| 研究実績の概要 |
During obesity development, new mature adipocytes arise from the differentiation of adipocyte precursor (AP) cells within WAT and the extracellular matrix (ECM) of adipose tissues undergoes remodeling. Group 2 innate lymphoid cells (ILC2s) are most abundant in visceral WAT and have been reported to be important for maintaining adipose tissue homeostasis. We hypothesized that ILC2s may be important for regulating AP activation and differentiation in visceral adipose tissue.
We found that soluble factors from ILC2s inhibited lipid accumulation in APs during differentiation and increased appearance of adipocytes with a fibroblastic phenotype, with increased production of collagens and ECM proteins. Using next-generation proteomics analysis, we identified several proteins involved in lipogenesis that were downregulated and proteins involved in cell-cell adhesion and ECM stability and remodeling significantly upregulated by ILC2-derived factors. In vivo, early AP activation induced by HFD feeding, was associated with upregulation of pathways involved in ECM production. Early AP activation was significantly blunted in Il2rg-/-Rag2-/- mice that lack adaptive and innate lymphoid cells, compared to Rag2-/- mice that lack adaptive lymphoid cells but have innate lymphoid cells, including ILC2. These data suggest that activated adipose-tissue resident ILC2s may inhibit cellular bioenergetic pathways to prevent excessive lipid accumulation upon early exposure to a high fat diet and may also be involved in remodeling of the extracellular matrix to accommodate excess energy.
|
