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Reducing VEGFB expression regulates the balance of glucose and lipid metabolism in mice via VEGFR1

Luo, Xu, Li, Rong-Rong, Li, Yu-Qi, Yu, Han-Pu, Yu, Hai-Ning, Jiang, Wen-Guo, Li, Ya-Na·2022·Molecular Medicine Reports
DOI 10.3892/mmr.2022.12801PMC PMC9366154
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Figure 1. Systemic VEGFB-knockdown mouse model construction and genetic identification. (A) VEGFB gene structure, gRNA target site and deletion region. Boxes and lines respectively represent exons and introns. F1 and R1 arrows indicate the position of primers for PCR genotyping. 1–7 shows the VEGFB gene sequence, where the red line represents the VEGFB knockout gene sequence. (B-E) Western blot analysis of VEGFB protein in liver tissues and pancreas. (F and G) mRNA analysis in the liver tissues and pancreas. **P<0.01 vs. VEGFB+/+ group and ***P<0.001 vs. VEGFB+/+ group. VEGFB, vascular endothelial growth factor B.
Figure 1. Systemic VEGFB-knockdown mouse model construction and genetic identification. (A) VEGFB gene structure, gRNA target site and deletion region. Boxes and lines respectively represent exons and introns. F1 and R1 arrows indicate the position of primers for PCR genotyping. 1–7 shows the VEGFB gene sequence, where the red line represents the VEGFB knockout gene sequence. (B-E) Western blot analysis of VEGFB protein in liver tissues and pancreas. (F and G) mRNA analysis in the liver tissues and pancreas. **P<0.01 vs. VEGFB+/+ group and ***P<0.001 vs. VEGFB+/+ group. VEGFB, vascular endothelial growth factor B.CC BY-NC-ND · PubMed Central
Figure 2. Effect of VEGFB downregulation on liver and pancreas. (A) Body weight curve of mice (4–32 weeks). (B) Food intake curve of mice (4–32 weeks) (C and D) Organ coefficient ratio between liver and pancreas in mice. (E) Light microscopic structure of liver and pancreas; a and b: VEGFB+/+ group, c and d: VEGFB-/- group (scale bar, 50 µm; magnification, ×400). (F) Electron microscopic structure of liver and pancreas; a and b: VEGFB+/+ group, c and d: VEGFB-/- group (scale bar, 1 µm; images a and c, ×15,000 magnification; images b and d, ×8,000 magnification). (G and H) Density of mature and immature vesicles. ***P<0.001 vs. VEGFB+/+ group. VEGFB, vascular endothelial growth factor B.
Figure 2. Effect of VEGFB downregulation on liver and pancreas. (A) Body weight curve of mice (4–32 weeks). (B) Food intake curve of mice (4–32 weeks) (C and D) Organ coefficient ratio between liver and pancreas in mice. (E) Light microscopic structure of liver and pancreas; a and b: VEGFB+/+ group, c and d: VEGFB-/- group (scale bar, 50 µm; magnification, ×400). (F) Electron microscopic structure of liver and pancreas; a and b: VEGFB+/+ group, c and d: VEGFB-/- group (scale bar, 1 µm; images a and c, ×15,000 magnification; images b and d, ×8,000 magnification). (G and H) Density of mature and immature vesicles. ***P<0.001 vs. VEGFB+/+ group. VEGFB, vascular endothelial growth factor B.CC BY-NC-ND · PubMed Central
Figure 3. Effect of VEGFB downregulation on serum glucose and lipid metabolism. (A) Total cholesterol. (B) Triglycerides. (C) Low density lipoprotein-cholesterol (D) High density lipoprotein-cholesterol. (E) Fasting blood glucose. (F) Postprandial blood glucose. (G) HbA1c. (H) Serum glucose level. **P<0.01 vs. VEGFB+/+ group and ***P<0.001 vs. VEGFB+/+ group. VEGFB, vascular endothelial growth factor B.
