Biosynthetic regulation of monobutyrin, an adipocyte-secreted lipid with angiogenic activity

Wilkison, W.O.; Choy, L.; Spiegelman, B.M.

doi:10.1016/s0021-9258(18)55385-0

Cited by 29Lipid metabolism and biosynthesisAdipose Tissue and MetabolismPeroxisome Proliferator-Activated Receptors

Biosynthetic regulation of monobutyrin, an adipocyte-secreted lipid with angiogenic activity

Open access

Wilkison, W.O., Choy, L., Spiegelman, B.M.·1991·Journal of Biological Chemistry

DOI 10.1016/s0021-9258(18)55385-0

Open this paper in CoChat — free account

Abstract

1-Butyrylglycerol (monobutyrin) is a novel angiogenic compound that is synthesized and secreted during the differentiation of 3T3-F442A preadipocytes into adipocytes. To study the regulation of monobutyrin biosynthesis we have developed an assay utilizing the lgycerol kinase enzyme from Cellulomonas to quantitate the levels of this compound in cell-conditioned medium. Analysis of several cultured cell types, including tumor cell lines, indicated that monobutyrin production is detectable only from adipocytes, reaching a steady-state concentration of approximately 1.0 microM in conditioned medium. Monobutyrin synthesis was demonstrated in vitro using [14C]butyryl-CoA with total homogenate or particulate fractions from adipocytes. Similar fractions from non-adipocyte cell lines failed to synthesize monobutyrin. This biosynthetic activity was shown to be distinct by substrate competition studies from the microsomal sn-glycerol-3-phosphate acyltransferase, whose activity is known to increase during adipocyte differentiation. The production of monobutyrin was hormonally regulated, as the addition of epinephrine to adipocytes caused a 10-fold increase in the amount of monobutyrin secreted. These results indicate that monobutyrin synthesis is adipocyte specific, occurs through an apparently novel particulate enzyme system, and is regulated in a hormone-dependent manner. The implications of these results for adipose physiology and angiogenesis are discussed.

Integrity signals

Registry

Crossref · 10.1016/s0021-9258(18)55385-0

Cites

38 of 38 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Adipocytes can secrete pro-angiogenic lipid species such as monobutyrin.
“Moreover, adipocytes can secrete pro-angiogenic lipid species such as monobutyrin (41).”
From The ominous triad of adipose tissue dysfunction: inflammation, fibrosis, and impaired angiogenesis. (2017) · cites this paper as [41]

