Dietary regulation of VEGFb gene expression is related to its promoter DNA methylation levels

Motivación: Recientemente se ha descrito la implicación del factor de crecimiento del endotelio vascular B (VEGFb) en la absorción de los ácidos grasos (AGs) en los tejidos y su relación con el desarrollo de diferentes enfermedades metabólicas tal como la obesidad y la diabetes tipo 2. El objetivo de este estudio es investigar el efecto de la composición de los AGs de la dieta en la regulación de la expresión génica del VEGFb en los tejidos adiposos de rata, y si este efecto está relacionado mediante modificación por metilación del DNA en el promotor del VEGFb. De esta forma la modificación de la dieta puede ser una nueva estrategia para modular la acumulación patológica de los lípidos en la obesidad o en la diabetes. Métodos: A cada grupo de ratas fue asignado una de tres diferentes dietas isoenergéticas, cada una con una concentración diferente de AGs saturados, mono y poliinsaturados (dieta de aceite de coco, aceite de oliva y de girasol). Los animales fueron alimentados durante un mes. Las muestras de tejido adiposo visceral (VAT) y subcutáneo (SAT) se tomaron inmediatamente para estudios de metilación y  expresión génica. También de estos tejidos se tomaron mediciones de la composición de los AGs de los triglicéridos y la acumulación total de los tejidos adiposos. Resultados: Ni los pesos de los animales ni de los depósitos adiposos ni la acumulación lípidica del tejido cambiaban con las dietas. La composición en AGs de ambos tejidos fue significativamente diferente en función de la dieta consumida(p <0,0001 para todos los AGs estudiados). El nivel de expresión del gen VEGFb se correlaciona directamente con la acumulación de lípidos de cada tejido y con la composición de AGs del tejido. En ambos tejidos, los niveles de expresión génica del VEGFb y de metilación del promotor fueron diferentes con respecto a la dieta consumida, estando la expresión génica y los niveles de metilación del promotor del VEGFb inversamente correlacionados. Los valores más altos de expresión génica, y los más bajos de metilación del promotor, se encontraron en las ratas alimentadas con la dieta rica en aceite de coco. Conclusiones: La expresión del gen Vegfb en el tejido adiposo se asocia con el aumento en la acumulación de grasa. El estudio presentado muestra que la expresión génica del Vegfb está regulada por los AGs de la dieta, y esta regulación está relacionada con el nivel de metilación de la región promotora del Vegfb

Reflexiones sobre la brucelosis de la oveja

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<i>H. pylori</i> Eradication Treatment Alters Gut Microbiota and GLP-1 Secretion in Humans

Changes in the intestinal microbial community and some metabolic disturbances, including obesity and type2 diabetes, are related. Glucagon-like peptide-1 (GLP-1) regulates glucose homeostasis. Microbiota have been linked to incretin secretion. Antibiotic use causes changes in microbial diversity and composition. Our aim was to evaluate the relationship between microbiota changes and GLP-1 secretion. A prospective case-control study with a Helicobacter pylori-positive patient model involving subjects under eradication therapy (omeprazole, clarithromycin, and amoxicillin). Forty patients with H. pylori infection and 20 matched participants, but negative for H. pylori antigen. Patients were evaluated before and two months after treatment. We analyzed anthropometric measurements, carbohydrate metabolism, lipid profile, and C-reactive protein. Gut microbiota composition was analyzed through 16S rRNA amplicon sequencing (IlluminaMiSeq). Eradication treatment for H. pylori decreased bacterial richness (Chao1, p = 0.041). Changes in gut microbiota profiles were observed at phylum, family, genus and species levels. GLP-1 secretion and variables of carbohydrate metabolism were improved. Correlations were seen between GLP-1 changes and variations within microbial community abundances, specifically Bifidobacterium adolescentis, the Lachnobacterium genus, and Coriobacteriaceae family. A conventional treatment to eradicate H. pylori could improve carbohydrate metabolism possibly in relation with an increase in GLP-1 secretion. GLP-1 secretion may be related to alterations in intestinal microbiota, specifically Lachnobacterium, B. adolescentis and Coriobacteriaceae

