Dobson D E, Kambe A, Block E, Dion T, Lu H, Castellot J J, Spiegelman B M
Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115.
Cell. 1990 Apr 20;61(2):223-30. doi: 10.1016/0092-8674(90)90803-m.
Differentiation of adipocytes is accompanied by secretion of molecules stimulating angiogenesis in vivo and endothelial cell growth and motility in vitro. We demonstrate that the angiogenic and motility-stimulating activities secreted by adipocytes are separable from the endothelial cell mitogenic activity by fractionation of adipocyte-conditioned medium. The major differentiation-dependent angiogenic molecule was purified and identified by GCMS as 1-butyryl-glycerol (monobutyrin). Monobutyrin levels increase at least 200-fold during adipocyte differentiation and represent a major fraction of the total angiogenic activity. Synthetic monobutyrin shows the same spectrum of biological activities as the adipocyte-derived factor: stimulation of angiogenesis in vivo and microvascular endothelial cell motility in vitro, with no effect on endothelial cell proliferation. Angiogenesis is stimulated at doses as low as 20 pg when tested in the chick chorioallantoic membrane assay. These results strongly suggest that monobutyrin is a key regulatory molecule in an angiogenic process linked to normal cellular and tissue development.
脂肪细胞的分化伴随着在体内刺激血管生成以及在体外刺激内皮细胞生长和迁移的分子的分泌。我们证明，通过对脂肪细胞条件培养基进行分级分离，脂肪细胞分泌的血管生成和迁移刺激活性与内皮细胞促有丝分裂活性是可分离的。通过气相色谱-质谱联用（GCMS）纯化并鉴定出主要的依赖分化的血管生成分子为1-丁酰甘油（单丁酸甘油酯）。在脂肪细胞分化过程中，单丁酸甘油酯水平至少增加200倍，并且占总血管生成活性的主要部分。合成的单丁酸甘油酯显示出与脂肪细胞衍生因子相同的生物活性谱：在体内刺激血管生成，在体外刺激微血管内皮细胞迁移，而对内皮细胞增殖没有影响。在鸡胚绒毛尿囊膜试验中测试时，低至20皮克的剂量就能刺激血管生成。这些结果强烈表明，单丁酸甘油酯是与正常细胞和组织发育相关的血管生成过程中的关键调节分子。
