title: Relationship between site-specific HSL phosphorylation and adipocyte lipolysis in obese women.
abstract: OBJECTIVE
  In fat cells of obese humans, basal lipolysis is increased but catecholamine-stimulated lipolysis is blunted. This is linked to decreased expression of hormone-sensitive lipase (HSL). Upon stimulation by cAMP, HSL is phosphorylated at several serine residues (P-Ser(552), P-Ser(649) and P-Ser(650)) leading to enzymatic activation. In contrast, P-Ser(554) prevents phosphorylation at Ser(552) and is thus considered an inactivating site. We hypothesized that differences in HSL phosphorylation could be linked to disturbed adipocyte lipolysis in obesity.
  
  
  METHODS
  Phosphorylation at Ser(552), Ser(554), Ser(650) as well as total HSL and adipose triglyceride lipase (ATGL) protein expression were assessed by Western blot in subcutaneous adipose tissue samples of 32 obese women. Basal and stimulated lipolysis in isolated fat cells were correlated to phosphorylation levels.
  
  
  RESULTS
  While there was no correlation between basal lipolysis and P-Ser(650) or P-Ser(554), there was a negative correlation with P-Ser(552) (r = 0.39; p < 0.05). In contrast, only P-Ser(554) was strongly and negatively correlated with noradrenaline- (r = -0.50; p < 0.01) and dibutyryl cAMP-stimulated (r = -0.45; p < 0.05) lipolysis. There were no significant correlations between any measure of lipolysis and total levels of HSL and ATGL.
  
  
  CONCLUSIONS
  In contrast to total HSL and ATGL levels, phosphorylation at Ser(554) and Ser(552), but not at Ser(650), may differentially predict adipocyte lipolysis in vitro. Posttranslational modifications of HSL may therefore constitute an important regulator of adipocyte lipolysis, at least in adipose tissue of obese women. Whether this is also relevant in lean individuals remains to be demonstrated.
authors.affiliation: Department of Medicine Huddinge, Lipid Laboratory, Karolinska Institutet, NVS, Karolinska University Hospital, Stockholm, Sweden. Silvia.Lorente-Cebrian@ki.se
authors.forename: Silvia
authors.initials: S
authors.lastname: Lorente-Cebrián
authors.forename: Agné
authors.initials: A
authors.lastname: Kulyté
authors.forename: Per
authors.initials: P
authors.lastname: Hedén
authors.forename: Erik
authors.initials: E
authors.lastname: Näslund
authors.forename: Peter
authors.initials: P
authors.lastname: Arner
authors.forename: Mikael
authors.initials: M
authors.lastname: Rydén
mesh_terms: D017667:Adipocytes / Q000378:metabolism*; D000328:Adult; D000242:Cyclic AMP / Q000494:pharmacology; D005260:Female; D006801:Humans; D008049:Lipase / Q000378:metabolism*; D008066:Lipolysis / Q000502:physiology*; D008875:Middle Aged; D009638:Norepinephrine / Q000494:pharmacology; D009765:Obesity / Q000378:metabolism*; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D012694:Serine / Q000378:metabolism*; D002787:Sterol Esterase / Q000378:metabolism*
chemical_list: D012694:Serine; D000242:Cyclic AMP; D002787:Sterol Esterase; D008049:Lipase; D009638:Norepinephrine