研究実績の概要 |
First, I have successfully create of genetically engineered CD206+ M2 like-macrophage-specific Nampt knock-out (KO) transgenic mice. I found that tamoxifen (TAM) administration did not affect the body weight of the chow-fed mice. After the administration of TAM I have performed ipGTT (intraperitoneal glucose tolerance test) and ITT (insulin tolerance test). My data showed that there is no significant difference between CD206 specific Nampt-KO mice and control mice normal chow-fed conditions. Then these mice were put on high fat diet (HFD). In consistent with my hypothesis, Nampt-KO mice gaining more body weight compared to the control mice. This data strongly suggested that CD206+ macrophages regulated diet-induced obesity or weight gain via Nampt-derived NAD+, with worsen glucose metabolism. My data suggest that CD206 gene have worsen effect on adipose tissue metabolism in obese states, which further worsen by Nampt KO. However, underlying molecular mechanism is unknown. My data also showed that CD206-positive macrophages shows inflammatory gene markers (Il1b, Tnfa, CD11c) after 12 weeks of HFD-feeding. Next, I am going to work on CD206-/-(CD206 gene knock-out) mice to evaluate how CD206 M2 macrophages is involved in regulation adipose tissue metabolism in obese conditions. I will perform GTT and ITT of these obese mice, and will harvest the tissue after sacrifice the mice. I will perform immunohistochemistry, RNA extraction, western blotting, flow cytometry, the qPCR of FACS sorted CD206+ macrophages to elucidate the underlying mechanism.
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今後の研究の推進方策 |
Currently, I have been working on CD206+ M2 macrophage-specific Nampt knock-out (KO) transgenic mice. I found that tamoxifen (TAM) administration did not affect the body weight of the chow-fed mice. After the administration of TAM I have performed GTT and ITT. In consistent with my hypothesis, Nampt-KO mice gaining more body weight compared to the control mice. My data showed that there is significant difference between CD206 specific Nampt-KO mice and control mice normal high fat diet (HFD) conditions. My data also showed that CD206-positive macrophages shows inflammatory gene markers (Il1b, Tnfa, CD11c) after 12 weeks of HFD-feeding. Next, I am going to work on CD206-/-(CD206 gene knock-out) mice to evaluate how CD206 M2 macrophages is involved in regulation adipose tissue metabolism in obese conditions. I will perform GTT and ITT of these obese mice, and will harvest the tissue after sacrifice the mice. I will perform immunohistochemistry, RNA extraction, western blotting, flow cytometry, the qPCR of FACS sorted CD206+ macrophages to elucidate the underlying mechanism.
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