研究実績の概要 |
The goal of this project is to identify the role of Group 2 innate lymphoid cells (ILC2) in the early stages of expansion of white adipose tissue that occurs during obesity. In vivo, early activation of adipocyte precursors (APs) and accumulation of fat mass was blunted in Rag2-Il2rg knockout mice that lack all innate lymphoid cells, compared to Rag2 knockout mice, which lack adaptive immune cells but have ILC2. These data suggest that ILC2 play an important role in AP activation and obesity-induced remodeling of adipocytes. We used RNA-sequence analysis to analyze differences in AP gene expression at steady state and 3-days post-HFD in Rag2-Il2rg knockout mice compared to Rag2 knockout. This project is currently ongoing as we seek to identify the key genes and pathways that differ between these two mice and how this affects the ability of the APs to undergo activation and differentiation to adipocytes. Using an in vitro indirect co-culture system to assess effects of ILC2 on adipocyte differentiation, we found that soluble factors from ILC2s inhibited lipid accumulation in adipocyte precursors during differentiation and increased appearance of fibroblastic adipocytes with increased production of collagens and extracellular matrix proteins. Using next-generation proteomics analysis, we identified several proteins involved in lipogenesis that were down-regulated and up regulation of proteins involved in extracellular matrix remodelling. Overall, our findings to date show that ILC2 induce proliferation and activation of APs and promote ECM remodeling.
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