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Angiogenesis modulates adipogenesis and obesity
Open accessAbstract
Substantial evidence shows that neoplastic and nonneoplastic tissue growth is dependent on angiogenesis. Neovascularization and adipogenesis are temporally and spatially coupled processes during prenatal life and they continue to reciprocally interact via paracrine signaling systems throughout adult life. Activated adipocytes produce multiple angiogenic factors including leptin, angiopoietins, HGF, GM-CSF, VEGF, FGF-2, and TGF-beta, which either alone or collectively stimulate neovascularization during fat mass expansion. Thus antiangiogenic agents provide a novel therapeutic option for prevention and treatment of human obesity and its related disorders.
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“The newly formed vascular network is crucial for adipogenesis and AT expansion (64,65).”
From Adipose tissue remodeling and obesity (2011) · cites this paper as [64]
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BackgroundThe spatiotemporal development of adipose tissue
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“…or macrophage depletion caused a definite impairment in the tissue architecture of EAT, which then resulted in interference in adipose tissue development, a finding consistent with previous reports (Rupnick et al., 2002; Brakenhielm et al., 2004; Lijnen et al., 2006; Cao, 2007; Cao, 2010).”
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“Maternal obesity may affect these anti-angiogenic factors via a number of adipokine-mediated pathways (165) but their crosstalk is poorly characterized in human pregnancies.”
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“Reduced blood supply could oppose adipogenesis because angiogenesis and adipogenesis are developmentally and functionally linked (Cao, 2007; Rupnick et al., 2002).”
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“Notably, increased free fatty acid levels may induce endothelial dysfunction and altered transendothelial transport (43,44), while leptin modulates angiogenesis under hypoxic conditions, having a direct effect on endothelium and VEGF expression (45,46).”
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“Adipose tissues and vasculature are the most plastic, growing, regressing, and remodeling throughout the life span (2).”
BackgroundInfluentialAdipose Tissue Fibrosis in Obesity: Etiology and Challenges
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BackgroundInfluentialPigment Epithelium-Derived Factor Contributes to Insulin Resistance in Obesity
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“, 2006) suggest that PEDF can be added to this list and supports the premise that the net balance between proangiogenic factors secreted from fibroblasts and anti-angiogenic factors secreted from mature adipocytes is important for appropriate vascularization during white adipose-tissue development (Cao, 2007).”
BackgroundInfluentialEctopic Fat, Insulin Resistance, and Nonalcoholic Fatty Liver Disease
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Steiner, B. M., & Berry, D. C. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.889923 · Cited by 171
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“Leptin also moderates angiogenesis under hypoxic conditions, it has direct effect on endothelium and also enhances VEGF production [54,55].”
BackgroundMalietzis, G. A., Aziz, O., Bagnall, N. M., Johns, N., Fearon, K. C. H., & Jenkins, J. T. (2014) · European Journal of Surgical Oncology · doi:10.1016/j.ejso.2014.10.056 · Cited by 177
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Psoriasis as a systemic disease
Grozdev, I., Korman, N. J., & Tsankov, N. (2013) · Clinics in Dermatology · doi:10.1016/j.clindermatol.2013.11.001 · Cited by 172
“VEGF is also increased in hyperinsulinemic states such as the metabolic syndrome, in which adipocytes are its primary source [91].”
BackgroundOkumura, S., Kaido, T., Hamaguchi, Y., Kobayashi, A., Shirai, H., Yao, S., Yagi, S., Kamo, N., Hatano, E., Okajima, H., et al. (2017) · Annals of Surgical Oncology · doi:10.1245/s10434-017-6077-y · Cited by 171
“Myocytes produce myokines and adipocytes produce adipokines (cytokines).(26,27) Visceral fat is functionally different from subcutaneous fat in the cytokine production profile.”
BackgroundNotch ligand Delta-like 4 blockade attenuates atherosclerosis and metabolic disorders
Fukuda, D., Aïkawa, E., Świrski, F. K., Novobrantseva, T. I., Koteliansky, V., Görgün, C. Z., Chudnovskiy, A., Yamazaki, H., Croce, K., Weissleder, R., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1116889109 · Cited by 171
“Dll4 blockade disrupts angiogenesis and inhibits cancer growth by induction of hypoxia (10–12), and evidence links angiogenesis with adipose tissue development (65), fat accumulation, and insulin resistance (66).”
