Adipose triglyceride lipase and hormone-sensitive lipase protein expression is decreased in the obese insulin-resistant state.
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.
Jocken
Johan W E
JW
Department of Human Biology, Maastricht University, Maastricht, The Netherlands. j.jocken@hb.unimaas.nl
Langin
Dominique
D
Smit
Egbert
E
Saris
Wim H M
WH
Valle
Carine
C
Hul
Gabby B
GB
Holm
Cecilia
C
Arner
Peter
P
Blaak
Ellen E
EE
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
D012333:RNA, Messenger; D002787:Sterol Esterase; D008049:Lipase