2018 Fiscal Year Research-status Report
Role of group 2 innate lymphoid cells in regulation of adipocyte development and function in steady state and in obesity
| Project/Area Number |
18K15202
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| Research Institution | Institute of Physical and Chemical Research |
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Principal Investigator |
EALEY KAFI 国立研究開発法人理化学研究所, 生命医科学研究センター, リサーチアソシエイト (70715193)
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Keywords | ILC2 / obesity |
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| Outline of Annual Research Achievements |
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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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
This project is progressing smoothly because we have observed the phenomenon that ILC2 play a role in early activation of adipocyte precursors in obesity. The next stage is to identify the mechanisms for the phenomenon that we observed.
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| Strategy for Future Research Activity |
Future plans:
1. Single-cell RNA seq analysis of adipocyte precursors from ILC2-deficient mice vs wild type mice under steady state and high fat conditions to determine the ILC2-mediated activation pathways.
2. In vitro knockdown studies of identified genes to confirm mechanism of ILC2-induced activation.
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Research Products
(2 results)