BackgroundAngiogenesis in Adipose Tissue: The Interplay Between Adipose and Endothelial Cells
Herold, J. M., & Kalucka, J. M. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2020.624903 · Cited by 179
“This suggests an autoregulatory function for angiogenesis in AT (Cao, 2007).”
BackgroundHursting, S. D., & Dunlap, S. M. (2012) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2012.06737.x · Cited by 171
Jugran, A. K., Rawat, S., Devkota, H. P., BHATT, I. D., & Rawal, R. S. (2020) · Phytotherapy Research · doi:10.1002/ptr.6821 · Cited by 179
“Delayed wound healing has been known as a diabetes complication due to microangiopathy and endothelial dysfunction (Cao, 2007).”
BackgroundLadoire, S., Bonnetain, F., Gauthier, M., Zanetta, S., Petit, J., Guiu, S., Kermarrec, I., Mourey, E., Michel, F., Krause, D., et al. (2011) · The Oncologist · doi:10.1634/theoncologist.2010-0227 · Cited by 162
Brown adipose tissue derived VEGF-A modulates cold tolerance and energy expenditure
Sun, K., Kusminski, C. M., Luby‐Phelps, K., Spurgin, S. B., An, Y., Wang, Q. A., Holland, W. L., & Scherer, P. E. (2014) · Molecular Metabolism · doi:10.1016/j.molmet.2014.03.010 · Cited by 152
Han, T. T. Y., Toutounji, S., Amsden, B. G., & Flynn, L. E. (2015) · Biomaterials · doi:10.1016/j.biomaterials.2015.08.053 · Cited by 150
Angiogenesis, adipokines and breast cancer
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“There is also a complex relationship between adipose tissue and the process of angiogenesis, whereby fat cells synthesize angiogenic, largely protein, growth factors; conversely, neovascularization is an essential precursor to the formation of new adipose tissue [4].”
BackgroundAdipose Tissue Fibrosis: Mechanisms, Models, and Importance
DeBari, M. K., & Abbott, R. D. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21176030 · Cited by 153
“Both adipocytes and adipocyte progenitor cells produce angiogenic factors, such as vascular endothelial growth factor (VEGF), leptin, fibroblast growth factor 2 (FGF-2), and hepatocyte growth factor (HGF) [44,45].”
BackgroundThe role of adipose tissue senescence in obesity- and ageing-related metabolic disorders
Liu, Z., Wu, K. K.-L., Jiang, X. X., Xu, A., & Cheng, K. K. Y. (2020) · Clinical Science · doi:10.1042/cs20190966 · Cited by 148
Adipose tissue immunity and cancer
Catalán, V., Gómez‐Ambrosi, J., Rodríguez, A., & Frühbeck, G. (2013) · Frontiers in Physiology · doi:10.3389/fphys.2013.00275 · Cited by 140
“Angiogenesis is a physiological response that regulates adipogenesis representing a hallmark of tumor growth (Hanahan and Folkman, 1996; Carmeliet and Jain, 2000; Cao, 2007).”
BackgroundAmato, M. C., Pizzolanti, G., Torregrossa, V., Misiano, G., Milano, S., & Giordano, C. S. D. S. (2014) · PLoS ONE · doi:10.1371/journal.pone.0091969 · Cited by 135
“Lastly, it is also worth noting the significant association of VAI with VEGF and HGF, an expression of the fact that activated adipocytes produce multiple angiogenic factors including leptin, HGF, VEGF, which stimulate neovascularization during fat mass expansion [39].”
BackgroundGrowth Signals, Inflammation, and Vascular Perturbations
Hursting, S. D., & Hursting, M. J. (2012) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.111.241927 · Cited by 132
“These include VEGF, IGF-1, PAI-1, leptin, hepatocyte growth factor, and fibroblast growth factor-2.(52) In the obese, nontumor setting, these factors stimulate neovascularization in support of the expanding fat mass.”
