title: The expression of FTO in human adipose tissue is influenced by fat depot, adiposity, and insulin sensitivity.
abstract: OBJECTIVE
  The fat mass and obesity associated (FTO) gene is related to obesity, but the regulation of FTO expression in adipose tissue is not fully understood. We investigated FTO expression in paired subcutaneous and omental adipose tissues (SAT and OAT) from healthy women undergoing gynecological surgeries, and its relation with adiposity and insulin sensitivity.
  
  
  METHODS
  FTO expression in SAT of type 2 diabetic patients treated or not with Rosiglitazone was also compared.
  
  
  RESULTS
  Both the mRNA and protein levels of FTO were higher in OAT from women than in SAT. Only OAT FTO protein levels negatively correlated with BMI and body fat mass, whereas SAT FTO mRNA levels were negatively correlated with subcutaneous fat deposition. In addition, SAT FTO mRNA and protein levels were increased in insulin resistant women (high HOMA) compared to insulin sensitive women (low HOMA), whereas OAT FTO expression was not different between these two subgroups. Interestingly, FTO mRNA levels were increased in SAT of type 2 diabetic patients, and treatment of diabetics with Rosiglitazone improved insulin sensitivity and reduced SAT FTO mRNA levels. Lastly, FTO expression was transiently increased in the early phase of 3T3-L1 cell differentiation, which coincides with the induction of PPARγ2 expression. However, partial reduction of FTO did not impact PPARγ2 expression and adipocyte differentiation.
  
  
  CONCLUSIONS
  Therefore, FTO gene expression is higher in OAT than in SAT in lean to moderately obese women. OAT FTO expression is associated with adiposity, whereas SAT FTO expression is associated with insulin sensitivity. These associations are independent of an effect of FTO on adipocyte differentiation.
authors.affiliation: INSERM UMR-1060, CarMeN Laboratory, Lyon 1 University, Charles Merieux Lyon-Sud Medical School, Lyon, F-69003, France.
authors.forename: Amélie
authors.initials: A
authors.lastname: Bravard
authors.forename: Alain
authors.initials: A
authors.lastname: Veilleux
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Disse
authors.forename: Martine
authors.initials: M
authors.lastname: Laville
authors.forename: Hubert
authors.initials: H
authors.lastname: Vidal
authors.forename: André
authors.initials: A
authors.lastname: Tchernof
authors.forename: Jennifer
authors.initials: J
authors.lastname: Rieusset
mesh_terms: D041721:3T3-L1 Cells; D050156:Adipogenesis / Q000235:genetics; D000273:Adipose Tissue / Q000378:metabolism*; D050154:Adiposity / Q000502:physiology*; D000328:Adult; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D000818:Animals; D015992:Body Mass Index; D002454:Cell Differentiation; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D051379:Mice; D008875:Middle Aged; D009765:Obesity / Q000235:genetics / Q000378:metabolism; D009852:Omentum / Q000378:metabolism; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology
chemical_list: D007004:Hypoglycemic Agents; D047495:PPAR gamma; D011506:Proteins; D012333:RNA, Messenger; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human