Dataset Information

Calcyphosine-like (CAPSL) is regulated in Multiple Symmetric Lipomatosis and is involved in Adipogenesis.

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.

SUBMITTER: Lindner A

PROVIDER: S-EPMC6559987 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Calcyphosine-like (CAPSL) is regulated in Multiple Symmetric Lipomatosis and is involved in Adipogenesis.

Lindner Angie A Marbach Felix F Tschernitz Sebastian S Ortner Christine C Berneburg Mark M Felthaus Oliver O Prantl Lukas L Kye Min Jeong MJ Rappl Gunter G Altmüller Janine J Thiele Holger H Schreml Stephan S Schreml Julia J

Scientific reports 20190611 1

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 CAP ...[more]

PMID: 31186450

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Project description:Multiple symmetric lipomatosis (MSL) is a rare disorder characterized by aberrant multiple and symmetric subcutaneous adipose tissue accumulation in the face, neck, shoulders, back, chest and abdomen, severely affecting the quality of life of patients. At present, precise MSL etiology and pathogenesis remain to be elucidated. The present study first utilized a digital gene expression technique with a next?generation sequencing platform to profile differentially expressed genes in three cases of MSL vs. normal control tissue. cDNA libraries from these tissue specimens were constructed and DNA sequenced for identification of differentially expressed genes, which underwent bioinformatic analysis using the Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) and protein?protein interaction (PPI) network analyses. As a result, a total of 859 differentially expressed genes were identified, including 308 upregulated genes (C19orf80, Apelin, C21orf33, FAM166B and HSD11B2 were mostly upregulated 6.984?, 4.670?, 4.412?, 3.693? and 3.561?fold, respectively) and 551 downregulated genes [FosB proto?oncogene, AP?1 transcription factor subunit (FOSB), selectin (SEL) E, RAR related orphan receptor (ROR) B, salt inducible kinase (SIK)1 and epidermal growth factor?like protein (EGFL)6 were mostly downregulated ?9.845, ?8.243, ?8.123, ?7.702 and ?7.664 fold, respectively). The GO functional enrichment analysis demonstrated these differentially expressed genes were predominantly involved in biological processes and cellular components, while the KEGG pathway enrichment analysis demonstrated that ribosome, non?alcoholic fatty liver disease, human T?lymphotropic virus type 1 (HTLV?I) infection and Alzheimer's disease pathways were altered in MSL. The PPI network data demonstrated ubiquitin C (UBC), translocator protein (TSPO), Jun Proto?Oncogene, AP?1 Transcription Factor (JUN) and FOS were among these differentially expressed genes that participated in regulation of adipocyte differentiation, although no previous study has linked them to MSL. In conclusion, the present study profiled differentially expressed genes in MSL and identified gene pathways that may be associated with MSL development and progression.

Dataset Information

Calcyphosine-like (CAPSL) is regulated in Multiple Symmetric Lipomatosis and is involved in Adipogenesis.

Publications

Calcyphosine-like (CAPSL) is regulated in Multiple Symmetric Lipomatosis and is involved in Adipogenesis.

Similar Datasets

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