Vascular Endothelial Growth Factor Is a Secreted Angiogenic Mitogen
Leung, D. W., Cachianes, G., Kuang, W.-J., Goeddel, D. V., & Ferrara, N. (1989) · Science · doi:10.1126/science.2479986 · Cited by 4,988 · see citing works
Serial passaging and differentiation of myogenic cells isolated from dystrophic mouse muscle
Yaffe, D., & Saxel, O. (1977) · Nature · doi:10.1038/270725a0 · Cited by 2,153 · see citing works
Continuous growth and differentiation of human myeloid leukaemic cells in suspension culture
Collins, S. J., Gallo, R. C., & Gallagher, R. E. (1977) · Nature · doi:10.1038/270347a0 · Cited by 2,124 · see citing works
Minimization of variation in the response to different proteins of the Coomassie blue G dye-binding assay for protein
Read, S. M., & Northcote, D. H. (1981) · Analytical Biochemistry · doi:10.1016/0003-2697(81)90321-3 · Cited by 1,420 · see citing works
Macrophage-induced angiogenesis is mediated by tumour necrosis factor-α
Leibovich, S. J., Polverini, P. J., Shepard, H. M., Wiseman, D. M., Shively, V. P., & Nuseir, N. (1987) · Nature · doi:10.1038/329630a0 · Cited by 1,207 · see citing works
Establishment and characterization of a cloned line of C3H mouse embryo cells sensitive to postconfluence inhibition of division.
Reznikoff, C. A., Brankow, D. W., & Heidelberger, C. (1973) · PubMed · Cited by 1,125 · see citing works
Sublines of mouse 3T3 cells that accumulate lipid
Green, H., & Kehinde, O. (1974) · Cell · doi:10.1016/0092-8674(74)90126-3 · Cited by 928 · see citing works
Spontaneous heritable changes leading to increased adipose conversion in 3T3 cells
Green, H., & Kehinde, O. (1976) · Cell · doi:10.1016/0092-8674(76)90260-9 · Cited by 833 · see citing works
Enzymes of Glycerolipid Synthesis in Eukaryotes
Bell, R. M., & Coleman, R. (1980) · Annual Review of Biochemistry · doi:10.1146/annurev.bi.49.070180.002331 · Cited by 633 · see citing works
A Rapid and Simple Method for the Determination of Esterified Fatty Acids and for Total Fatty Acids in Blood
Stern, I., & Shapiro, B. (1953) · Journal of Clinical Pathology · doi:10.1136/jcp.6.2.158 · Cited by 569 · see citing works
Beta-cell lines derived from transgenic mice expressing a hybrid insulin gene-oncogene.
Efrat, S., Linde, S., Kofod, H., Spector, D. L., Delannoy, M., Grant, S. G. N., Hanahan, D., & Bækkeskov, S. (1988) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.85.23.9037 · Cited by 515 · see citing works
Purification and NH2-terminal amino acid sequence of guinea pig tumor-secreted vascular permeability factor.
Senger, D. R., Connolly, D. T., Water, L. V. D., Feder, J., & Dvorak, H. F. (1990) · PubMed · Cited by 500 · see citing works
Role of prostaglandin E1 and copper in angiogenesis.
Ziche, M., Jones, J. J., & Gullino, P. M. (1982) · PubMed · Cited by 394 · see citing works
Purification of a factor from human placenta that stimulates capillary endothelial cell protease production, DNA synthesis, and migration.
Moscatelli, D., Presta, M., & Rifkin, D. B. (1986) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.83.7.2091 · Cited by 353 · see citing works
PGE2 and Angiogenesis
Form, D. M., & Auerbach, R. (1983) · Experimental Biology and Medicine · doi:10.3181/00379727-172-41548 · Cited by 342 · see citing works
Biosynthesis of phosphatidyl glycerophosphate in Escherichia coli
Chang, Y.-Y., & Kennedy, E. P. (1967) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)38901-x · Cited by 222 · see citing works
A Survey of Transplantable and Transmissible Animal Tumors
Dunham, L. J., & Stewart, H. L. (1953) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/13.5.1299 · Cited by 193 · see citing works
A defined subgenomic fragment of in vitro synthesized Moloney sarcoma virus DNA can induce cell transformation upon transfection
Andersson, P., Goldfarb, M. P., & Weinberg, R. A. (1979) · Cell · doi:10.1016/0092-8674(79)90188-0 · Cited by 189 · see citing works
Increasing activity of enzymes on pathway of triacylglycerol synthesis during adipose conversion of 3T3 cells.
Kuri‐Harcuch, W., & Green, H. (1977) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)71879-6 · Cited by 151 · see citing works
Blood circulation in adipose tissue
Rosell, S., & Belfrage, E. (1979) · Physiological Reviews · doi:10.1152/physrev.1979.59.4.1078 · Cited by 151 · see citing works
1-Butyryl-Glycerol: A novel angiogenesis factor secreted by differentiating adipocytes
