Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
European Journal of Nutrition
Published in: European Journal of Nutrition 2/2017

01-03-2017 | Original Contribution

Methylation patterns of Vegfb promoter are associated with gene and protein expression levels: the effects of dietary fatty acids

Authors: Roberto Monastero, Sara García-Serrano, Ana Lago-Sampedro, Francisca Rodríguez-Pacheco, Natalia Colomo, Sonsoles Morcillo, Gracia M. Martín-Nuñez, Juan M. Gomez-Zumaquero, Eduardo García-Fuentes, Federico Soriguer, Gemma Rojo-Martínez, Eva García-Escobar

Published in: European Journal of Nutrition | Issue 2/2017

Login to get access

Abstract

Purpose

We have investigated the epigenetic regulation by dietary fatty acids of Vegfb levels in rats’ white adipose tissue and 3T3-L1 cells.

Methods

A group of rats were assigned to three diets, each one with a different composition of saturated, monounsaturated and polyunsaturated fatty acids. Samples of white adipose tissues were taken for the methylation and expression studies. Additionally, 3T3-L1 cells were treated with palmitic, oleic, and linoleic fatty acids. After treatment, cells were harvested and genetic material was extracted for the analysis of Vegfb levels.

Results

We report evidence of changes in the methylation levels of the CpG island at the Vegfb promoter and in the Vegfb expression levels in vivo and in vitro by dietary fatty acid, with the main contribution of the linoleic fatty acid. Vegfb promoter methylation levels were closely related to the Vegfb gene expression.