Figure 3. Effect of VEGFB downregulation on serum glucose and lipid metabolism. (A) Total cholesterol. (B) Triglycerides. (C) Low density lipoprotein-cholesterol (D) High density lipoprotein-cholesterol. (E) Fasting blood glucose. (F) Postprandial blood glucose. (G) HbA1c. (H) Serum glucose level. **P<0.01 vs. VEGFB+/+ group and ***P<0.001 vs. VEGFB+/+ group. VEGFB, vascular endothelial growth factor B.CC BY-NC-ND · PubMed Central
Figure 4. Effect of VEGFB downregulation on blood glucose balance and insulin resistance. (A) OGTT. (B) Area under the curve in OGTT. (C) IPITT. (D) Area under the curve in IPTT. (E) Fasting insulin. (F) Serum glucagon. (G) HOMA-IR. (H) HOMA-β. *P<0.05 vs. VEGFB+/+ group, **P<0.01 vs. VEGFB+/+ group and ***P<0.001 vs. VEGFB+/+ group. HOMA-IR, insulin resistance index; HOMA-β, pancreatic β-cell secretion index. VEGFB, vascular endothelial growth factor B.
Figure 4. Effect of VEGFB downregulation on blood glucose balance and insulin resistance. (A) OGTT. (B) Area under the curve in OGTT. (C) IPITT. (D) Area under the curve in IPTT. (E) Fasting insulin. (F) Serum glucagon. (G) HOMA-IR. (H) HOMA-β. *P<0.05 vs. VEGFB+/+ group, **P<0.01 vs. VEGFB+/+ group and ***P<0.001 vs. VEGFB+/+ group. HOMA-IR, insulin resistance index; HOMA-β, pancreatic β-cell secretion index. VEGFB, vascular endothelial growth factor B.CC BY-NC-ND · PubMed Central
Figure 5. Expression of VEGFR1 and NRP1 in the liver and islets after VEGFB downregulation. (A) Dithizone staining to identify islet cells (magnification, ×400). (B) Numbers of islets. (C-H) Western blot analysis of VEGFB and NRP1 protein in liver tissues and islets. (I-L) mRNA analysis of VEGFB and NRP1 in liver tissues and islets. *P<0.05 vs. VEGFB+/+ group, **P<0.01 vs. VEGFB+/+ group and ***P<0.001 vs. VEGFB+/+ group. VEGFB, vascular endothelial growth factor B; NRP1, neuropilin-1.
Figure 5. Expression of VEGFR1 and NRP1 in the liver and islets after VEGFB downregulation. (A) Dithizone staining to identify islet cells (magnification, ×400). (B) Numbers of islets. (C-H) Western blot analysis of VEGFB and NRP1 protein in liver tissues and islets. (I-L) mRNA analysis of VEGFB and NRP1 in liver tissues and islets. *P<0.05 vs. VEGFB+/+ group, **P<0.01 vs. VEGFB+/+ group and ***P<0.001 vs. VEGFB+/+ group. VEGFB, vascular endothelial growth factor B; NRP1, neuropilin-1.CC BY-NC-ND · PubMed Central
Figure 6. Expression of VEGFA and VEGFR2 in the liver and islets after VEGFB downregulation. (A-F) Western blot analysis of VEGFA and VEGFR2 protein in liver tissues and islets. (B) Numbers of islets. (G-J) mRNA analysis of VEGFA and VEGFR2 in liver tissues and islets. *P<0.05 vs. VEGFB+/+ group, **P<0.01 vs. VEGFB+/+ group and ***P<0.001 vs. VEGFB+/+ group.
Figure 6. Expression of VEGFA and VEGFR2 in the liver and islets after VEGFB downregulation. (A-F) Western blot analysis of VEGFA and VEGFR2 protein in liver tissues and islets. (B) Numbers of islets. (G-J) mRNA analysis of VEGFA and VEGFR2 in liver tissues and islets. *P<0.05 vs. VEGFB+/+ group, **P<0.01 vs. VEGFB+/+ group and ***P<0.001 vs. VEGFB+/+ group.CC BY-NC-ND · PubMed Central
Figure 7. Mechanism of VEGFB involved in insulin secretion of β-cells. VEGFB, vascular endothelial growth factor B.
