Metformin counters both lipolytic/inflammatory agents-decreased hormone sensitive lipase phosphorylation at Ser-554 and -induced lipolysis in human adipocytes

Arch Physiol Biochem. 2011 Oct;117(4):209-14. doi: 10.3109/13813455.2010.550925. Epub 2011 Feb 22.

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.

Conclusion: Phosphorylation of HSL at Ser-554 inversely correlates with lipolysis and HSL phosphorylation at Ser552 in human adipocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-3-isobutylxanthine / adverse effects
  • 1-Methyl-3-isobutylxanthine / pharmacology
  • Adipocytes / drug effects*
  • Adipocytes / metabolism
  • Adult
  • Aged
  • Colforsin / adverse effects
  • Colforsin / pharmacology
  • Female
  • Humans
  • Hypoglycemic Agents* / pharmacology
  • Hypoglycemic Agents* / therapeutic use
  • Inflammation / drug therapy
  • Interleukin-1beta / adverse effects
  • Interleukin-1beta / pharmacology
  • Isoproterenol / adverse effects
  • Isoproterenol / pharmacology
  • Lipolysis / drug effects*
  • Lipopolysaccharides / adverse effects
  • Lipopolysaccharides / pharmacology
  • Male
  • Metformin* / pharmacology
  • Metformin* / therapeutic use
  • Middle Aged
  • Phosphorylation / drug effects*
  • Primary Cell Culture
  • Serine / metabolism*
  • Sterol Esterase / metabolism*
  • Tumor Necrosis Factor-alpha / adverse effects
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • Hypoglycemic Agents
  • IL1B protein, human
  • Interleukin-1beta
  • Lipopolysaccharides
  • Tumor Necrosis Factor-alpha
  • Colforsin
  • Serine
  • Metformin
  • Sterol Esterase
  • Isoproterenol
  • 1-Methyl-3-isobutylxanthine