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White Adipose Tissue Expansion in Multiple Symmetric Lipomatosis Is Associated with Upregulation of CK2, AKT and ERK1/2.

ABSTRACT: Multiple symmetric lipomatosis (MSL) is a rare disorder characterized by overgrowing lipomatous tissue (LT) in the subcutaneous adipose tissue (SAT). What LT is and how it expands are not completely understood; previous data suggested that it could derive from brown AT precursors. In six MSL type I patients, we compared LT morphology by histological and immunohistochemistry (IHC) analysis, gene expression, by qPCR, kinase activity, by Western Blot and in vitro assay to paired-control SAT using AT from patients with pheochromocytoma as a human browning reference. In the stromal vascular fraction (SVF), we quantified adipose stem cells (ASCs) by flow cytometry, the proliferation rate, white and beige adipogenic potential and clonogenicity and adipogenicity by a limiting dilution assay. LT displayed white AT morphology and expression pattern and did not show increased levels of the brown-specific marker UCP1. In LT, we evidenced AKT, CK2 and ERK1/2 hyperactivation. LT-SVF contained increased ASCs, proliferated faster, sprouted clones and differentiated into adipocytes better than the control, displaying enhanced white adipogenic potential but not increased browning compared to SAT. In conclusion, LT is a white AT depot expanding by hyperplasia through increased stemness and enhanced white adipogenesis upregulating AKT, CK2 and ERK1/2, which could represent new targets to counteract MSL.

SUBMITTER: Sanna M

PROVIDER: S-EPMC7662313 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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White Adipose Tissue Expansion in Multiple Symmetric Lipomatosis Is Associated with Upregulation of CK2, AKT and ERK1/2.

Sanna Marta M Borgo Christian C Compagnin Chiara C Favaretto Francesca F Vindigni Vincenzo V Trento Mariangela M Bettini Silvia S Comin Alessandra A Belligoli Anna A Rugge Massimo M Bassetto Franco F Donella-Deana Arianna A Vettor Roberto R Busetto Luca L Milan Gabriella G

International journal of molecular sciences 20201026 21

Multiple symmetric lipomatosis (MSL) is a rare disorder characterized by overgrowing lipomatous tissue (LT) in the subcutaneous adipose tissue (SAT). What LT is and how it expands are not completely understood; previous data suggested that it could derive from brown AT precursors. In six MSL type I patients, we compared LT morphology by histological and immunohistochemistry (IHC) analysis, gene expression, by qPCR, kinase activity, by Western Blot and in vitro assay to paired-control SAT using A ...[more]

PMID: 33114687

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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

White Adipose Tissue Expansion in Multiple Symmetric Lipomatosis Is Associated with Upregulation of CK2, AKT and ERK1/2.

Publications

White Adipose Tissue Expansion in Multiple Symmetric Lipomatosis Is Associated with Upregulation of CK2, AKT and ERK1/2.

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