Figure 7. Mechanism of VEGFB involved in insulin secretion of β-cells. VEGFB, vascular endothelial growth factor B.CC BY-NC-ND · PubMed Central

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Research works printed but not linked: 50

  1. Stumvoll, 2005, Type 2 diabetes: Principles of pathogenesis and therapy, Lancet, 365, 1333, 10.1016/S0140-6736(05)61032-X · DOI · Paper page
  2. Lysaght, 2011, Pro-inflammatory and tumour proliferative properties of excess visceral adipose tissue, Cancer Lett, 312, 62, 10.1016/j.canlet.2011.07.034 · DOI
  3. Bai, 2020, Inhibition of ferroptosis alleviates atherosclerosis through attenuating lipid peroxidation and endothelial dysfunction in mouse aortic endothelial cell, Free Radic Biol Med, 160, 92, 10.1016/j.freeradbiomed.2020.07.026 · DOI
  4. Sinha, 2019, Nonalcoholic fatty liver disease and hypercholesterolemia: Roles of thyroid hormones, metabolites, and agonists, Thyroid, 29, 1173, 10.1089/thy.2018.0664 · DOI
  5. Laakso, 2014, Insulin resistance and hyperglycaemia in cardiovascular disease development, Nat Rev Endocrinol, 10, 293, 10.1038/nrendo.2014.29 · DOI
  6. Khan, 2019, From pre-diabetes to diabetes: Diagnosis, treatments and translational research, Medicina (Kaunas), 55, 546, 10.3390/medicina55090546 · DOI · Paper page
  7. Aase, 1999, Localization of VEGF-B in the mouse embryo suggests a paracrine role of the growth factor in the developing vasculature, Dev Dyn, 215, 12, 10.1002/(SICI)1097-0177(199905)215:1<12::AID-DVDY3>3.0.CO;2-N · DOI
  8. Hagberg, 2012, Targeting VEGF-B as a novel treatment for insulin resistance and type 2 diabetes, Nature, 490, 426, 10.1038/nature11464 · DOI
  9. Robciuc, 2016, VEGFB/VEGFR1-Induced expansion of adipose vasculature counteracts obesity and related metabolic complications, Cell Metab, 23, 712, 10.1016/j.cmet.2016.03.004 · DOI
  10. Hagberg, 2010, Vascular endothelial growth factor B controls endothelial fatty acid uptake, Nature, 464, 917, 10.1038/nature08945 · DOI
  11. Wagenmakers, 2016, Increased muscle blood supply and transendothelial nutrient and insulin transport induced by food intake and exercise: Effect of obesity and ageing, J Physiol, 594, 2207, 10.1113/jphysiol.2014.284513 · DOI · Paper page
  12. Falkevall, 2017, Reducing VEGF-B signaling ameliorates renal lipotoxicity and protects against diabetic kidney disease, Cell Metab, 25, 713, 10.1016/j.cmet.2017.01.004 · DOI
  13. Moessinger, 2020, VEGF-B signaling impairs endothelial glucose transcytosis by decreasing membrane cholesterol content, EMBO Rep, 21, e49343, 10.15252/embr.201949343 · DOI · Paper page
  14. Jensen, 2020, VEGF-B ablation in pancreatic β-cells upregulates insulin expression without affecting glucose homeostasis or islet lipid uptake, Sci Rep, 10, 923, 10.1038/s41598-020-57599-2 · DOI
  15. Shibuya, 2015, VEGF-VEGFR system as a target for suppressing inflammation and other diseases, Endocr Metab Immune Disord Drug Targets, 15, 135, 10.2174/1871530315666150316121956 · DOI
  16. Zachary, 2001, Signaling transduction mechanisms mediating biological actions of the vascular endothelial growth factor family, Cardiovasc Res, 49, 568, 10.1016/S0008-6363(00)00268-6 · DOI
  17. Shen, 2018, VEGFB-VEGFR1 ameliorates Ang II-induced cardiomyocyte hypertrophy through Ca2+-mediated PKG I pathway, J Cell Biochem, 119, 1511, 10.1002/jcb.26311 · DOI
  18. Hu, 2021, Vascular endothelial growth factor B exerts lipid-lowering effect by activating AMPK via VEGFR1, Life Sci, 276, 119401, 10.1016/j.lfs.2021.119401 · DOI
