Thermogenic beige fat improves metabolism and prevents obesity.Emerging evidence shows that the activation of M2 macrophages stimulates beige adipogenesis,whereas the activation of Ml macrophages,which play a major ro...Thermogenic beige fat improves metabolism and prevents obesity.Emerging evidence shows that the activation of M2 macrophages stimulates beige adipogenesis,whereas the activation of Ml macrophages,which play a major role in inflammation,impedes beige adipogenesis.Thus,the identification of factors that regulate adipose tissue macrophages(ATMs)will help clarify the mechanism involved in beiging.Here,we found that one of the secreted proteins in adipose tissue,namely,BMP4,alters the ATM profile in subcutaneous adipose tissue by activating M2 and inhibiting Ml macrophages.Mechanistically,the BMP4-stimutated p38/MAPK/STAT6/PI3K-AKT signalling pathway is involved.Meanwhile,BMP4 improved the potency of M2 macrophages to induce beige fat biogenesis.Considering that the overexpression of BMP4 in adipose tissue promotes the beiging of subcutaneous adipose tissue and improves insulin sensitivity,these findings provide evidence that BMP4 acts as an activator of beige fat by targeting immuno-metabolic pathways.展开更多
目的:建立骨形态发生蛋白4(bone morphogenetic protein 4,BMP4)、脱钙骨基质和切断跟腱诱导的异位骨化动物模型,并初步探讨其形成机制,为异位骨化的研究奠定实验基础。方法:制备动物模型:(1)构建BMP4重组腺病毒,实验组裸鼠的一侧腓肠...目的:建立骨形态发生蛋白4(bone morphogenetic protein 4,BMP4)、脱钙骨基质和切断跟腱诱导的异位骨化动物模型,并初步探讨其形成机制,为异位骨化的研究奠定实验基础。方法:制备动物模型:(1)构建BMP4重组腺病毒,实验组裸鼠的一侧腓肠肌内注入50μl1×107pfu BMP4重组腺病毒液,对照组腓肠肌内注入50μl1×107pfu空病毒液。4周后行X线和组织学检查。(2)无菌条件下,股后外侧入路,将50mg脱钙骨基质植入裸鼠股后肌群内,4周后行X线和组织学检查。(3)20只小鼠于跟腱中点行跟腱切断术,10周后行X线和组织学检查。结果:X线和组织学检查显示4周后,注射BMP4重组腺病毒的动物均出现异位骨,注射空病毒组未见异位骨形成。4周后,植入脱钙骨基质的动物均出现异位骨。10周后,行跟腱切断术的动物均在跟腱部位出现异位骨。结论:BMP4、脱钙骨基质和切断跟腱可有效诱导异位骨化,结果稳定可靠。展开更多
基金grants from the National Natural Science Foundation of China(NSFC81390353 to Q.-Q.T.,31571471 to Q.-Q.T.,and 31670787 to S.-W.Q.)+1 种基金the Ministry of Science and Technology of China(MOST2013CB530601 to Q.-Q.T.).
文摘Thermogenic beige fat improves metabolism and prevents obesity.Emerging evidence shows that the activation of M2 macrophages stimulates beige adipogenesis,whereas the activation of Ml macrophages,which play a major role in inflammation,impedes beige adipogenesis.Thus,the identification of factors that regulate adipose tissue macrophages(ATMs)will help clarify the mechanism involved in beiging.Here,we found that one of the secreted proteins in adipose tissue,namely,BMP4,alters the ATM profile in subcutaneous adipose tissue by activating M2 and inhibiting Ml macrophages.Mechanistically,the BMP4-stimutated p38/MAPK/STAT6/PI3K-AKT signalling pathway is involved.Meanwhile,BMP4 improved the potency of M2 macrophages to induce beige fat biogenesis.Considering that the overexpression of BMP4 in adipose tissue promotes the beiging of subcutaneous adipose tissue and improves insulin sensitivity,these findings provide evidence that BMP4 acts as an activator of beige fat by targeting immuno-metabolic pathways.
文摘目的:建立骨形态发生蛋白4(bone morphogenetic protein 4,BMP4)、脱钙骨基质和切断跟腱诱导的异位骨化动物模型,并初步探讨其形成机制,为异位骨化的研究奠定实验基础。方法:制备动物模型:(1)构建BMP4重组腺病毒,实验组裸鼠的一侧腓肠肌内注入50μl1×107pfu BMP4重组腺病毒液,对照组腓肠肌内注入50μl1×107pfu空病毒液。4周后行X线和组织学检查。(2)无菌条件下,股后外侧入路,将50mg脱钙骨基质植入裸鼠股后肌群内,4周后行X线和组织学检查。(3)20只小鼠于跟腱中点行跟腱切断术,10周后行X线和组织学检查。结果:X线和组织学检查显示4周后,注射BMP4重组腺病毒的动物均出现异位骨,注射空病毒组未见异位骨形成。4周后,植入脱钙骨基质的动物均出现异位骨。10周后,行跟腱切断术的动物均在跟腱部位出现异位骨。结论:BMP4、脱钙骨基质和切断跟腱可有效诱导异位骨化,结果稳定可靠。
