title: Metformin counters both lipolytic/inflammatory agents-decreased hormone sensitive lipase phosphorylation at Ser-554 and -induced lipolysis in human adipocytes.
abstract: OBJECTIVE
  To study the effects of metformin on lipolysis and hormone sensitive lipase (HSL) phosphorylation in human adipocytes treated with lipolytic and inflammatory agents.
  
  
  METHODS
  Lipolysis and phosphorylation status of HSL were assessed in subcutaneous pre-adipocytes surgically isolated from patients and differentiated into mature adipocytes in vitro.
  
  
  RESULTS
  Stimulation for 1 h with forskolin, isoproterenol and IBMX or stimulation for 24 h with LPS, IL-1β and TNF-α increased lipolysis (p < 0.05 vs. basal). The phosphorylation of HSL at Ser-554 was decreased while the Ser-552 phosphorylation was increased. Pre-incubation with metformin (24 h, 1 mM) inhibited forskolin-, isoproterenol-, IBMX-, LPS-, IL-1β- and TNF-α-induced glycerol release and prevented p(Ser554)HSL decrease and p(Ser-552)HSL increase due to lipolytic and inflammatory agents. AMPKα1 is involved in metformin-induced HSL phosphorylation at Ser-552.
  
  
  CONCLUSIONS
  Phosphorylation of HSL at Ser-554 inversely correlates with lipolysis and HSL phosphorylation at Ser552 in human adipocytes.
authors.affiliation: University Hospital Basel, Department of Biomedicine, Switzerlands. jean.grisouard@unibas.ch
authors.forename: Jean
authors.initials: J
authors.lastname: Grisouard
authors.forename: Katharina
authors.initials: K
authors.lastname: Timper
authors.forename: Elisa
authors.initials: E
authors.lastname: Bouillet
authors.forename: Tanja
authors.initials: T
authors.lastname: Radimerski
authors.forename: Kaethi
authors.initials: K
authors.lastname: Dembinski
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Frey
authors.forename: Ralph
authors.initials: R
authors.lastname: Peterli
authors.forename: Henryk
authors.initials: H
authors.lastname: Zulewski
authors.forename: Ulrich
authors.initials: U
authors.lastname: Keller
authors.forename: Beat
authors.initials: B
authors.lastname: Müller
authors.forename: Mirjam
authors.initials: M
authors.lastname: Christ-Crain
mesh_terms: D015056:1-Methyl-3-isobutylxanthine / Q000009:adverse effects / Q000494:pharmacology; D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism; D000328:Adult; D000368:Aged; D005576:Colforsin / Q000009:adverse effects / Q000494:pharmacology; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use; D007249:Inflammation / Q000188:drug therapy; D053583:Interleukin-1beta / Q000009:adverse effects / Q000494:pharmacology; D007545:Isoproterenol / Q000009:adverse effects / Q000494:pharmacology; D008066:Lipolysis / Q000187:drug effects*; D008070:Lipopolysaccharides / Q000009:adverse effects / Q000494:pharmacology; D008297:Male; D008687:Metformin / Q000494:pharmacology / Q000627:therapeutic use; D008875:Middle Aged; D010766:Phosphorylation / Q000187:drug effects*; D061251:Primary Cell Culture; D012694:Serine / Q000378:metabolism*; D002787:Sterol Esterase / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000009:adverse effects / Q000494:pharmacology
chemical_list: D007004:Hypoglycemic Agents; C508585:IL1B protein, human; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D005576:Colforsin; D012694:Serine; D008687:Metformin; D002787:Sterol Esterase; D007545:Isoproterenol; D015056:1-Methyl-3-isobutylxanthine