title: Munc18c in adipose tissue is downregulated in obesity and is associated with insulin.
abstract: OBJECTIVE
  Munc18c is associated with glucose metabolism and could play a relevant role in obesity. However, little is known about the regulation of Munc18c expression. We analyzed Munc18c gene expression in human visceral (VAT) and subcutaneous (SAT) adipose tissue and its relationship with obesity and insulin.
  
  
  METHODS
  We evaluated 70 subjects distributed in 12 non-obese lean subjects, 23 overweight subjects, 12 obese subjects and 23 nondiabetic morbidly obese patients (11 with low insulin resistance and 12 with high insulin resistance).
  
  
  RESULTS
  The lean, overweight and obese persons had a greater Munc18c gene expression in adipose tissue than the morbidly obese patients (p<0.001). VAT Munc18c gene expression was predicted by the body mass index (B = -0.001, p = 0.009). In SAT, no associations were found by different multiple regression analysis models. SAT Munc18c gene expression was the main determinant of the improvement in the HOMA-IR index 15 days after bariatric surgery (B = -2148.4, p = 0.038). SAT explant cultures showed that insulin produced a significant down-regulation of Munc18c gene expression (p = 0.048). This decrease was also obtained when explants were incubated with liver X receptor alpha (LXRα) agonist, either without (p = 0.038) or with insulin (p = 0.050). However, Munc18c gene expression was not affected when explants were incubated with insulin plus a sterol regulatory element-binding protein-1c (SREBP-1c) inhibitor (p = 0.504).
  
  
  CONCLUSIONS
  Munc18c gene expression in human adipose tissue is down-regulated in morbid obesity. Insulin may have an effect on the Munc18c expression, probably through LXRα and SREBP-1c.
authors.affiliation: Endocrinology and Diabetes Unit, Joan XXIII University Hospital, IISPV, Universitat Rovira i Virgili, Tarragona, Spain.
authors.forename: Lourdes
authors.initials: L
authors.lastname: Garrido-Sanchez
authors.forename: Xavier
authors.initials: X
authors.lastname: Escote
authors.forename: Leticia
authors.initials: L
authors.lastname: Coin-Aragüez
authors.forename: Jose Carlos
authors.initials: JC
authors.lastname: Fernandez-Garcia
authors.forename: Rajaa
authors.initials: R
authors.lastname: El Bekay
authors.forename: Joan
authors.initials: J
authors.lastname: Vendrell
authors.forename: Eduardo
authors.initials: E
authors.lastname: Garcia-Fuentes
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Tinahones
mesh_terms: D000328:Adult; D000368:Aged; D015992:Body Mass Index; D015536:Down-Regulation; D005260:Female; D015870:Gene Expression; D005786:Gene Expression Regulation; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D050152:Intra-Abdominal Fat / Q000378:metabolism*; D000071518:Liver X Receptors; D008297:Male; D008875:Middle Aged; D051938:Munc18 Proteins / Q000235:genetics / Q000378:metabolism*; D009767:Obesity, Morbid / Q000378:metabolism*; D057093:Orphan Nuclear Receptors / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism; D051780:Sterol Regulatory Element Binding Protein 1 / Q000378:metabolism; D050507:Subcutaneous Fat, Abdominal / Q000378:metabolism*; D046509:Tissue Culture Techniques
chemical_list: D007328:Insulin; D000071518:Liver X Receptors; D051938:Munc18 Proteins; C000605213:NR1H3 protein, human; D057093:Orphan Nuclear Receptors; D047495:PPAR gamma; D051780:Sterol Regulatory Element Binding Protein 1