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Measuring the Rate of Lipolysis in Ex Vivo Murine Adipose Tissue and Primary Preadipocytes Differentiated In Vitro
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Fas activates lipolysis in a Ca2+-CaMKII-dependent manner in 3T3-L1 adipocytes

Reto A Rapold1, Stephan Wueest, Adrian Knoepfel

  • 1Division of Pediatric Endocrinology and Diabetology, University Children's Hospital, CH-8032 Zurich, Switzerland.

Journal of Lipid Research
|October 24, 2012
PubMed

Insights

Fas ligand activates Ca2+/calmodulin-dependent protein kinases II (CaMKII) in fat cells, promoting lipid breakdown (lipolysis) without causing cell death. This reveals a new pathway for regulating fat metabolism.

Area of Science:

  • Cell Biology
  • Metabolic Signaling
  • Endocrinology

Background:

  • Fas (CD95) is a TNF receptor superfamily member involved in apoptosis and non-apoptotic signaling.
  • Previous studies linked adipocyte-specific Fas deficiency to protection from diet-induced insulin resistance.
  • The precise signaling cascade for Fas-mediated adipocyte lipid mobilization remained unclear.

Purpose of the Study:

  • To elucidate the signaling pathway mediating Fas-induced lipolysis in adipocytes.
  • To identify key molecular players in Fas-activated lipid mobilization.

Main Methods:

  • Treatment of differentiated 3T3-L1 adipocytes with membrane-bound Fas ligand (FasL).
  • Assessment of lipolysis, apoptosis, and protein phosphorylation (ERK1/2, CaMKII).
  • Use of specific inhibitors (U0126, KN62) and depletion techniques (siRNA) to block signaling pathways.

Main Results:

  • FasL treatment increased adipocyte lipolysis without inducing apoptosis.
  • Fas activation led to ERK1/2 phosphorylation, which was essential for lipolysis.
  • FasL also increased CaMKII phosphorylation, and CaMKII inhibition blocked ERK1/2 phosphorylation and lipolysis.

Conclusions:

  • Fas activation promotes adipocyte lipolysis via a pathway involving ERK1/2.
  • Ca2+/calmodulin-dependent protein kinases II (CaMKII) acts upstream of ERK1/2 in this pathway.
  • CaMKII plays a novel role in promoting lipolysis in adipocytes, independent of apoptosis.

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