BackgroundCalorie restriction and cancer prevention: a mechanistic perspective
Hursting, S. D., Dunlap, S. M., Ford, N. A., Hursting, M. J., & Lashinger, L. M. (2013) · Cancer & Metabolism · doi:10.1186/2049-3002-1-10 · Cited by 137
“In the obese, nontumor setting, these factors stimulate neovascularization in support of the expanding fat mass [69].”
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“The identification of ATGL as a putative receptor broadens the spectrum of potential PEDF targets, having implications in areas that bridge lipid metabolism and angiogenesis [26].”
BackgroundAngiogenesis Associated With Visceral and Subcutaneous Adipose Tissue in Severe Human Obesity
Ledoux, S., Quéguiner, I., Msika, S., Caldérari, S., Rufat, P., Gasc, J., Corvol, P. L., & Larger, É. (2008) · Diabetes · doi:10.2337/db07-1812 · Cited by 126
Adaptogenic herb ginseng (Panax) as medical food: Status quo and future prospects
Patel, S., & Rauf, A. (2017) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2016.11.112 · Cited by 126
Angiogenesis in diabetes and obesity
Cheng, R., & Ma, J. (2015) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-015-9310-7 · Cited by 131
“Higher capillary density is found in BAT, compared with that in WAT [124, 133].”
InfluentialAdipose Tissue Remodeling in Pathophysiology
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From obesity to cancer: a review on proposed mechanisms
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“Adipocytes secrete a variety of angiogenic factors (6), and our functional studies with conditioned medium raise the intriguing possibility that PV adipocytes may play a previously unrecognized but important role in promoting angiogenesis in the setting of atherosclerosis.”
BackgroundMethodKlimčáková, E., Roussel, B., Márquez-Quiñones, A., Kováčová, Z., Kováčiková, M., Combes, M., Šiklová, M., Hejnová, J., Šrámková, P., Bouloumié, A., et al. (2010) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2010-1575 · Cited by 122
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“Several independent studies show that Ang-2 is constitutively up-regulated in expanding adipose tissues (5, 21, 51).”
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Nanotechnology advances towards development of targeted-treatment for obesity
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Stem Cell Niches for Skin Regeneration
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“Adipogenic and angiogenic pathways appear to be concomitantly regulated and adipocytes secrete multiple cytokines that induce blood vessel formation including vascular endothelial-derived growth factor (VEGF), FGF2, BMP2, and MMPs [51, 52].”
BackgroundLeptin–cytokine crosstalk in breast cancer
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“Recruitment of inflammatory cells significantly contributes to adipose neovascularization and breast cancer inflammation and angiogenesis (Cao, 2007).”
Adipose Tissue Vascularization: Its Role in Chronic Inflammation
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“Angiogenesis is required for adipocyte differentiation and tissue growth [49, 50].”
Metadata
- Authors
- Cao, Y.
- Affiliations
- Karolinska Institutet (SE)
- Corresponding author
- Cao, Yihai
- ORCID
- Cao, Yihai
- Venue
- Journal of Clinical Investigation
- Published
- 2007-09-04
- Volume
- 117
- Issue
- 9
- Pages
- 2362-2368
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC1963348
- OpenAlex
- W2027442301
- Cited by
- 736
- References
- 120
- Citations by year
- 2026: 18 · 2025: 18 · 2024: 24 · 2023: 32 · 2022: 32 · 2021: 25 · 2020: 43 · 2019: 47 · 2018: 59 · 2017: 48 · 2016: 40 · 2015: 42 · 2014: 66 · 2013: 67 · 2012: 43
- FWCI
- 21.41
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Swedish Cancer Foundation
- European Commission
- Hjärt-Lungfonden
- Karolinska Institutet
- Vetenskapsrådet
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Keywords
- angiogenesis, adipogenesis, obesity, neovascularization, adipocytes, angiogenic factors, leptin, vascular endothelial growth factor, angiopoietins, paracrine signaling, anti-angiogenic therapy
- MeSH terms
- Animals, Cell Communication, Humans, Neovascularization, Pathologic, Obesity, Adipocytes, Endothelial Cells, Angiogenesis Inducing Agents, Adipogenesis
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