| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Research Abstract |
Metabolic syndrome is a major risk factor for cardiovascular and metabolic diseases, and playing a central role in the development of metabolic syndrome and its clinical consequences is visceral obesity. Recent studies have shown that obesity induces chronic local inflammation in adipose tissue, and that the complex interplay between adipocytes and immune cells are important for the development of adipose tissue inflammation and systemic metabolic abnormalities. However, it is still unclear how inflammatory processes are initiated in obese adipose tissue. Here, we report that a novel cell population derived from adipocyte progenitor cells triggers the early inflammatory processes in adipose tissue. We identified RAD51, a DNA repair and recombination factor, as essential for the cell cycle progression that is coupled with adipocyte differentiation. Analysis of Rad51^<+/-> mice and in vitro experiments demonstrated that Rad51 is required for adipocyte hyperplasia induced by high-fat diet(HFD). Interestingly, Rad51^<+/-> mice were protected from inflammation in obese visceral adipose tissue, suggesting that adipocyte hyperplasia and adipose inflammation may be linked. We found that during obesity in WT mice, Lin^+CD34^+Sca1^<mid> CD24^+cells were generated from adipocyte progenitor cells and triggered accumulation of monocytes/macrophages and inflammation in adipose tissue partly via the production of proinflammatory cytokines. Meanwhile, because development of Lin^+CD34^+Sca1^<mid> CD24^+cells by diet-induced obesity was suppressed in Rad51^<+/-> mice, adipose tissue inflammation was subsequently not initiated. Our results clearly demonstrate that Lin^+CD34^+Sca1^<mid> CD24^+cells are the link between obesity and initiation of inflammation in adipose tissue.
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