GRK2 levels in myeloid cells modulate adipose-liver crosstalk in high fat diet-induced obesity

Macrophages are key effector cells in obesity-associated inflammation. G protein-coupled receptor kinase 2 (GRK2) is highly expressed in different immune cell types. Using LysM-GRK2+/− mice, we uncover that a reduction of GRK2 levels in myeloid cells prevents the development of glucose intolerance and hyperglycemia after a high fat diet (HFD) through modulation of the macrophage pro-inflammatory profile. Low levels of myeloid GRK2 confer protection against hepatic insulin resistance, steatosis and inflammation. In adipose tissue, pro-inflammatory cytokines are reduced and insulin signaling is preserved. Macrophages from LysM-GRK2+/− mice secrete less pro-inflammatory cytokines when stimulated with lipopolysaccharide (LPS) and their conditioned media has a reduced pathological influence in cultured adipocytes or naïve bone marrow-derived macrophages. Our data indicate that reducing GRK2 levels in myeloid cells, by attenuating pro-inflammatory features of macrophages, has a relevant impact in adipose-liver crosstalk, thus preventing high fat diet-induced metabolic alterations.We acknowledge support by Ministerio de Economía y Competitividad (MINECO/FEDER), Spain (grant SAF2017-84125-R to FM and CM and SAF2017-82436R to LB); CIBER de Enfermedades Cardiovasculares (CIBERCV). Instituto de Salud Carlos III, Spain (grant CB16/11/00278 to F.M., CB16/11/00222 to L.B., and, PI15/01114 to Francisco Tinaones (Universidad De Málaga, Spain), co-funded with European FEDER contribution); European Foundation for the Study of Diabetes (EFSD) Novo Nordisk Partnership for Diabetes Research in Europe Grant (to F.M.); and Programa de Actividades en Biomedicina de la Comunidad de Madrid-B2017/BMD-3671-INFLAMUNE to FM and MF.. I.M.-I. was supported by the “MS type I” program (CP16/00163). The authors thank the Metagenomic Platform of the Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y la Nutrición, CIBERobn, Instituto de Salud Carlos III (ISCIII), Spain. We appreciate the help of the CBMSO Facilities, in particular Flow Cytometry, Genomics and Animal Care. We acknowledge Paula Ramos for technical support. We also acknowledge the institutional support to the CBMSO from Fundación Ramón Areces.Peer reviewe

Iodine status and thyroid function among Spanish schoolchildren aged 6-7 years: the Tirokid study.

I deficiency is still a worldwide public health problem, with children being especially vulnerable. No nationwide study had been conducted to assess the I status of Spanish children, and thus an observational, multicentre and cross-sectional study was conducted in Spain to assess the I status and thyroid function in schoolchildren aged 6-7 years. The median urinary I (UI) and thyroid-stimulating hormone (TSH) levels in whole blood were used to assess the I status and thyroid function, respectively. A FFQ was used to determine the consumption of I-rich foods. A total of 1981 schoolchildren (52 % male) were included. The median UI was 173 μg/l, and 17·9 % of children showed UI<100 μg/l. The median UI was higher in males (180·8 v. 153·6 μg/l; P<0·001). Iodised salt (IS) intake at home was 69·8 %. IS consumption and intakes of ≥2 glasses of milk or 1 cup of yogurt/d were associated with significantly higher median UI. Median TSH was 0·90 mU/l and was higher in females (0·98 v. 0·83; P<0·001). In total, 0·5 % of children had known hypothyroidism (derived from the questionnaire) and 7·6 % had TSH levels above reference values. Median TSH was higher in schoolchildren with family history of hypothyroidism. I intake was adequate in Spanish schoolchildren. However, no correlation was found between TSH and median UI in any geographical area. The prevalence of TSH above reference values was high and its association with thyroid autoimmunity should be determined. Further assessment of thyroid autoimmunity in Spanish schoolchildren is desirable.The study was funded by Merck-SeronoYe