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.

A case report of Madelung's disease in China

“…The distribution and types of adipocytes in Madelung's disease are similar to brown adipose tissue (BAT) [12] . The diseased tissue of Madelung's disease is not hypertrophy of existing adipose cells, but proliferation of adipose cells, which is involved in the formation of Madelung's disease.In lipomatous tissue, Sanna M [13] evidenced AKT, CK2, and ERK1/2 hyperactivation. Most literatures reported that the main cause of Madelung's disease is chronic alcoholism caused by long-term heavy alcohol consumption, which leads to mitochondrial cell dysfunction, premature oxidation of mitochondrial DNA or mitochondrial DNA mutation.…”

Adipogenic progenitors in different organs: Pathophysiological implications

“…Adult stem cell senescence has emerged as an attractive theory for the decline in mammalian tissue and organ dysfunction of a variety of cardiovascular and metabolic diseases [133][134][135][136]. In this view, a better characterization of human AT progenitors and the precise definition of their recruitment and regulation could improve the possibility of targeting specific pathways acting in the AT expansion [28,137,138]. A further fascinating mechanism explaining the origin and growth of ectopic AT could be the colonization by ASCs of other organs, such as muscle or bone marrow.…”