Hormone-sensitive lipase expression and activity in relation to lipolysis in human fat cells.
Hormone-sensitive lipase (HSL) catalyzes the rate-limiting step in adipocyte lipolysis. The activity of HSL is thought to be primarily regulated by reversible phosphorylation. However, the regulation of HSL activity by pre-translational mechanisms has been poorly studied. The present studies were undertaken to explore the relationship between the levels of HSL protein and mRNA expressions and the lipolytic capacity. The study was performed in human abdominal subcutaneous adipocytes with identical sizes but having either a high (HL) or low (LL) lipolytic capacity (n = 16). Basal and maximal lipolysis induced by catecholamines, an adenylyl cyclase activator forskolin, and a cyclic AMP analogue dibutyryl cAMP were 50% lower in LL- in comparison with HL-fat cells (P < 0.05 or better). No differences in drug sensitivity were found. HSL activity and quantity were about 50% lower in LL- compared with HL-fat cells (P < 0.05). Moreover, the mRNA ratio between HSL and gamma-actin was 35% lower in LL- compared with HL-fat cells (P < 0.05). There was a strong linear correlation between the protein and enzymatic HSL measurements (r2 = 0.91). In addition, the maximum lipolytic capacity was significantly correlated with HSL activity (r2 = 0.75) and HSL protein amount (r2 = 0.64). It is concluded that hormone-sensitive lipase (HSL) expression, measured either as total HSL protein by Western blot analysis or as total amount of activatable HSL enzyme, is a major determinant of the maximum lipolytic capacity of human fat cells. In addition, HSL protein expression is at least, in part, determined by HSL mRNA expression.
Department of Medicine, Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden.
V
V
Large
P
P
Arner
S
S
Reynisdottir
J
J
Grober
V
V
Van Harmelen
C
C
Holm
D
D
Langin
D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D048429:Cell Size; D005260:Female; D014644:Genetic Variation; D006801:Humans; D007120:Immunochemistry; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D008066:Lipolysis / Q000187:drug effects; D008297:Male; D008970:Molecular Weight; D009765:Obesity / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D002787:Sterol Esterase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D012333:RNA, Messenger; D002787:Sterol Esterase; D007545:Isoproterenol