  19. Livak, 2001, Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method, Methods, 25, 402, 10.1006/meth.2001.1262 · DOI · Paper page
  20. Claesson-Welsh, 2016, VEGF receptor signal transduction-A brief update, Vascul Pharmacol, 86, 14, 10.1016/j.vph.2016.05.011 · DOI
  21. Ferrara, 2003, The biology of VEGF and its receptors, Nat Med, 9, 669, 10.1038/nm0603-669 · DOI · Paper page
  22. Bates, 2010, Vascular endothelial growth factors and vascular permeability, Cardiovasc Res, 87, 262, 10.1093/cvr/cvq105 · DOI
  23. Osawa, 2011, Increased expression of histone demethylase JHDM1D under nutrient starvation suppresses tumor growth via down-regulating angiogenesis, Proc Natl Acad Sci USA, 108, 20725, 10.1073/pnas.1108462109 · DOI
  24. Mehlem, 2016, PGC-1α coordinates mitochondrial respiratory capacity and muscular fatty acid uptake via regulation of VEGF-B, Diabetes, 65, 861, 10.2337/db15-1231 · DOI
  25. Wu, 2017, Plasma vascular endothelial growth factor B levels are increased in patients with newly diagnosed type 2 diabetes mellitus and associated with the first phase of glucose-stimulated insulin secretion function of β-cell, J Endocrinol Invest, 40, 1219, 10.1007/s40618-017-0677-z · DOI
  26. Kivelä, 2014, VEGF-B-induced vascular growth leads to metabolic reprogramming and ischemia resistance in the heart, EMBO Mol Med, 6, 307, 10.1002/emmm.201303147 · DOI
  27. Samuel, 2010, Lipid-induced insulin resistance: Unravelling the mechanism, Lancet, 375, 2267, 10.1016/S0140-6736(10)60408-4 · DOI · Paper page
  28. Louzier, 2003, Role of VEGF-B in the lung during development of chronic hypoxic pulmonary hypertension, Am J Physiol Lung Cell Mol Physiol, 284, L926, 10.1152/ajplung.00247.2002 · DOI
  29. Reichelt, 2003, Vascular endothelial growth factor-B and retinal vascular development in the mouse, Clin Exp Ophthalmol, 31, 61, 10.1046/j.1442-9071.2003.00602.x · DOI
  30. Sun, 2014, Clinical association of circulating VEGF-B levels with hyperlipidemia and target organ damage in type 2 diabetic patients, J Biol Regul Homeost Agents, 28, 225
  31. Shen, 2021, VEGF-B antibody and interleukin-22 fusion protein ameliorates diabetic nephropathy through inhibiting lipid accumulation and inflammatory responses, Acta Pharm Sin B, 11, 127, 10.1016/j.apsb.2020.07.002 · DOI
  32. Cheng, 2016, Serum vascular endothelial growth factor B is elevated in women with polycystic ovary syndrome and can be decreased with metformin treatment, Clin Endocrinol (Oxf), 84, 386, 10.1111/cen.12950 · DOI
  33. Abdul Razak, 2019, The importance of measurement of plasma fibrinogen level among patients with type-2 diabetes mellitus, Diabetes Metab Syndr, 13, 1151, 10.1016/j.dsx.2019.01.049 · DOI
  34. Lam, 2012, The worldwide diabetes epidemic, Curr Opin Endocrinol Diabetes Obes, 19, 93, 10.1097/MED.0b013e328350583a · DOI
  35. Clayton, 2008, Bulk synaptic vesicle endocytosis is rapidly triggered during strong stimulation, J Neurosci, 28, 6627, 10.1523/JNEUROSCI.1445-08.2008 · DOI
  36. Zhao, 2010, Gαo represses insulin secretion by reducing vesicular docking in pancreatic beta-cells, Diabetes, 59, 2522, 10.2337/db09-1719 · DOI
  37. Pan, 2016, Regulation of L-type Ca2+ channel activity and insulin secretion by huntingtin-associated protein 1, J Biol Chem, 291, 26352, 10.1074/jbc.M116.727990 · DOI
  38. Wollam, 2017, Chromogranin A regulates vesicle storage and mitochondrial dynamics to influence insulin secretion, Cell Tissue Res, 368, 487, 10.1007/s00441-017-2580-5 · DOI
