Calcyphosine-like (CAPSL) is regulated in multiple symmetric lipomatosis and is involved in adipogenesis
Autor: | Christine Ortner, Lukas Prantl, Stephan Schreml, Sebastian Tschernitz, Janine Altmüller, Mark Berneburg, Holger Thiele, Gunter Rappl, Angie Lindner, Felix Marbach, Oliver Felthaus, Min Jeong Kye, Julia Schreml |
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Jazyk: | angličtina |
Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
Male Candidate gene endocrine system Adipose tissue lcsh:Medicine Biology Article GTP Phosphohydrolases Mitochondrial Proteins 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Downregulation and upregulation Sirtuin 1 Adipocyte Obligate carrier Exome Sequencing Autophagy DNA metabolism Adipocytes Animals Humans Genetic Predisposition to Disease Age of Onset lcsh:Science Gene Exome sequencing Genetics Multidisciplinary Adipogenesis lcsh:R fungi Cell Differentiation Pedigree 030104 developmental biology Mechanisms of disease chemistry Adipose Tissue Gene Expression Regulation Mutation Lipomatosis Multiple Symmetrical lcsh:Q Female Gene expression Technology Platforms 030217 neurology & neurosurgery |
Zdroj: | Scientific Reports Scientific Reports, Vol 9, Iss 1, Pp 1-11 (2019) |
Popis: | 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. |
Databáze: | OpenAIRE |
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