Conclusion

According to our results, the regulation of Vegfb gene expression by dietary fatty acids may be mediated, at least in part, by epigenetic modifications on Vegfb promoter methylation. Considering the deep association between angiogenesis and tissue growth, we suggest the nutriepigenetic regulation of Vegfb as a key target in the control of the adipose tissue expansion.
Appendix
Available only for authorised users
Literature
1.
Boden G, Chen X, Iqbal N (1998) Acute lowering of plasma fatty acids lowers basal insulin secretion in diabetic and nondiabetic subjects. Diabetes 47(10):1609–1612CrossRef
2.
Clore JN, Allred J, White D, Li J, Stillman J (2002) The role of plasma fatty acid composition in endogenous glucose production in patients with type 2 diabetes mellitus. Metabolism 51(11):1471–1477CrossRef
3.
Eckardt K, Taube A, Eckel J (2011) Obesity-associated insulin resistance in skeletal muscle: role of lipid accumulation and physical inactivity. Rev Endocr Metab Disord 12(3):163–172CrossRef
4.
Hagberg CE, Falkevall A, Wang X, Larsson E, Huusko J, Nilsson I et al (2010) Vascular endothelial growth factor B controls endothelial fatty acid uptake. Nature 464(7290):917–921CrossRef
5.
Li X, Tjwa M, Van Hove I, Enholm B, Neven E, Paavonen K et al (2008) Reevaluation of the role of VEGF-B suggests a restricted role in the revascularization of the ischemic myocardium. Arterioscler Thromb Vasc Biol 28(9):1614–1620CrossRef
6.
Hagberg CE, Mehlem A, Falkevall A, Muhl L, Fam BC, Ortsater H et al (2012) Targeting VEGF-B as a novel treatment for insulin resistance and type 2 diabetes. Nature 490(7420):426–430CrossRef
7.
Gealekman O, Burkart A, Chouinard M, Nicoloro SM, Straubhaar J, Corvera S (2008) Enhanced angiogenesis in obesity and in response to PPARgamma activators through adipocyte VEGF and ANGPTL4 production. Am J Physiol Endocrinol Metab 295(5):E1056–E1064CrossRef
8.
Bry M, Kivela R, Holopainen T, Anisimov A, Tammela T, Soronen J et al (2010) Vascular endothelial growth factor-B acts as a coronary growth factor in transgenic rats without inducing angiogenesis, vascular leak, or inflammation. Circulation 122(17):1725–1733CrossRef
9.
Karpanen T, Bry M, Ollila HM, Seppanen-Laakso T, Liimatta E, Leskinen H et al (2008) Overexpression of vascular endothelial growth factor-B in mouse heart alters cardiac lipid metabolism and induces myocardial hypertrophy. Circ Res 103(9):1018–1026CrossRef
10.
Feil R, Fraga MF (2011) Epigenetics and the environment: emerging patterns and implications. Nat Rev Genet 13(2):97–109
11.
Shen W, Wang C, Xia L, Fan C, Dong H, Deckelbaum RJ et al (2014) Epigenetic modification of the leptin promoter in diet-induced obese mice and the effects of N-3 polyunsaturated fatty acids. Sci Rep 4:5282
12.
Burdge GC, Lillycrop KA (2010) Bridging the gap between epigenetics research and nutritional public health interventions. Genome Med 2(11):80CrossRef
13.
Gabory A, Attig L, Junien C (2011) Developmental programming and epigenetics. Am J Clin Nutr 94(6 Suppl):1943S–1952SCrossRef
14.
Simmons R (2011) Epigenetics and maternal nutrition: nature v. nurture. Proc Nutr Soc 70(1):73–81CrossRef
15.
Matouk CC, Marsden PA (2008) Epigenetic regulation of vascular endothelial gene expression. Circ Res 102(8):873–887CrossRef
16.
Hellebrekers DM, Melotte V, Vire E, Langenkamp E, Molema G, Fuks F et al (2007) Identification of epigenetically silenced genes in tumor endothelial cells. Cancer Res 67(9):4138–4148CrossRef
17.
Vallim T, Salter AM (2010) Regulation of hepatic gene expression by saturated fatty acids. Prostaglandins Leukot Essent Fatty Acids 82(4–6):211–218CrossRef
18.
Salter AM, Tarling EJ (2007) Regulation of gene transcription by fatty acids. Animal 1(9):1314–1320CrossRef
19.
Liang H, Zhong Y, Zhou S, Li QQ (2011) Palmitic acid-induced apoptosis in pancreatic beta-cells is increased by liver X receptor agonist and attenuated by eicosapentaenoate. In Vivo 25(5):711–718
20.
Margareto J, Marti A, Martinez JA (2001) Modification of RXRalpha expression according to the duration of a cafeteria diet. J Physiol Biochem 57(4):347–348CrossRef
21.
Sabin MA, Crowne EC, Stewart CE, Hunt LP, Turner SJ, Welsh GI et al (2007) Depot-specific effects of fatty acids on lipid accumulation in children’s adipocytes. Biochem Biophys Res Commun 361(2):356–361CrossRef
22.
Hommelberg PP, Plat J, Langen RC, Schols AM, Mensink RP (2009) Fatty acid-induced NF-kappaB activation and insulin resistance in skeletal muscle are chain length dependent. Am J Physiol Endocrinol Metab 296(1):E114–E120CrossRef
