Loss of menin mediated by endothelial cells treated with CoPP is associated with increased maturation of adipocytes

Abstract

Oxidative stress is caused by an increase in reactive oxygen species (ROS) relative to the antioxidant defense system. An increase in ROS is known to decrease vascular function, increase inflammatory cytokines, and promote adipocyte hypertrophy. A known regulator of the oxidative stress response is the heat shock protein, heme-oxygenase 1 (HO-1), which is induced by cobalt protoporphyrin IX (CoPP). Menin was recently found to promote the sustained expression of heat shock proteins and is implicated in the regulation of oxidative stress. In this study, we investigated how changes in menin expression affected adipogenesis via the interaction between endothelial cells and adipocytes in response to CoPP treatment during oxidative stress. Using angiotensin II (Ang II) to induce oxidative stress in endothelial cells and adipocytes, we observed the induction of various cytokines including EGF, VEGF, angiogenin, IL-6, and MCP-1. Preadipocytes cultured in endothelial cell conditioned media treated with Ang II showed no changes in differentiation markers. Preadipocytes treated with the endothelial cell-conditioned media pretreated with CoPP resulted in an increase in the number of adipocytes, which expressed higher levels of adipocyte differentiation markers in direct correlation with the complete downregulation of the stress response regulator, menin. This change was not detected in adipocytes directly treated with CoPP alone. Therefore, we concluded that loss of menin is associated with the maturation of adipocytes induced by conditioned media from endothelial cells treated with CoPP.

Type 2 diabetes model TSOD mouse is exposed to oxidative stress at young age

“…( 13 , 15 ) ROS, in turn, are thought to induce adipocyte hypertrophy, which contributes to the progression of obesity. ( 17 ) Numerous reports have suggested that oxidative stress and obesity are exacerbated when those two factors interact with each other. ( 18 , 19 ) Although further studies are required to elucidate the mechanism underlying the induction of oxidative stress in TSOD mice, our findings suggest that oxidative stress in young TSOD mice is attributed to ROS production associated with obesity.…”

Loss of the tumour suppressor gene AIP mediates the browning of human brown fat tumours

“…For instance, patients affected by the MEN1 syndrome have been reported to show benign white fat tumours (lipomas) with loss of the wild‐type MEN1 allele , and it has been suggested that lipomas are overrepresented in this syndrome as compared with the general population . Furthermore, it has been shown that downregulation of the protein product of MEN1 – menin – is associated with the induction of PPARG and an increase in the number of mature adipocytes . Peroxisome proliferator‐activated receptor‐γ (PPARG) is a major regulator of adipogenesis; it is both necessary and sufficient for this process, as it is able to transdifferentiate fibroblasts and myoblasts into adipocytes .…”