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Fas activates lipolysis in a Ca2+-CaMKII-dependent manner in 3T3-L1 adipocytes


Rapold, Reto A; Wueest, Stephan; Knoepfel, Adrian; Schoenle, Eugen J; Konrad, Daniel (2013). Fas activates lipolysis in a Ca2+-CaMKII-dependent manner in 3T3-L1 adipocytes. Journal of Lipid Research, 54(1):63-70.

Abstract

Fas (CD95) is a member of the tumor necrosis factor (TNF) receptor superfamily and plays a crucial role in the induction of apoptosis. However, like TNF, Fas can induce non-apoptotic signaling pathways. We previously demonstrated that mice lacking Fas specifically in adipocytes are partly protected from diet-induced insulin resistance, potentially via decreased delivery of fatty acids to the liver as manifested by lower total liver ceramide content. In the present study we aimed to delineate the signaling pathway involved in Fas-mediated adipocyte lipid mobilization. Treatment of differentiated 3T3-L1 adipocytes with membrane-bound Fas ligand (FasL) significantly increased lipolysis after 12 hours without inducing apoptosis. In parallel, Fas activation increased phosphorylation of ERK1/2 and FasL-induced lipolysis was blunted in the presence of the ERK-inhibitor U0126 or in ERK1/2-depleted adipocytes. Furthermore, Fas activation increased phosphorylation of the Ca2+/calmodulin-dependent protein kinases II (CaMKII) and blocking of the CaMKII-pathway (either by the Ca2+ chelator BAPTA or by the CaMKII inhibitor KN62) blunted FasL-induced ERK1/2 phosphorylation and glycerol release. In conclusion, we propose a novel role for CaMKII in promoting lipolysis in adipocytes.

Fas (CD95) is a member of the tumor necrosis factor (TNF) receptor superfamily and plays a crucial role in the induction of apoptosis. However, like TNF, Fas can induce non-apoptotic signaling pathways. We previously demonstrated that mice lacking Fas specifically in adipocytes are partly protected from diet-induced insulin resistance, potentially via decreased delivery of fatty acids to the liver as manifested by lower total liver ceramide content. In the present study we aimed to delineate the signaling pathway involved in Fas-mediated adipocyte lipid mobilization. Treatment of differentiated 3T3-L1 adipocytes with membrane-bound Fas ligand (FasL) significantly increased lipolysis after 12 hours without inducing apoptosis. In parallel, Fas activation increased phosphorylation of ERK1/2 and FasL-induced lipolysis was blunted in the presence of the ERK-inhibitor U0126 or in ERK1/2-depleted adipocytes. Furthermore, Fas activation increased phosphorylation of the Ca2+/calmodulin-dependent protein kinases II (CaMKII) and blocking of the CaMKII-pathway (either by the Ca2+ chelator BAPTA or by the CaMKII inhibitor KN62) blunted FasL-induced ERK1/2 phosphorylation and glycerol release. In conclusion, we propose a novel role for CaMKII in promoting lipolysis in adipocytes.

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7 citations in Scopus®
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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Children's Hospital Zurich > Medical Clinic
04 Faculty of Medicine > Center for Integrative Human Physiology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2013
Deposited On:01 Nov 2012 14:34
Last Modified:05 Apr 2016 16:03
Publisher:American Society for Biochemistry and Molecular Biology
ISSN:0022-2275
Additional Information:This research was originally published in The Journal of Lipid Research. Reto A. Rapold, Sephan Wueest, Adrian Knoepfel, Eugen J. Schoenle, and Daniel Konrad: Fas activates lipolysis in a Ca2+-CaMKII-dependent manner in 3T3-L1 adipocytes. 2013 54:(1) 63-70. © the American Society for Biochemistry and Molecular Biology.
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1194/jlr.M028035
PubMed ID:23089915
Permanent URL: https://doi.org/10.5167/uzh-66136

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