23.
Dimopoulos N, Watson M, Sakamoto K, Hundal HS (2006) Differential effects of palmitate and palmitoleate on insulin action and glucose utilization in rat L6 skeletal muscle cells. Biochem J 399(3):473–481CrossRef
24.
Burdge GC, Lillycrop KA (2014) Fatty acids and epigenetics. Curr Opin Clin Nutr Metab Care 17(2):156–161CrossRef
25.
Reeves PG, Nielsen FH, Fahey GC Jr (1993) AIN-93 purified diets for laboratory rodents: final report of the American Institute of Nutrition ad hoc writing committee on the reformulation of the AIN-76A rodent diet. J Nutr 123(11):1939–1951
26.
Soriguer F, Rojo-Martinez G, Dobarganes MC, Garcia Almeida JM, Esteva I, Beltran M et al (2003) Hypertension is related to the degradation of dietary frying oils. Am J Clin Nutr 78(6):1092–1097
27.
Mikeska T, Felsberg J, Hewitt CA, Dobrovic A (2011) Analysing DNA methylation using bisulphite pyrosequencing. Methods Mol Biol 791:33–53CrossRef
28.
Colyer HA, Armstrong RN, Sharpe DJ, Mills KI (2012) Detection and analysis of DNA methylation by pyrosequencing. Methods Mol Biol 863:281–292CrossRef
29.
Soriguer F, Garcia-Serrano S, Garrido-Sanchez L, Gutierrez-Repiso C, Rojo-Martinez G, Garcia-Escobar E et al (2010) Jejunal wall triglyceride concentration of morbidly obese persons is lower in those with type 2 diabetes mellitus. J Lipid Res 51(12):3516–3523CrossRef
30.
Altman DG (1990) Practical statistics for medical research, vol 91. Chapman & Hall, London, pp 218–223
31.
Oster B, Linnet L, Christensen LL, Thorsen K, Ongen H, Dermitzakis ET et al (2013) Non-CpG island promoter hypomethylation and miR-149 regulate the expression of SRPX2 in colorectal cancer. Int J Cancer 132(10):2303–2315CrossRef
32.
Xu H, Dong X, Ai Q, Mai K, Xu W, Zhang Y et al (2014) Regulation of tissue LC-PUFA contents, Delta6 fatty acyl desaturase (FADS2) gene expression and the methylation of the putative FADS2 gene promoter by different dietary fatty acid profiles in Japanese seabass (Lateolabrax japonicus). PLoS ONE 9(1):e87726CrossRef
33.
Kiec-Wilk B, Razny U, Mathers JC, Dembinska-Kiec A (2009) DNA methylation, induced by beta-carotene and arachidonic acid, plays a regulatory role in the pro-angiogenic VEGF-receptor (KDR) gene expression in endothelial cells. J Physiol Pharmacol 60(4):49–53
34.
Lomba A, Martinez JA, Garcia-Diaz DF, Paternain L, Marti A, Campion J et al (2010) Weight gain induced by an isocaloric pair-fed high fat diet: a nutriepigenetic study on FASN and NDUFB6 gene promoters. Mol Genet Metab 101(2–3):273–278CrossRef
35.
Voisin S, Almen MS, Moschonis G, Chrousos GP, Manios Y, Schioth HB (2014) Dietary fat quality impacts genome-wide DNA methylation patterns in a cross-sectional study of Greek preadolescents. Eur J Hum Genet 23(5):654–662CrossRef
36.
Lillycrop KA, Burdge GC (2011) Epigenetic changes in early life and future risk of obesity. Int J Obes (Lond) 35(1):72–83CrossRef
37.
Zhang J, Zhang F, Didelot X, Bruce KD, Cagampang FR, Vatish M, Hanson M, Lehnert H et al (2009) Maternal high fat diet during pregnancy and lactation alters hepatic expression of insulin like growth factor-2 and key microRNAs in the adult offspring. BMC Genom 10:478CrossRef
38.
Klein ME, Lioy DT, Ma L, Impey S, Mandel G, Goodman RH (2007) Homeostatic regulation of MeCP2 expression by a CREB-induced microRNA. Nat Neurosci 10:1513–1514CrossRef
39.
Varambally S, Cao Q, Mani RS, Shankar S, Wang X, Ateeq B, Laxman B, Cao X et al (2008) Genomic loss of microRNA-101 leads to overexpression of histone methyltransferase EZH2 in cancer. Science 322:1695–1699CrossRef
40.
Garcia-Serrano S, Moreno-Santos I, Garrido-Sanchez L, Gutierrez-Repiso C, Garcia-Almeida JM, Garcia-Arnes J, Rivas-Marin J, Gallego-Perales JL et al (2011) Stearoyl-CoA desaturase-1 is associated with insulin resistance in morbidly obese subjects. Mol Med 17:273–280CrossRef
41.
Rasouli N, Yao-Borengasser A, Miles LM, Elbein SC, Kern PA (2006) Increased plasma adiponectin in response to pioglitazone does not result from increased gene expression. Am J Physiol Endocrinol Metab 290:E42–E46CrossRef
42.
Hojbjerre L, Rosenzweig M, Dela F, Bruun JM, Stallknecht B (2007) Acute exercise increases adipose tissue interstitial adiponectin concentration in healthy overweight and lean subjects. Eur J Endocrinol 157:613–623CrossRef
43.
Kiunga GA, Raju J, Sabljic N, Bajaj G, Good CK, Bird RP (2004) Elevated insulin receptor protein expression in experimentally induced colonic tumors. Cancer Lett 211:145–153CrossRef
44.
