Universität zu Köln

Lindner, Angie, Marbach, Felix, Tschernitz, Sebastian, Ortner, Christine, Berneburg, Mark, Felthaus, Oliver, Prantl, Lukas, Kye, Min Jeong ORCID: 0000-0002-1323-7256, Rappl, Gunter, Altmueller, Janine, Thieles, Holger, Schreml, Stephan ORCID: 0000-0002-2820-1942 and Schreml, Julia (2019). Calcyphosine-like (CAPSL) is regulated in Multiple Symmetric Lipomatosis and is involved in Adipogenesis. Sci Rep, 9. LONDON: NATURE PUBLISHING GROUP. ISSN 2045-2322

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Abstract

Little is known on the causes and pathogenesis of the adipose tissue disorder (familial) Multiple Symmetric Lipomatosis (MSL). In a four-generation MSL-family, we performed whole exome sequencing (WES) in 3 affected individuals and 1 obligate carrier and identified Calcyphosine-like (CAPSL) as the most promising candidate gene for this family. Screening of 21 independent patients excluded CAPSL coding sequence variants as a common monogenic cause, but using immunohistochemistry we found that CAPSL was down-regulated in adipose tissue not only from the index patient but also in 10 independent sporadic MSL-patients. This suggests that CAPSL is regulated in sporadic MSL irrespective of the underlying genetic/multifactorial cause. Furthermore, we cultivated pre-adipocytes from MSL-patients and generated 3T3-L1-based Capsl knockout and overexpressing cell models showing altered autophagy, adipogenesis, lipogenesis and Sirtuin-1 (SIRT1) expression. CAPSL seems to be involved in adipocyte biology and perturbation of autophagy is a potential mechanism in the pathogenesis of MSL. Downregulation of CAPSL and upregulation of UCP1 were common features in MSL fat while the known MSL genes MFN2 and LIPE did not show consistent alterations. CAPSL immunostainings could serve as first diagnostic tools in MSL clinical care with a potential to improve time to diagnosis and healthcare options.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Lindner, Angie UNSPECIFIED UNSPECIFIED UNSPECIFIED Marbach, Felix UNSPECIFIED UNSPECIFIED UNSPECIFIED Tschernitz, Sebastian UNSPECIFIED UNSPECIFIED UNSPECIFIED Ortner, Christine UNSPECIFIED UNSPECIFIED UNSPECIFIED Berneburg, Mark UNSPECIFIED UNSPECIFIED UNSPECIFIED Felthaus, Oliver UNSPECIFIED UNSPECIFIED UNSPECIFIED Prantl, Lukas UNSPECIFIED UNSPECIFIED UNSPECIFIED Kye, Min Jeong UNSPECIFIED orcid.org/0000-0002-1323-7256 UNSPECIFIED Rappl, Gunter UNSPECIFIED UNSPECIFIED UNSPECIFIED Altmueller, Janine UNSPECIFIED UNSPECIFIED UNSPECIFIED Thieles, Holger UNSPECIFIED UNSPECIFIED UNSPECIFIED Schreml, Stephan UNSPECIFIED orcid.org/0000-0002-2820-1942 UNSPECIFIED Schreml, Julia UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-137900
DOI:	10.1038/s41598-019-44382-1
Journal or Publication Title:	Sci Rep
Volume:	9
Date:	2019
Publisher:	NATURE PUBLISHING GROUP
Place of Publication:	LONDON
ISSN:	2045-2322
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language SIRT1; TRANSDIFFERENTIATION; DIFFERENTIATION; ASSOCIATION; MUTATIONS; AUTOPHAGY; CALCIUM; INDUCE; CELLS; AMPK Multiple languages Multidisciplinary Sciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/13790