Altered Metabolism and Lipodystrophy in the Early B-Cell Factor 1-Deficient Mouse
Altered Metabolism and Lipodystrophy in the Early B-Cell Factor 1-Deficient Mouse
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DOI：
10.1210/en.2009-0987
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发表时间：
2010-04-01
期刊：
影响因子：
4.8
通讯作者：
Horowitz, Mark C.
中科院分区：
文献类型：
--
作者：
Fretz, Jackie A.;Nelson, Tracy;Horowitz, Mark C.
我们以前报道过，转录因子早期B细胞因子（Ebf 1）缺陷的小鼠表现出显着增加的成骨细胞，骨形成率，血清骨钙素的数量，但Ebf 1（-/-）小鼠的骨髓也显着增加骨髓肥胖。本研究的目的是分析Ebf 1（-/-）小鼠骨形态改变的代谢表型。尽管骨髓脂肪增多，但身体其他部位的白色脂肪组织沉积严重减少（皮下40- 50%，腹部80-85%）。棕色脂肪显示脂质沉积减少。与野生型相比，皮下和性腺周围白色脂肪组织显示Ebf 1（-/-）组织中过氧化物酶体增殖物激活受体-γ 2和CCAAT/增强子结合蛋白-β的mRNA转录物减少。与同窝对照组相比，Ebf 1（-/-）动物的循环瘦素水平降低（下降65-95%），而脂联素在2周龄后保持相当。血清分析还发现Ebf 1（-/-）动物低血糖和低血糖。在ip注射胰岛素后，Ebf 1（-/-）小鼠的血清葡萄糖水平需要更长时间才能恢复，并且在葡萄糖激发后，Ebf 1（-/-）小鼠的血清葡萄糖水平几乎达到野生型小鼠的两倍。循环胰腺激素的测量显示Ebf 1（-/-）小鼠的胰岛素水平正常或降低，而胰高血糖素显著增加（增加1.7至8.5倍）。在代谢方面，Ebf 1（-/-）小鼠的O-2消耗量、CO2产生量、食物和水摄入量以及活动量增加。然而，与对照组相比，Ebf 1（-/-）小鼠的胚胎发生标记物减少。总之，Ebf 1（-/-）缺陷动物表现出脂肪组织沉积缺陷，骨髓肥胖增加，葡萄糖动员受损。（内分泌学151：1611-1621，2010）
We previously reported that mice deficient for the transcription factor early B-cell factor (Ebf1) exhibit markedly increased numbers of osteoblasts, bone formation rate, and serum osteocalcin, but the bone marrow of Ebf1(-/-) mice is also striking in its increased marrow adiposity. The purpose of this work was to analyze the metabolic phenotype that accompanies the altered bone morphology of Ebf1(-/-) mice. Whereas marrow adiposity was increased, deposition of white adipose tissue in other regions of the body was severely reduced (sc 40-50%, abdominally 80-85%). Brown adipose exhibited decreased lipid deposition. Subcutaneous and perigonadal white adipose tissue showed a decrease in mRNA transcripts for peroxisomal proliferator-activated receptor-gamma 2 and CCAAT/enhancer-binding protein-beta in Ebf1(-/-) tissue compared with wild type. Circulating levels of leptin were decreased in Ebf1(-/-) animals compared with their littermate controls (down 65-95%), whereas adiponectin remained comparable after 2 wk of age. Serum analysis also found the Ebf1(-/-) animals were hypoglycemic and hypotriglyceridemic. After ip injection of insulin, the serum glucose levels in Ebf1(-/-) mice took longer to recover, and after a glucose challenge the Ebf1(-/-) animals reached serum glucose levels almost twice that of their wild-type counterparts. Measurement of circulating pancreatic hormones revealed normal or reduced insulin levels in the Ebf1(-/-) mice, whereas glucagon was significantly increased (up 1.7-to 8.5-fold). Metabolically the Ebf1(-/-) mice had increased O-2 consumption, CO2 production, food and water intake, and activity. Markers for gluconeogenesis, however, were decreased in the Ebf1(-/-) mice compared with controls. In conclusion, the Ebf1(-/-) deficient animals exhibit defects in adipose tissue deposition with increased marrow adiposity and impaired glucose mobilization. (Endocrinology 151: 1611-1621, 2010)