receptors, Adrenergic, beta-3 / genetics
Receptors, Adrenergic, beta-3 / metabolism
Signal Transduction
Transcription Factors / genetics
Transcription Factors / metabolism
Uncoupling Protein 1 / genetics
Uncoupling Protein 1 / metabolism

Substances

Biomarkers
CCAAT-Enhancer-Binding Protein-beta
Cebpb protein, mouse
DNA-Binding Proteins
MIRN130 microRNA, mouse
MIRN378 microRNA, mouse
MicroRNAs
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
Ppargc1a protein, mouse
Prdm16 protein, mouse
RNA, Messenger
Receptors, Adrenergic, beta-3
Transcription Factors
Ucp1 protein, mouse
Uncoupling Protein 1
FTO protein, mouse
Alpha-Ketoglutarate-Dependent Dioxygenase FTO