Universität zu Köln

Turpin-Nolan, Sarah M., Hammerschmidt, Philipp, Chen, Weiyi, Jais, Alexander ORCID: 0000-0002-9897-4983, Timper, Katharina, Awazawa, Motoharu, Brodesser, Susanne and Bruening, Jens C. (2019). CerS1-Derived C-18:0 Ceramide in Skeletal Muscle Promotes Obesity-Induced Insulin Resistance. Cell Reports, 26 (1). S. 1 - 18. CAMBRIDGE: CELL PRESS. ISSN 2211-1247

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Abstract

Skeletal muscle accumulates ceramides in obesity, which contribute to the development of obesity-associated insulin resistance. However, it remained unclear which distinct ceramide species in this organ contributes to instatement of systemic insulin resistance. Here, ceramide profiling of high-fat diet (HFD)-fed animals revealed increased skeletal muscle C-18:0 ceramide content, concomitant with increased expression of ceramide synthase (CerS)1. Mice lacking CerS1, either globally or specifically in skeletal muscle (CerS1 Delta(SkM)), exhibit reduced muscle C-18:0 ceramide content and significant improvements in systemic glucose homeostasis. CerS1 Delta(SkM) mice exhibit improved insulin-stimulated suppression of hepatic glucose production, and lack of CerS1 in skeletal muscle improves systemic glucose homeostasis via increased release of Fgf21 from skeletal muscle. In contrast, muscle-specific deficiency of C-16:0 ceramide-producing CerS5 and CerS6 failed to protect mice from obesity-induced insulin resistance. Collectively, these results reveal the tissue-specific function of distinct ceramide species during the development of obesity-associated insulin resistance.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Turpin-Nolan, Sarah M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hammerschmidt, Philipp UNSPECIFIED UNSPECIFIED UNSPECIFIED Chen, Weiyi UNSPECIFIED UNSPECIFIED UNSPECIFIED Jais, Alexander UNSPECIFIED orcid.org/0000-0002-9897-4983 UNSPECIFIED Timper, Katharina UNSPECIFIED UNSPECIFIED UNSPECIFIED Awazawa, Motoharu UNSPECIFIED UNSPECIFIED UNSPECIFIED Brodesser, Susanne UNSPECIFIED UNSPECIFIED UNSPECIFIED Bruening, Jens C. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-159640
DOI:	10.1016/j.celrep.2018.12.031
Journal or Publication Title:	Cell Reports
Volume:	26
Number:	1
Page Range:	S. 1 - 18
Date:	2019
Publisher:	CELL PRESS
Place of Publication:	CAMBRIDGE
ISSN:	2211-1247
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language DEFICIENCY; METABOLISM; INHIBITION; EXERCISE; ENERGY; FGF21 Multiple languages Cell Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/15964