  39. Vakilian, 2019, A review on insulin trafficking and exocytosis, Gene, 706, 52, 10.1016/j.gene.2019.04.063 · DOI
  40. Nash, 2006, The biology of vascular endothelial growth factor-B (VEGF-B), Pulm Pharmacol Ther, 19, 61, 10.1016/j.pupt.2005.02.007 · DOI
  41. Gilbert, 2008, Islet oxygen consumption and insulin secretion tightly coupled to calcium derived from L-type calcium channels but not from the endoplasmic reticulum, J Biol Chem, 283, 24334, 10.1074/jbc.M802097200 · DOI
  42. Gauthier, 2008, Synaptotagmins bind calcium to release insulin, Am J Physiol Endocrinol Metab, 295, E1279, 10.1152/ajpendo.90568.2008 · DOI
  43. Shang, 2021, Cardiac-specific VEGFB overexpression reduces lipoprotein lipase activity and improves insulin action in rat heart, Am J Physiol Endocrinol Metab, 321, E753, 10.1152/ajpendo.00219.2021 · DOI
  44. Anisimov, 2013, The basis for the distinct biological activities of vascular endothelial growth factor receptor-1 ligands, Sci Signal, 6, ra52, 10.1126/scisignal.2003905 · DOI
  45. Bry, 2014, Vascular endothelial growth factor-B in physiology and disease, Physiol Rev, 94, 779, 10.1152/physrev.00028.2013 · DOI
  46. Rafii, 2016, VEGF-B improves metabolic health through vascular pruning of fat, Cell Metab, 23, 571, 10.1016/j.cmet.2016.03.012 · DOI
  47. Feng, 2017, Mechanical activation of hypoxia-inducible factor 1α drives endothelial dysfunction at atheroprone sites, Arterioscler Thromb Vasc Biol, 37, 2087, 10.1161/ATVBAHA.117.309249 · DOI
  48. Liu, 2016, Smooth muscle hypoxia-inducible factor 1α links intravascular pressure and atherosclerosis-brief report, Arterioscler Thromb Vasc Biol, 36, 442, 10.1161/ATVBAHA.115.306861 · DOI
  49. Ghorbanzadeh, 2016, Effects of crocin and voluntary exercise, alone or combined, on heart VEGF-A and HOMA-IR of HFD/STZ induced type 2 diabetic rats, J Endocrinol Invest, 39, 1179, 10.1007/s40618-016-0456-2 · DOI
  50. Jin, 2018, VEGF and VEGFB play balancing roles in adipose differentiation, gene expression, and function, Endocrinology, 159, 2036, 10.1210/en.2017-03246 · DOI

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Metadata

Authors
Luo, X., Li, R.-R., Li, Y.-Q., Yu, H.-P., Yu, H.-N., Jiang, W.-G., & Li, Y.-N.
Affiliations
  • Department of Pathophysiology, School of Basic Medicine, Binzhou Medical University, Yantai, Shandong 264003, P.R. China
  • Clinical Medicine, School of Basic Medicine, Binzhou Medical University, Yantai, Shandong 264003, P.R. China
  • Department of Stomatology Medicine, School of Oral Medicine, Binzhou Medical University, Yantai, Shandong 264003, P.R. China
  • Department of Pharmacy, Binzhou Medical University, Yantai, Shandong 264003, P.R. China
Venue
Molecular Medicine Reports
Publisher
Spandidos Publications
Published
2022-07-26
Volume
26
Issue
3
ISSN
  • 1791-2997
  • 1791-3004
DOI
10.3892/mmr.2022.12801
PMC
PMC9366154
Cited by
19
References
2

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CoChat. (2026). Citation check: Reducing VEGFB expression regulates the balance of glucose and lipid metabolism in mice via VEGFR1. https://app.cochat.ai/papers/10.3892/mmr.2022.12801
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Luo, X., Li, R.-R., Li, Y.-Q., Yu, H.-P., Yu, H.-N., Jiang, W.-G., & Li, Y.-N. (2022). Reducing VEGFB expression regulates the balance of glucose and lipid metabolism in mice via VEGFR1. Molecular Medicine Reports. https://doi.org/10.3892/mmr.2022.12801