Chinese Academy of Medical Sciences, United States
Abstract: Adipocytes have the potential to dedifferentiate into multipotent mesenchymal cells. Recent studies demonstrated that elevated osmolarity could induce adipocyte dedifferentiation, representing an appealing procedure for the regenerative toolsets. However, it remains elusive about the molecular mechanism that underlies osmotic stress-induced reprogramming of adipocytes. Here we report that high osmolarity prompts the adipocytes to release mitochondrial component, which in turn enhances the secretion of TNF-a as a pro-inflammatory cytokine during the stress response. Importantly, TNF-a is essential for the activation of the Wnt/b- catenin signaling that drives adipocyte dedifferentiation. Despite the generation of multipotent cells, the osmotic stress-induced adipocyte dedifferentiation is accompanied by a significant level of apoptosis mediated by TNF-a. To circumvent this issue, we show that Wnt agonist 1, a small compound that directly activates the Wnt/b-catenin signaling could effectively induce the multipotent adipocyte dedifferentiation without promoting apoptosis. Our results defined the molecular mechanism of adipocytes reprograming in response to osmotic stress. Furthermore, we provide an efficient approach to induce adipocyte differentiation while mitigating apoptosis.
Funding Source: Shenzhen Science and Technology Innovation Commission; Shenzhen-Hong Kong Science and Technology Innovation Cooperation Zone Shenzhen Park Project;