Dobson, D. E., Kambe, A. M., Block, E., Dion, T., Lu, H. Y., Castellot, J. J., & Spiegelman, B. M. (1990) · Cell · doi:10.1016/0092-8674(90)90803-m · Cited by 126 · see citing works
Differentiation-dependent stimulation of neovascularization and endothelial cell chemotaxis by 3T3 adipocytes.
Castellot, J. J., Karnovsky, M. J., & Spiegelman, B. M. (1982) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.79.18.5597 · Cited by 120 · see citing works
Radiometric assays for glycerol, glucose, and glycogen
Bradley, D. C., & Kaslow, H. R. (1989) · Analytical Biochemistry · doi:10.1016/0003-2697(89)90081-x · Cited by 119 · see citing works
Triacylglycerol synthesis in isolated fat cells. Evidence that the sn-glycerol-3-phosphate and dihydroxyacetone phosphate acyltransferase activities are dual catalytic functions of a single microsomal enzyme.
Schlossman, D. M., & Bell, R. M. (1976) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)33118-6 · Cited by 117 · see citing works
Physical properties of fatty acyl-CoA. Critical micelle concentrations and micellar size and shape.
Constantinides, P. P., & Steim, J. M. (1985) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)39646-1 · Cited by 111 · see citing works
Glycerol kinase: synthesis of dihydroxyacetone phosphate, sn-glycerol-3-phosphate, and chiral analogs
Crans, D. C., & Whitesides, G. M. (1985) · Journal of the American Chemical Society · doi:10.1021/ja00310a045 · Cited by 103 · see citing works
Induction of the Triglyceride Pathway Enzymes and of Lipolytic Enzymes during Differentiation in a 'Preadipocyte' Cell Line
Grimaldi, P. A., Négrel, R., & Ailhaud, G. P. (1978) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1978.tb12177.x · Cited by 93 · see citing works
L-myc cooperates with ras to transform primary rat embryo fibroblasts.
Birrer, M. J., Segal, S., DeGreve, J. S., Kaye, F. J., Sausville, E. A., & Minna, J. D. (1988) · Molecular and Cellular Biology · doi:10.1128/mcb.8.6.2668 · Cited by 91 · see citing works
Potent stimulation of vascular endothelial cell growth by differentiated 3T3 adipocytes.
Castellot, J. J., Karnovsky, M. J., & Spiegelman, B. M. (1980) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.77.10.6007 · Cited by 82 · see citing works
Glycerol kinase: substrate specificity
Crans, D. C., & Whitesides, G. M. (1985) · Journal of the American Chemical Society · doi:10.1021/ja00310a044 · Cited by 63 · see citing works
Selective changes in enzymes of the sn-glycerol 3-phosphate and dihydroxyacetone-phosphate pathways of triacylglycerol biosynthesis during differentiation of 3T3-L1 preadipocytes.
Coleman, R., & Bell, R. M. (1980) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)43883-0 · Cited by 61 · see citing works
Hemodynamic and metabolic correlates in adipose tissue: pathophysiologic considerations
Crandall, D. L., & DiGirolamo, M. (1990) · The FASEB Journal · doi:10.1096/fasebj.4.2.2404816 · Cited by 57 · see citing works
Effect of epinephrine and other lipolytic agents on intracellular lipolysis and lipoprotein lipase activity in 3T3-L1 adipocytes.
Chernick, S. S., Spooner, P. M., GARRISON, M. M., & Scow, R. O. (1987) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)38831-3 · Cited by 49 · see citing works
Blood Flow through Human Adipose Tissue during Lipolysis
Nielsen, S. L., Bitsch, V., Larsen, O. A., Lassen, N. A., & QUAADE, F. (1968) · Scandinavian Journal of Clinical and Laboratory Investigation · doi:10.3109/00365516809160956 · Cited by 43 · see citing works
Regulation of 3T3-L1 fibroblast differentiation by prostacyclin (prostaglandin I2)
Hopkins, N. K., & Gorman, R. R. (1981) · Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism · doi:10.1016/0005-2760(81)90174-0 · Cited by 41 · see citing works
Heparin potentiation of 3T3‐adipocyte stimulated angiogenesis: Mechanisms of action on endothelial cells
Castellot, J. J., Kambe, A. M., Dobson, D. E., & Spiegelman, B. M. (1986) · Journal of Cellular Physiology · doi:10.1002/jcp.1041270221 · Cited by 37 · see citing works
Cell-heritable stages of tumor progression in transgenic mice harboring the bovine papillomavirus type 1 genome.
Sippola-Thiele, M., Hanahan, D., & Howley, P. M. (1989) · Molecular and Cellular Biology · doi:10.1128/mcb.9.3.925 · Cited by 35 · see citing works
Stimulation and Inhibition of Lipolysis in Isolated Rat Adipocytes: Evidence for Age-Related Changes in Responses to Forskolin and PGE1
Hoffman, B. B., Chang, H., & Reaven, G. M. (1987) · Hormone and Metabolic Research · doi:10.1055/s-2007-1011823 · Cited by 7 · see citing works

