title: Adipose triglyceride lipase and hormone-sensitive lipase protein expression is decreased in the obese insulin-resistant state.
abstract: OBJECTIVE
  Obesity is associated with increased triacylglycerol (TAG) storage in adipose tissue and insulin resistance. The mobilization of stored TAG is mediated by hormone-sensitive lipase (HSL) and the recently discovered adipose triglyceride lipase (ATGL). The aim of the present study was to examine whether ATGL and HSL mRNA and protein expression are altered in insulin-resistant conditions. In addition, we investigated whether a possible impaired expression could be reversed by a period of weight reduction.
  
  
  METHODS
  Adipose tissue biopsies were taken from obese subjects (n = 44) with a wide range of insulin resistance, before and just after a 10-wk hypocaloric diet. ATGL and HSL protein and mRNA expression was determined by Western blot and quantitative RT-PCR, respectively.
  
  
  RESULTS
  Fasting insulin levels and the degree of insulin resistance (using the homeostasis model assessment index for insulin resistance) were negatively correlated with ATGL and HSL protein expression, independent of age, gender, fat cell size, and body composition. Both mRNA and protein levels of ATGL and HSL were reduced in insulin-resistant compared with insulin-sensitive subjects (P < 0.05). Weight reduction significantly decreased ATGL and HSL mRNA and protein expression. A positive correlation between the decrease in leptin and the decrease in ATGL protein level after weight reduction was observed. Finally, ATGL and HSL mRNA and protein levels seem to be highly correlated, indicating a tight coregulation and transcriptional control.
  
  
  CONCLUSIONS
  In obese subjects, insulin resistance and hyperinsulinemia are strongly associated with ATGL and HSL mRNA and protein expression, independent of fat mass. Data on weight reduction indicated that also other factors (e.g. leptin) relate to ATGL and HSL protein expression.
authors.affiliation: Department of Human Biology, Maastricht University, Maastricht, The Netherlands. j.jocken@hb.unimaas.nl
authors.forename: Johan W E
authors.initials: JW
authors.lastname: Jocken
authors.forename: Dominique
authors.initials: D
authors.lastname: Langin
authors.forename: Egbert
authors.initials: E
authors.lastname: Smit
authors.forename: Wim H M
authors.initials: WH
authors.lastname: Saris
authors.forename: Carine
authors.initials: C
authors.lastname: Valle
authors.forename: Gabby B
authors.initials: GB
authors.lastname: Hul
authors.forename: Cecilia
authors.initials: C
authors.lastname: Holm
authors.forename: Peter
authors.initials: P
authors.lastname: Arner
authors.forename: Ellen E
authors.initials: EE
authors.lastname: Blaak
mesh_terms: D000273:Adipose Tissue / Q000201:enzymology* / Q000473:pathology; D000328:Adult; D001706:Biopsy; D004038:Diet, Reducing; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D006946:Hyperinsulinism / Q000178:diet therapy / Q000378:metabolism / Q000473:pathology; D007333:Insulin Resistance / Q000502:physiology*; D008049:Lipase / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000178:diet therapy / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D012044:Regression Analysis; D002787:Sterol Esterase / Q000235:genetics / Q000378:metabolism*; D015431:Weight Loss / Q000502:physiology
chemical_list: D012333:RNA, Messenger; D002787:Sterol Esterase; D008049:Lipase