The presence of a catalytically inactive form of hormone-sensitive lipase is associated with decreased lipolysis in abdominal subcutaneous adipose tissue of obese subjects.
Hormone-sensitive lipase (HSL)-L is a key enzyme in the mobilization of fatty acids from triglyceride stores in adipocytes. A shorter variant of HSL (HSL-S) was detected in humans. This one is generated through in-frame skipping of exon 6 during the processing of HSL mRNA and results in a protein devoid of lipase activity. The role of HSL-S is unknown. The aims of this study were to identify both HSL variants in adipose tissue biopsies and to determine if the presence of HSL-S is correlated to the lipolytic capacity of adipocytes. The study was performed in human abdominal subcutaneous adipocytes from two groups of seven obese subjects. In the group of subjects with both HSL proteins (L+S) group, two immunoreactive bands (80 and 88 kDa) were detected, whereas only the 88-kDa protein was detected in the group with only the wild-type HSL-protein (L group). In the L+S group, the HSL activity was 20% lower (P < 0.05) and the (S/S(+)) HSL mRNA ratio was twofold higher than in the L group (P < 0.05). The maximally lipolytic capacities measured from isolated adipocytes incubated with norepinephrine or other lipolytic agents were 40% lower in the L+S group (P < 0.05). These results suggest that the presence of the truncated HSL protein is associated with an impaired adipocyte lipolysis.
Ray
Hind
H
Institut National de la Santé et de la Recherche Medicale (INSERM) 499, Faculté de Médecine Laennec, Rue Paradin, 69372 Lyon, France.
Beylot
Michel
M
Arner
Peter
P
Larrouy
Dominique
D
Langin
Dominique
D
Holm
Cecilia
C
Large
Valérie
V
D000005:Abdomen; D000273:Adipose Tissue / Q000201:enzymology / Q000503:physiopathology*; D000328:Adult; D001483:Base Sequence; D015992:Body Mass Index; D002384:Catalysis; D018076:DNA, Complementary / Q000235:genetics; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005260:Female; D014644:Genetic Variation; D006801:Humans; D007700:Kinetics; D008066:Lipolysis / Q000502:physiology*; D008297:Male; D009765:Obesity / Q000201:enzymology / Q000503:physiopathology*; D012333:RNA, Messenger / Q000235:genetics; D012044:Regression Analysis; D002787:Sterol Esterase / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D014280:Triglycerides / Q000378:metabolism
D018076:DNA, Complementary; D005230:Fatty Acids, Nonesterified; D012333:RNA, Messenger; D014280:Triglycerides; D002787:Sterol Esterase