Dietary animal and plant protein intakes and their associations with obesity and cardio-metabolic indicators in European adolescents: The HELENA cross-sectional study

Background: Previous studies suggest that dietary protein might play a beneficial role in combating obesity and its related chronic diseases. Total, animal and plant protein intakes and their associations with anthropometry and serum biomarkers in European adolescents using one standardised methodology across European countries are not well documented. Objectives: To evaluate total, animal and plant protein intakes in European adolescents stratified by gender and age, and to investigate their associations with cardio-metabolic indicators (anthropometry and biomarkers). Methods: The current analysis included 1804 randomly selected adolescents participating in the HELENA study (conducted in 2006-2007) aged 12.5-17.5 y (47% males) who completed two non-consecutive computerised 24-h dietary recalls. Associations between animal and plant protein intakes, and anthropometry and serum biomarkers were examined with General linear Model multivariate analysis. Results: Average total protein intake exceeded the recommendations of World Health Organization and European Food Safety Authority. Mean total protein intake was 96 g/d (59% derived from animal protein). Total, animal and plant protein intakes (g/d) were significantly lower in females than in males and total and plant protein intakes were lower in younger participants (12.5-14.9 y). Protein intake was significantly lower in underweight subjects and higher in obese ones; the direction of the relationship was reversed after adjustments for body weight (g/(kg.d)). The inverse association of plant protein intakes was stronger with BMI z-score and body fat percentage (BF%) compared to animal protein intakes. Additionally, BMI and BF% were positively associated with energy percentage of animal protein. Conclusions: This sample of European adolescents appeared to have adequate total protein intake. Our findings suggest that plant protein intakes may play a role in preventing obesity among European adolescents. Further longitudinal studies are needed to investigate the potential beneficial effects observed in this study in the prevention of obesity and related chronic diseases

The Beaker phenomenon and the genomic transformation of northwest Europe

From around 2750 to 2500 bc, Bell Beaker pottery became widespread across western and central Europe, before it disappeared between 2200 and 1800 bc. The forces that propelled its expansion are a matter of long-standing debate, and there is support for both cultural diffusion and migration having a role in this process. Here we present genome-wide data from 400 Neolithic, Copper Age and Bronze Age Europeans, including 226 individuals associated with Beaker-complex artefacts. We detected limited genetic affinity between Beaker-complex-associated individuals from Iberia and central Europe, and thus exclude migration as an important mechanism of spread between these two regions. However, migration had a key role in the further dissemination of the Beaker complex. We document this phenomenon most clearly in Britain, where the spread of the Beaker complex introduced high levels of steppe-related ancestry and was associated with the replacement of approximately 90% of Britain’s gene pool within a few hundred years, continuing the east-to-west expansion that had brought steppe-related ancestry into central and northern Europe over the previous centuries

Cardiotrophin-1 (CT-1) plays a key role in enhancing antiapoptotic defenses and maintaining mitochondrial function during liver regeneration

Resumen del póster presentado a The International Liver Congress – 48th Annual meeting of the European Association for the Study of the Liver celebrado en Paises Bajos en abril de 2013.-- et al.[Background and Aims]: Following partial hepatectomy (PH) the liver exhibits increased resistance against hepatocellular damaging agents but the mechanisms remain poorly characterised. Here, we evaluated the role of endogenous CT-1 (a potent cytoprotective cytokine) in the defence of the regenerating liver against proapoptotic insults. Since mitochondria participate in the process of cell death, we analyzed mitochondrial function in CT-1 null mice and wild type (wt) controls post-PH. [Results]: We detected increased CT-1 protein levels in serum and liver 24h after PH. At this time point serum AST and bilirubin levels were higher in CT-1 KO than in wt. We observed that Stat3 was activated 1h post-PH in wt but not in CT-1 null mice and that the anti-apoptotic gene IGFB1 was upregulated 3h post-PH at significantly higher levels in wt than in CT-1 KO. A significant elevation of the cytoprotective molecule sphingosine-1 phosphate (S1P) was found at 5 h post-PH in wt but not in CT-1 null mice. Also, sphingosine kinase 1 (SPHK1) was upregulated at 3h post-PH in wt and significantly less in CT-1 KO. In wt mice the administration of Jo2 caused less necroapoptosis in PH mice than in sham animals. However the opposite was observed in CT-1 null mice. These animals showed impaired regenarative response, compared to wt, when Jo2 was given 24h after PH. Moreover, in CT-1 KO mice mitochondrial function was impaired following PH more markedly than in wt mice and this alteration was aggravated after Jo2 challenge. [Conclusions]: During liver regeneration CT-1 is essential for upgrading antiapoptotic defences and maintaining mitochondrial function. CT-1 appears to be crucial for regeneration of damaged livers.Peer Reviewe

Overexpression of 2-oxoglutaratecarrier in hepatocellular carcinoma overcomes cholesterol-mediated mitochondrial GSH depletion to evade cell death and promote in vivo tumor growth

Trabajo presentado al 46th Annual Meeting of the European Association for the Study of the Liver (EASL) celebrado en Berlín del 30 de marzo al 3 de abril de 2011.Mitochondrial cholesterol is emerging as a critical player in liver pathobiology. While mitochondrial cholesterol contributes to the transition from steatosis to steatohepatitis through sensitization to TNF/Fas via mitochondrial GSH (mGSH) depletion, hepatocellular carcinoma (HCC) cells exhibit increased mitochondrial cholesterol loading which is paradoxically associated with unimpaired GSH transport in mitochondria and hence undepleted mGSH levels. Since the 2-oxoglutarate carrier (SLC25A11, OG) has been shown to contribute to the transport of GSH into hepatic mitochondria, our aim was to analyze the expression of OG in HCC and its impact in hypoxia susceptibility. [Methods]: OG expression was determined in HCC cell lines and in samples from patients with HCC. HepG2 and H35 cells were transfected for 48 h with the OG siRNA or the control siRNA, examining GSH levels by recycling method. HepG2 and H35 cells with or without OG mRNA silencing were cultured under hypoxic (2% O2) or normoxic (21% O2) conditions for 48 h, analyzing ROS generation, cardiolipin peroxidation and cell viability. Moreover, we generated a Hep3B clone with stable downregulation of OG (Hep3B-OG) carrier to determine in vivo tumor growth. [Results]: While cholesterol loading in rat or mice hepatic mitochondria impairs GSH transport leading to mGSH depletion, mitochondria from HepG2, Hep3B or H35 cells exhibit unrestricted GSH transport despite increased cholesterol loading and decreased membrane fluidity. Interestingly, both HepG2 and H35 cells as well as samples from patients with HCC display enhanced OG mRNA and protein expression compared to rat liver or human hepatic extracts. Moreover, OG silencing by siRNA led to mGSH depletion (50–60%), sensitizing HCC cells to hypoxia-induced ROS generation, cardiolipin peroxidation, cytochrome c release and apoptosis. These findings were reproduced by pharmacological depletion of mGSH by BSO, which potentiated hypoxia-induced cardiolipin peroxidation and cell death. Finally, the rate of tumor growth in vivo of Hep3B-OG clones was lower compared to Hep3B cells, which was accompanied by increased TUNEL staining of corresponding tumors. [Conclusions]: OG overexpression is a novel strategy of HCC to resist and adapt to hypoxia, and its silencing sensitizes them to hypoxia by depleting mGSH levels.Peer Reviewe