Sotiropoulos KB, Clermont A, Yasuda Y, Rask-Madsen C, Mastumoto M, Takahashi J et al (2006) Adipose-specific effect of rosiglitazone on vascular permeability and protein kinase C activation: novel mechanism for PPARgamma agonist’s effects on edema and weight gain. FASEB J 20(8):1203–1205CrossRef
45.
Bouloumie A, Lolmede K, Sengenes C, Galitzky J, Lafontan M (2002) Angiogenesis in adipose tissue. Ann Endocrinol (Paris) 63(2 Pt 1):91–95
46.
Neels JG, Thinnes T, Loskutoff DJ (2004) Angiogenesis in an in vivo model of adipose tissue development. FASEB J 18(9):983–985
47.
Iggman D, Rosqvist F, Larsson A, Arnlov J, Beckman L, Rudling M et al (2014) Role of dietary fats in modulating cardiometabolic risk during moderate weight gain: a randomized double-blind overfeeding trial (LIPOGAIN study). J Am Heart Assoc 3(5):e001095CrossRef
48.
Bjermo H, Iggman D, Kullberg J, Dahlman I, Johansson L, Persson L et al (2012) Effects of n-6 PUFAs compared with SFAs on liver fat, lipoproteins, and inflammation in abdominal obesity: a randomized controlled trial. Am J Clin Nutr 95(5):1003–1012CrossRef
49.
Martin-Nunez GM, Rubio-Martin E, Cabrera-Mulero R, Rojo-Martinez G, Olveira G, Valdes S, Soriguer F, Castano L et al (2014) Type 2 diabetes mellitus in relation to global LINE-1 DNA methylation in peripheral blood: a cohort study. Epigenetics 9:1322–1328CrossRef
50.
Martin-Nunez GM, Cabrera-Mulero R, Rubio-Martin E, Rojo-Martinez G, Olveira G, Valdes S, Soriguer F, Castano L et al (2014) Methylation levels of the SCD1 gene promoter and LINE-1 repeat region are associated with weight change: an intervention study. Mol Nutr Food Res 58:1528–1536CrossRef
51.
Nicoletti CF, Nonino CB, de Oliveira BA, Pinhel MA, Mansego ML, Milagro FI, Zulet MA, Martinez JA (2015) DNA methylation and hydroxymethylation levels in relation to two weight loss strategies: energy-restricted diet or bariatric surgery. Obes Surg. doi:10.​1007/​s11695-015-1802-8
52.
Sanchez I, Reynoso-Camacho R, Salgado LM (2015) The diet-induced metabolic syndrome is accompanied by whole-genome epigenetic changes. Genes Nutr 10:471CrossRef
53.
Pan H, Lin X, Wu Y, Chen L, Teh AL, Soh SE, Lee YS, Tint MT, MacIsaac JL, Morin AM, Tan KH, Yap F, Saw SM, Kobor MS, Meaney MJ, Godfrey KM, Chong YS, Gluckman PD, Karnani N, Holbrook JD, GUSTO Study Group (2015) HIF3A association with adiposity: the story begins before birth. Epigenomics 7(6):937–950CrossRef
54.
Tajuddin SM, Amaral AF, Fernandez AF, Rodriguez-Rodero S, Rodriguez RM, Moore LE, Tardon A, Carrato A et al (2013) Genetic and non-genetic predictors of LINE-1 methylation in leukocyte DNA. Environ Health Perspect 121:650–656
55.
Hsieh CL (1994) Dependence of transcriptional repression on CpG methylation density. Mol Cell Biol 14:5487–5494CrossRef
56.
Boyes J, Bird A (1992) Repression of genes by DNA methylation depends on CpG density and promoter strength: evidence for involvement of a methyl-CpG binding protein. EMBO J 11:327–333
57.
Mill J, Heijmans BT (2013) From promises to practical strategies in epigenetic epidemiology. Nat Rev Genet 14:585–594CrossRef
Metadata
Title
Methylation patterns of Vegfb promoter are associated with gene and protein expression levels: the effects of dietary fatty acids
Authors
Roberto Monastero
Sara García-Serrano
Ana Lago-Sampedro
Francisca Rodríguez-Pacheco
Natalia Colomo
Sonsoles Morcillo
Gracia M. Martín-Nuñez
Juan M. Gomez-Zumaquero
Eduardo García-Fuentes
Federico Soriguer
Gemma Rojo-Martínez
Eva García-Escobar
Publication date
01-03-2017
Publisher
Springer Berlin Heidelberg
Published in
European Journal of Nutrition / Issue 2/2017
Print ISSN: 1436-6207
Electronic ISSN: 1436-6215
DOI
https://doi.org/10.1007/s00394-015-1115-7

Other articles of this Issue 2/2017

European Journal of Nutrition 2/2017 Go to the issue

Original Contribution

The efficacy of early iron supplementation on postpartum depression, a randomized double-blind placebo-controlled trial

Original Contribution

Increased dietary levels of α-linoleic acid inhibit mammary tumor growth and metastasis

Original Contribution

Effects of proanthocyanidin on oxidative stress biomarkers and adipokines in army cadets: a placebo-controlled, double-blind study

Original Contribution

Dietary magnesium intake and the risk of diabetes in the Japanese community: results from the Takayama study

Original Contribution

Belgian primary school children’s hydration status at school and its personal determinants

Original Contribution

Zinc enhances the number of regulatory T cells in allergen-stimulated cells from atopic subjects
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits