Gene expression of FTO in human subcutaneous adipose tissue, peripheral blood mononuclear cells and adipocyte cell line.
OBJECTIVE
The common polymorphism rs9939609 of the fat mass and obesity-associated gene (FTO) is strongly associated with obesity, but the biological function is still unknown. We compared the FTO gene expression in subcutaneous adipose tissue and peripheral blood mononuclear cells (PBMCs) between overweight and normal weight individuals. We also investigated if mRNA levels of FTO in adipose tissue correlated with the adiposity or inflammatory markers and mRNA levels of genes involved in the response to hypoxia (HIF-1a) and cell death(HMGB1).


RESULTS
The mRNA expression of FTO in adipose tissue was greater in obese than normal weight individuals (p < 0.001), but there was no difference in FTO expression in PBMCs. FTO mRNA levels did not correlate with adiposity or inflammatory markers and FTO expression was not influenced by the FTO rs9939609 genotype. FTO mRNA level correlated positively with gene expression levels of HIF-1a and HMGB1 in subcutaneous adipose tissue (r = 0.59, p < 0.001; r = 0.69, p < 0.001, respectively; adjusted for BMI and adipocyte cell size).


CONCLUSIONS
Altogether, FTO expression appeared not to have a well-defined impact on clinical or biochemical parameters comprising the metabolic syndrome. The correlations with the genes related to hypoxia and cell death suggest novel biological activities for FTO.
Institute of Public Health and Clinical Nutrition, Department of Clinical Nutrition, Food and Health Research Centre, University of Eastern Finland, Kuopio, Finland. tiina.lappalainen@uef.fi
Tiina
T
Lappalainen
Marjukka
M
Kolehmainen
Ursula
U
Schwab
Leena
L
Pulkkinen
Vanessa D F
VD
de Mello
Maija
M
Vaittinen
David E
DE
Laaksonen
Kaisa
K
Poutanen
Matti
M
Uusitupa
Helena
H
Gylling
D017667:Adipocytes / Q000502:physiology*; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D002097:C-Reactive Protein / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D005838:Genotype; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000235:genetics / Q000378:metabolism; D016133:Polymerase Chain Reaction / Q000379:methods; D011110:Polymorphism, Genetic; D011506:Proteins / Q000235:genetics*; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D012016:Reference Values; D050151:Subcutaneous Fat / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D001786:Blood Glucose; D015850:Interleukin-6; D011506:Proteins; D014409:Tumor Necrosis Factor-alpha; D012313:RNA; D002097:C-Reactive Protein; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human