1 3 Eur J Nutr DOI 10.1007/s00394-015-1115-7 ORIGINAL CONTRIBUTION Methylation patterns of Vegfb promoter are associated with gene and protein expression levels: the effects of dietary fatty acids Roberto Monastero 1,2 · Sara García‑Serrano 1,2 · Ana Lago‑Sampedro 1,2 · Francisca Rodríguez‑Pacheco 1,2 · Natalia Colomo 1,2 · Sonsoles Morcillo 4,5 · Gracia M. Martín‑Nuñez 1,2 · Juan M. Gomez‑Zumaquero 3 · Eduardo García‑Fuentes 1,4 · Federico Soriguer 1,2 · Gemma Rojo‑Martínez 1,2 · Eva García‑Escobar 1,2 Received: 30 March 2015 / Accepted: 22 November 2015 © Springer-Verlag Berlin Heidelberg 2015 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 medi- ated, 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. Keywords Adipose tissue · Dietary fatty acids · Gene expression · Nutriepigenetic regulation · Vegfb Introduction Whole-body lipid homeostasis requires a fine tuning of fatty acid transport and utilization by metabolically active tissues. In the last few years, most attention has been given to examining a possible role for fatty acid transporters in insulin resistance, obesity and type 2 diabetes because these are associated with marked changes in lipid metabolism, including increased plasma fatty acid concentrations [1, 2] and increased intramuscular triacylglycerol depots [3] among others; because of all these factors, the transmem- brane fatty acid transport system and its regulation factors have been considered a key point in the study of metabolic diseases development. In addition to the traditional fatty acid transport proteins (FATPs), the implication of the 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, mon- ounsaturated 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 Gemma Rojo-Martínez and Eva García-Escobar have contributed equally to this work. Gemma Rojo-Martínez and Eva García- Escobar are joint senior authors. Electronic supplementary material The online version of this article (doi:10.1007/s00394-015-1115-7) contains supplementary material, which is available to authorized users. * Sara García-Serrano garciasara79@hotmail.com * Eva García-Escobar eyring@gmail.com 1 UGC Endocrinología y Nutrición, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Universitario Regional de Málaga, Málaga, Spain 2 CIBER de Diabetes y Enfermedades Metabólicas asociadas (CIBERDEM CB07/08/0019), Instituto de Salud Carlos III, Málaga, Spain 3 ECAI de Genomica del Instituto de Investigación Biomédica de Málaga (IBIMA), Málaga, Spain 4 CIBER de Obesidad y Nutrición (CIBEROBN CB06/03/0018), Instituto de Salud Carlos III, Málaga, Spain 5 UGC Endocrinología y Nutrición, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Universitario Virgen de la Victoria, Málaga, Spain