Rosiglitazone promotes development of a novel adipocyte population from bone marrow-derived circulating progenitor cells
Rosiglitazone promotes development of a novel adipocyte population from bone marrow-derived circulating progenitor cells
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DOI：
10.1172/jci28510
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发表时间：
2006-12-01
影响因子：
15.9
通讯作者：
Klemm, Dwight J.
中科院分区：
文献类型：
--
作者：
Crossno, Joseph T., Jr.;Majka, Susan M.;Klemm, Dwight J.
肥胖和体重增加的特征是脂肪组织质量增加，这是由于单个脂肪细胞大小的增加以及新脂肪细胞的产生。据信新的脂肪细胞来自于脂肪组织内的前脂肪细胞和间充质祖细胞。然而，来自其他组织（特别是骨髓）的祖细胞也有可能促进脂肪组织中新脂肪细胞的发育。我们通过将来自表达绿色荧光蛋白（GFP）的转基因小鼠的全骨髓细胞移植到野生型C57BL/6小鼠体内，并让它们接受高脂饮食或噻唑烷二酮（TZD）罗格列酮（ROSI）治疗数周来验证这一假设。对脂肪组织的组织学检查或对脂肪细胞的荧光激活细胞分选（FACS）显示存在绿色荧光蛋白阳性（GFP⁺）的多泡脂肪细胞（ML），其数量因罗格列酮治疗或高脂喂养而显著增加。这些多泡脂肪细胞表达脂联素、 perilipin、脂肪酸结合蛋白（FABP）、瘦素、C/EBPα和过氧化物酶体增殖物激活受体γ（PPARγ），但不表达解偶联蛋白 - 1（UCP - 1）、CD45造血谱系标记物或CD11b单核细胞标记物。它们还表现出线粒体含量增加。绿色荧光蛋白阳性（GFP⁺）多泡脂肪细胞的出现与罗格列酮治疗动物中循环中间充质和造血祖细胞水平的增加同时发生。我们得出结论，噻唑烷二酮类药物和高脂喂养促进骨髓来源的循环祖细胞向脂肪组织的迁移，并促进其分化为多泡脂肪细胞。
Obesity and weight gain are characterized by increased adipose tissue mass due to an increase in the size of individual adipocytes and the generation of new adipocytes. New adipocytes are believed to arise from resident adipose tissue preadipocytes and mesenchymal progenitor cells. However, it is possible that progenitor cells from other tissues, in particular BM, could also contribute to development of new adipocytes in adipose tissue. We tested this hypothesis by transplanting whole BM cells from GFP-expressing transgenic mice into wild-type C57BL/6 mice and subjecting them to a high-fat diet or treatment with the thiazolidinedione (TZD) rosiglitazone (ROSI) for several weeks. Histological examination of adipose tissue or FACS of adipocytes revealed the presence of GFP(+) multilocular (ML) adipocytes, whose number was significantly increased by ROSI treatment or high-fat feeding. These ML adipocytes expressed adiponectin, perilipin, fatty acid-binding protein (FABP), leptin, C/EBP alpha, and PPAR gamma but not uncoupling protein-1 (UCP-1), the CD45 hematopoietic lineage marker, or the CDllb monocyte marker. They also exhibited increased mitochondrial content. Appearance of GFP(+) ML adipocytes was contemporaneous with an increase in circulating levels of mesenchymal and hematopoietic progenitor cells in ROSI-treated animals. We conclude that TZDs and high-fat feeding promote the trafficking of BM-derived circulating progenitor cells to adipose tissue and their differentiation into ML adipocytes.