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 Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 49070:Immunology-related
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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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| Project Status |
Discontinued (Fiscal Year 2019)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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| Keywords | ILC2 / adipose tissue / adipocyte precursor / adipogenesis / obesity / immunometabolism / homeostasis |
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| Outline of Annual Research Achievements |
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.
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Report
(2 results)
Research Products
(2 results)
