Subcutaneous and visceral adipose tissue FTO gene expression and adiposity, insulin action, glucose metabolism, and inflammatory adipokines in type 2 diabetes mellitus and in health.
BACKGROUND
FTO gene variants are linked to obesity. We tested for site-specific differences in FTO gene expression in subcutaneous and visceral adipose tissue (SAT and VAT, respectively) from individuals with and without type 2 diabetes mellitus (T2D) and the relationships between fasting glucose, in vivo insulin action, and measures of adiposity with FTO gene expression in adipose tissue.


METHODS
Paired subcutaneous and visceral fat were excised at elective surgery in n = 16 subjects (six with T2D, age-matched). Metabolic parameters were measured in fasted state; body composition by dual-energy X-ray absorptiometry; and insulin action by hyperinsulinemic euglycemic clamp. Adipose tissue mRNA gene expression was determined by quantitative RT-PCR.


RESULTS
Subjects with T2D had SAT and VAT FTO mRNA expression similar to controls. There was no depot specificity between SAT and VAT FTO mRNA expression. Insulin action did not relate to SAT or VAT FTO mRNA expression. SAT FTO mRNA expression was related to fasting glucose and waist circumference only. SAT and VAT FTO mRNA expression was not related to direct measures of total or central abdominal adiposity. SAT FTO mRNA expression was related to SAT tumor necrosis factor-alpha and nuclear factor-kappaB mRNA expression.


CONCLUSIONS
FTO gene expression is not increased in SAT and VAT in T2D and does not relate to insulin action. The links between FTO and metabolic complications of diabetes require further elucidation.
Samaras
Katherine
K
Department of Endocrinology, St. Vincent's Hospital, 384 Victoria Street, Darlinghurst, NSW 2010, Australia. k.samaras@garvan.org.au
Botelho
Natalia K
NK
Chisholm
Donald J
DJ
Lord
Reginald V
RV
D000368:Aged; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D015897:Comorbidity; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D015309:Glucose Clamp Technique; D006801:Humans; D007328:Insulin / Q000378:metabolism; D050152:Intra-Abdominal Fat / Q000378:metabolism / Q000502:physiology / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D009765:Obesity / Q000453:epidemiology / Q000235:genetics*; D011506:Proteins / Q000378:metabolism*; D050151:Subcutaneous Fat / Q000378:metabolism / Q000503:physiopathology*; D055105:Waist Circumference
D007328:Insulin; D016328:NF-kappa B; D011506:Proteins; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human