Flagged first, then by citations

Sorted by citations

Minireview: The Adipocyte—At the Crossroads of Energy Homeostasis, Inflammation, and Atherosclerosis
Rajala, M. W., & Scherer, P. E. (2003) · Endocrinology · doi:10.1210/en.2003-0580 · Cited by 1,190 · see citing works
Angiogenesis modulates adipogenesis and obesity
Cao, Y. (2007) · Journal of Clinical Investigation · doi:10.1172/jci32239 · Cited by 736 · see citing works
The ominous triad of adipose tissue dysfunction: inflammation, fibrosis, and impaired angiogenesis.
Crewe, C., An, Y. A., & Scherer, P. E. (2017) · Journal of Clinical Investigation · doi:10.1172/jci88883 · Cited by 732 · see citing works
Implications of butyrate and its derivatives for gut health and animal production
Bedford, A., & Gong, J. (2017) · Animal nutrition · doi:10.1016/j.aninu.2017.08.010 · Cited by 459 · see citing works
Adipocyte Produces Matrix Metalloproteinases 2 and 9
Bouloumié, A., Sengenès, C., Portolan, G., Galitzky, J., & Lafontan, M. (2001) · Diabetes · doi:10.2337/diabetes.50.9.2080 · Cited by 329 · see citing works
The secretory function of adipocytes in the physiology of white adipose tissue
Wang, P., Mariman, E., Renes, J., & Keijer, J. (2008) · Journal of Cellular Physiology · doi:10.1002/jcp.21386 · Cited by 318 · see citing works
Adipose tissue: friend or foe?
Hassan, M. S., Latif, N., & Yacoub, M. H. (2012) · Nature Reviews Cardiology · doi:10.1038/nrcardio.2012.148 · Cited by 142 · see citing works
Molecular events in adipocyte development
Butterwith, S. C. (1994) · Pharmacology & Therapeutics · doi:10.1016/0163-7258(94)90018-3 · Cited by 66 · see citing works
Regulators of adipocyte precursor cells
Butterwith, S. C. (1997) · Poultry Science · doi:10.1093/ps/76.1.118 · Cited by 38 · see citing works
Adipose Tissue Dysfunction: A Multistep Process
Sun, K., & Scherer, P. E. (2010) · Research and Perspectives in Endocrine Interactions · doi:10.1007/978-3-642-13517-0_6 · Cited by 23 · see citing works
Biosynthesis of the vasoactive lipid monobutyrin. Central role of diacylglycerol.
Wilkison, W. O., & Spiegelman, B. M. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)53850-3 · Cited by 21 · see citing works
Characterization of glycerol uptake and glycerol kinase activity in rat hepatocytes cultured under different hormonal conditions
Westergaard, N., Madsen, P., & Lundgren, K. (1998) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/s0167-4889(98)00016-0 · Cited by 21 · see citing works
Adipocyte-endothelial cell interplay in adipose tissue physiology
Chaurasiya, V., Haridas, P. A. N., & Olkkonen, V. M. (2024) · Biochemical Pharmacology · doi:10.1016/j.bcp.2024.116081 · Cited by 19 · see citing works
Augmentation of Tendon Healing With Butyric Acid–Impregnated Sutures
Leek, B. T., Tasto, J. P., Tibor, L. M., Healey, R., Freemont, A. J., Linn, M. S., Chase, D. E., & Amiel, D. (2012) · The American Journal of Sports Medicine · doi:10.1177/0363546512450691 · Cited by 18 · see citing works
Vasodilation of rat retinal microvessels induced by monobutyrin. Dysregulation in diabetes.
Halvorsen, Y.-D., Bursell, S., Wilkison, W. O., Clermont, A. C., Brittis, M., McGovern, T. J., & Spiegelman, B. M. (1993) · Journal of Clinical Investigation · doi:10.1172/jci116908 · Cited by 17 · see citing works
Metabolism of fenbufen by cultured 3T3-L1 adipocytes: synthesis and metabolism of xenobiotic glycerolipids.
Dodds, P. F., Chou, S. C., Ranasinghe, A., & Coleman, R. (1995) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)41086-7 · Cited by 13 · see citing works
Depot‐Specific Biology of Adipose Tissues: Links to Fat Distribution and Metabolic Risk
Lee, M., & Fried, S. K. (2010) · doi:10.1002/9783527629527.ch15 · Cited by 12 · see citing works
Relationship between Cardiometabolic index and endometriosis in a US nationally representative sample: results from NHANES 1999-2006
Hou, J., Chen, W., Wang, R., Huang, X., Cao, X., & Wang, X. (2024) · Frontiers in Endocrinology · doi:10.3389/fendo.2024.1450965 · Cited by 10 · see citing works
The Role of Angiogenesis in Obesity
Yoon, M. (2014) · Journal of Life Science · doi:10.5352/jls.2014.24.5.573 · Cited by 7 · see citing works
Tensions Rise and Blood Flows Over Dysfunctional Fat
Corvera, S., & Czech, M. (2011) · Circulation · doi:10.1161/circulationaha.111.037804 · Cited by 6 · see citing works
De novo adipogenesis for reconstructive surgery
Kitagawa, Y., & Kawaguchi, N. (1999) · Cytotechnology · doi:10.1023/a:1008055702129 · Cited by 5 · see citing works
Pathophysiology of metalloproteinase matrix in relation to morbid obesity and associated pathologies
Mirică, R., Ionescu, M., Mirică, A., Ginghină, O., IOSIFESCU, R., Văcărașu, A., Ciotirlă, D., Roşca, A. E., Zăgrean, L., & Iordache, N. (2022) · The European Research Journal · doi:10.18621/eurj.1081324 · Cited by 3 · see citing works
Investigation of Vascular Endothelial Growth Factor and Endostatin Levels in Some Rat Tissues in Response to Cold Stress and Diet
Coban, F., & Yürekli, M. (2024) · Medical Science and Discovery · doi:10.36472/msd.v11i3.1117 · Cited by 1 · see citing works
Therapeutic potential of antiangiogenic agents for prevention and treatment of obesity
Cao, Y., Cao, R., & Xue, Y. (2008) · Future Lipidology · doi:10.2217/17460875.3.2.153 · Cited by 1 · see citing works
Proteomic, transcriptomic and epidemiological analysis of adipocyte-secreted proteins'towards a system biological understanding of adipocytes
Wang, P. (2007) · doi:10.26481/dis.20070329pw
Genetic Association of the Tenomodulin Gene (TNMD) with
Tolppanen, A. (2009)
Involvement in Adipose Differentiation
Bouloumié, A., Portolan, G., Galitzky, J., & Lafontan, M. (2001)
Adipose Tissue Biology: An Update Review
Meiliana, A., & Wijaya, A. (2009) · The Indonesian Biomedical Journal · doi:10.18585/inabj.v1i3.98
Monobutyrin
Salajegheh, A. (2016) · Springer eBooks · doi:10.1007/978-3-319-28140-7_32

