1-Butyryl-glycerol: a novel angiogenesis factor secreted by differentiating adipocytes.
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.
Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115.
D E
DE
Dobson
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A
Kambe
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E
Block
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Dion
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Lu
J J
JJ
Castellot
B M
BM
Spiegelman
D000273:Adipose Tissue / Q000166:cytology* / Q000378:metabolism; D043925:Angiogenesis Inducing Agents; D000818:Animals; D001681:Biological Assay; D002454:Cell Differentiation; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D002642:Chick Embryo; D002855:Chromatography, Thin Layer; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D008401:Gas Chromatography-Mass Spectrometry; D005989:Glycerides / Q000096:biosynthesis* / Q000302:isolation & purification / Q000494:pharmacology; D006133:Growth Substances; D008297:Male; D009389:Neovascularization, Pathologic; D051381:Rats
D043925:Angiogenesis Inducing Agents; D005989:Glycerides; D006133:Growth Substances; C063895:1-butyrylglycerol