1-Butyryl-Glycerol: A novel angiogenesis factor secreted by differentiating adipocytes

Deborah E. Dobson; Arbetta Kambe; Eric Block; Teresa Dion; Henry Lu; John J. Castellot; Bruce M. Spiegelman

doi:10.1016/0092-8674(90)90803-M

1-Butyryl-Glycerol: A novel angiogenesis factor secreted by differentiating adipocytes

Deborah E. Dobson, Arbetta Kambe, Eric Block, Teresa Dion, Henry Lu, John J. Castellot, Bruce M. Spiegelman

Department of Molecular Microbiology

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118 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	223-230
Number of pages	8
Journal	Cell
Volume	61
Issue number	2
DOIs	https://doi.org/10.1016/0092-8674(90)90803-M
State	Published - Apr 20 1990

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title = "1-Butyryl-Glycerol: A novel angiogenesis factor secreted by differentiating adipocytes",

abstract = "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.",

author = "Dobson, {Deborah E.} and Arbetta Kambe and Eric Block and Teresa Dion and Henry Lu and Castellot, {John J.} and Spiegelman, {Bruce M.}",

note = "Funding Information: We gratefully acknowledge Robert Chaplinsky, Benjaman Caleb, and Kimberly Zinnack for their expert technical assistance and Stephen Beverley, Klaus Biemann, Catherine Costello, John Fiddes, Morris Kar-novsky, Mark Snyder, and William Wilkison for helpful discussions. This work was supported by National Institutes of Health grants HL30290, DK42420, and DK31405. D. E. D. was a Fellow of the Charles King Trust. J. J. C. and 6. M. S. are Established Investigators of the American Heart Association. Mass spectral analyses were performed at the MIT MS facility, which is supported by National Institutes of Health grant RR00317 to K. Biemann.",

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AU - Dobson, Deborah E.

AU - Kambe, Arbetta

AU - Block, Eric

AU - Dion, Teresa

AU - Lu, Henry

AU - Castellot, John J.

AU - Spiegelman, Bruce M.

N1 - Funding Information: We gratefully acknowledge Robert Chaplinsky, Benjaman Caleb, and Kimberly Zinnack for their expert technical assistance and Stephen Beverley, Klaus Biemann, Catherine Costello, John Fiddes, Morris Kar-novsky, Mark Snyder, and William Wilkison for helpful discussions. This work was supported by National Institutes of Health grants HL30290, DK42420, and DK31405. D. E. D. was a Fellow of the Charles King Trust. J. J. C. and 6. M. S. are Established Investigators of the American Heart Association. Mass spectral analyses were performed at the MIT MS facility, which is supported by National Institutes of Health grant RR00317 to K. Biemann.

PY - 1990/4/20

Y1 - 1990/4/20

N2 - 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.

AB - 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.

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1-Butyryl-Glycerol: A novel angiogenesis factor secreted by differentiating adipocytes

Abstract

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