Decreased expression and function of adipocyte hormone-sensitive lipase in subcutaneous fat cells of obese subjects.
Decreased lipolytic effect of catecholamines in adipose tissue has repeatedly been demonstrated in obesity and may be a cause of excess accumulation of body fat. However, the mechanisms behind this lipolysis defect are unclear. The role of hormone-sensitive lipase was examined using abdominal subcutaneous adipocytes from 34 obese drug-free and otherwise healthy males or females and 14 non-obese control subjects. The enzyme catalyzes the rate-limiting step of the lipolysis pathway. The maximum lipolytic capacity of fat cells was significantly decreased in obesity when measured using either a non-selective beta-adrenergic receptor agonist (isoprenaline) or a phosphodiesterase resistant cyclic AMP analogue (dibutyryl cyclic AMP). Likewise, enzyme activity, protein expression, and mRNA of hormone-sensitive lipase were significantly decreased in adipocytes of obese subjects. The findings were not influenced by age or gender. The data suggest that a decreased expression of hormone-sensitive lipase in subcutaneous fat cells, which in turn causes decreased enzyme function and impaired lipolytic capacity of adipocytes, is present in obesity. Impaired expression of the hormone-sensitive lipase gene might at least in part explain the enzyme defect.
Large
V
V
Department of Medicine, Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden.
Reynisdottir
S
S
Langin
D
D
Fredby
K
K
Klannemark
M
M
Holm
C
C
Arner
P
P
D000273:Adipose Tissue / Q000737:chemistry / Q000166:cytology / Q000201:enzymology*; D000328:Adult; D000367:Age Factors; D000368:Aged; D015992:Body Mass Index; D001837:Body Weights and Measures; D048429:Cell Size; D005260:Female; D005786:Gene Expression Regulation; D005990:Glycerol / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000097:blood; D008066:Lipolysis / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009765:Obesity / Q000201:enzymology* / Q000209:etiology / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D012737:Sex Factors; D002787:Sterol Esterase / Q000032:analysis / Q000235:genetics*
D007328:Insulin; D012333:RNA, Messenger; D002787:Sterol Esterase; D005990:Glycerol