Biosynthesis of the vasoactive lipid monobutyrin. Central role of diacylglycerol.
Wilkison, W. O., & Spiegelman, B. M. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)53850-3 · Cited by 21 · see citing works
1-Butyryl-Glycerol: A novel angiogenesis factor secreted by differentiating adipocytes
Dobson, D. E., Kambe, A. M., Block, E., Dion, T., Lu, H. Y., Castellot, J. J., & Spiegelman, B. M. (1990) · Cell · doi:10.1016/0092-8674(90)90803-m · Cited by 126 · see citing works
Cellular and Molecular Aspects of Adipose Tissue Development
Ailhaud, G. P., Grimaldi, P., & Négrel, R. (1992) · Annual Review of Nutrition · doi:10.1146/annurev.nu.12.070192.001231 · Cited by 679 · see citing works
Boiogito Increases the Synthesis and Secretion of Adiponectin by Promoting Differentiation in Cultured Human Adipocytes
古, 源., & コ, ゲ. (2023)
Links between De Novo Fatty Acid Synthesis and Leptin Secretion in Bovine Adipocytes
Kadokawa, H., Aikawa, K., Kimura, K., Blache, D., WILLIAMS, I. H., & Martin, G. B. (2007) · Journal of Veterinary Medical Science · doi:10.1292/jvms.69.225 · Cited by 4 · see citing works

Authors: Wilkison, W. O., Choy, L., & Spiegelman, B. M.
Affiliations: Dana-Farber Cancer Institute (US)
ORCID: Choy, L.
Spiegelman, B.M.
Venue: Journal of Biological Chemistry
Publisher: Elsevier BV
Published: 1991-09
Volume: 266
Issue: 25
Pages: 16886-16891
ISSN: 0021-9258 (ISSN-L)
DOI: 10.1016/s0021-9258(18)55385-0
OpenAlex: W1585894269
Cited by: 29
References: 38
Citations by year: 2024: 3 · 2022: 1 · 2017: 2 · 2016: 1 · 2014: 1 · 2012: 2
FWCI: 0.67
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
creativecommons.org/licenses/by/4.0/ (vor, 10636 d)
Locations: Journal of Biological Chemistry (publishedVersion, cc-by)
PubMed (publishedVersion)
Funders: National Institutes of Health (5r01dk042420-09, 5f32dk008277-03)
National Institute of Diabetes and Digestive and Kidney Diseases (DK08277, DK42420)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
Keywords: adipogenesis, angiogenesis, glycerol kinase, Cellulomonas, sn-glycerol-3-phosphate acyltransferase, adipose tissue physiology, 3T3-F442A preadipocytes
MeSH terms: Adipose Tissue, Alprostadil, Animals, Cell Differentiation, Cell Line, Epinephrine, Glycerides, Glycerol Kinase, Kinetics, Organ Specificity, Phosphorylation, Angiogenesis Inducing Agents, Mice

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Biosynthetic regulation of monobutyrin, an adipocyte-secreted lipid with angiogenic activity

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Cites

Cited by

Related

Record

About these checks