Reduced intestinal lipid absorption improves glucose metabolism in aged G2-Terc knockout mice.

BACKGROUND: Biological aging is an important factor leading to the development of pathologies associated with metabolic dysregulation, including type 2 diabetes, cancer, cardiovascular and neurodegenerative diseases. Telomere length, a central feature of aging, has additionally been identified as inversely associated with glucose tolerance and the development of type 2 diabetes. However, the effects of shortened telomeres on body weight and metabolism remain incompletely understood. Here, we studied the metabolic consequences of moderate telomere shortening using second generation loss of telomerase activity in mice. RESULTS: Aged male and female G2 Terc-/- mice and controls were characterized with respect to body weight and composition, glucose homeostasis, insulin sensitivity and metabolic activity. This was complemented with molecular and histological analysis of adipose tissue, liver and the intestine as well as microbiota analysis. We show that moderate telomere shortening leads to improved insulin sensitivity and glucose tolerance in aged male and female G2 Terc-/- mice. This is accompanied by reduced fat and lean mass in both sexes. Mechanistically, the metabolic improvement results from reduced dietary lipid uptake in the intestine, characterized by reduced gene expression of fatty acid transporters in enterocytes of the small intestine. Furthermore, G2-Terc-/- mice showed significant alterations in the composition of gut microbiota, potentially contributing to the improved glucose metabolism. CONCLUSIONS: Our study shows that moderate telomere shortening reduces intestinal lipid absorption, resulting in reduced adiposity and improved glucose metabolism in aged mice. These findings will guide future murine and human aging studies and provide important insights into the age associated development of type 2 diabetes and metabolic syndrome.

L-Serine Supplementation Blunts Fasting-Induced Weight Regain by Increasing Brown Fat Thermogenesis.

Weight regain after fasting, often exceeding the pre-fasting weight, is a common phenomenon and big problem for the treatment of obesity. Thus, novel interventions maintaining reduced body weight are critically important to prevent metabolic disease. Here we investigate the metabolic effects of dietary L-serine supplementation, known to modulate various organ functions. C57BL/6N-Rj male mice were supplemented with or without 1% L-serine in their drinking water and fed with a chow or high-fat diet. Mice were fed either ad libitum or subjected to repeated overnight fasting. Body weight, body composition, glucose tolerance and energy metabolism were assessed. This was combined with a detailed analysis of the liver and adipose tissues, including the use of primary brown adipocytes to study mitochondrial respiration and protein expression. We find that L-serine supplementation has little impact on systemic metabolism in ad libitum-fed mice. Conversely, L-serine supplementation blunted fasting-induced body weight regain, especially in diet-induced obese mice. This reduction in body weight regain is likely due to the increased energy expenditure, based on elevated brown adipose tissue activity. Thus, L-serine supplementation during and after weight-loss could reduce weight regain and thereby help tackle one of the major problems of current obesity therapies.

Ex vivo toxicological evaluation of experimental anticancer gold(i) complexes with lansoprazole-type ligands.

Gold-based compounds are of great interest in the field of medicinal chemistry as novel therapeutic (anticancer) agents due to their peculiar reactivity and mechanisms of action with respect to organic drugs. Despite their promising pharmacological properties, the possible toxic effects of gold compounds need to be carefully evaluated in order to optimize their design and applicability. This study reports on the potential toxicity of three experimental gold-based anticancer compounds featuring lansoprazole ligands (1-3) studied in an ex vivo model, using rat precision cut kidney and liver slices (PCKS and PCLS, respectively). The results showed a different toxicity profile for the tested compounds, with the neutral complex 2 being the least toxic, even less toxic than cisplatin, followed by the cationic complex 1. The dinuclear cationic gold complex 3 was the most toxic in both liver and kidney slices. This result correlated with the metal uptake of the different compounds assessed by ICP-MS, where complex 3 showed the highest accumulation of gold in liver and kidney slices. Interestingly compound 1 showed the highest selectivity towards cancer cells compared to the healthy tissues. Histomorphology evaluation showed a similar pattern for all three Au(i) complexes, where the distal tubular cells suffered the most extensive damage, in contrast to the damage in the proximal tubules induced by cisplatin. The binding of representative gold compounds with the model ubiquitin was also studied by ESI-MS, showing that after 24 h incubation only 'naked' Au ions were bound to the protein following ligands' loss. The mRNA expression of stress response genes appeared to be similar for both evaluated organs, suggesting oxidative stress as the possible mechanism of toxicity. The obtained results open new perspectives towards the design and testing of bifunctional gold complexes with chemotherapeutic applications.

[Characterization of anemia in children under five years of age from urban areas of Huancavelica and Ucayali, Peru]. / Caracterización de la anemia en niños menores de cinco años de zonas urbanas de Huancavelica y Ucayali en el Perú.

OBJECTIVES: Characterize anemia in children aged between 12 and 59 months from urban areas in the provinces of Coronel Portillo and Huancavelica in Peru. MATERIALS AND METHODS: Cross-sectional study carried out in two stages: a) population-based study to identify children with anemia using multistage probability sampling, and b) characterization of the serum levels of ferritin, vitamin B12, intraerythrocytic folic acid and presence of parasitosis in children with anemia. For the statistical analysis, expansion factors calculated from the sampling plan were applied. RESULTS: The prevalence of anemia was 55.9% in Huancavelica and 36.2% in Coronel Portillo. In Huancavelica, the coexistence of anemia with iron deficiency was 22.8% and anemia with vitamin B12 deficiency was 11%. In Coronel Portillo, the coexistence of anemia with iron deficiency and vitamin B12 deficiency was 15.2% and 29.7%, respectively. The most common types of anemia in Huancavelica were anemia with concurrent parasitosis (50.9%), iron deficiency anemia and parasitosis (12.3%), and iron deficiency alone (6.4%). In Coronel Portillo, it was anemia and parasitosis (54.4%), vitamin B12 deficiency and parasitosis (18.4%), and iron deficiency anemia and parasitosis (6.3%). CONCLUSIONS: The prevalence of anemia is higher than the national average, with anemia concurrent with parasitosis and anemia concurrent with two or more causes as the most common type. Consideration should be given to different causes other than iron deficiency in the programs of anemia contol for Peruvian children.

Caracterización de la anemia en niños menores de cinco años de zonas urbanas de Huancavelica y Ucayali en el Perú / Characterization of anemia in children under five years of age from urban areas of Huancavelica and Ucayali, Peru

Caracterizar la anemia en niños entre 12 a 59 meses pertenecientes a de zonas urbanas de las provincias de Huancavelica y Coronel Portillo en el Perú. Materiales y métodos. Estudio transversal desarrollado en dos etapas: a) estudio de base poblacional para la identificación de niños con anemia mediante un muestreo probabilístico multietápico, y b) caracterización de los niveles séricos de ferritina, vitamina B12, ácido fólico intraeritrocitario y presencia de parasitosis en los niños con anemia. Para el análisis estadístico se aplicaron los factores de expansión calculados a partir del plan de muestreo. Resultados. La prevalencia de anemia en Huancavelica fue 55,9% y en Coronel Portillo 36,2%. En Huancavelica la coexistencia de anemia con deficiencia de hierro fue del 22,8% y de anemia con deficiencia de vitamina B12 del 11%, en Coronel Portillo la coexistencia de anemia con deficiencia de hierro y déficit de vitamina B12 fueron del 15,2 y 29,7% respectivamente. Los tipos de anemia más frecuentes en Huancavelica fueron anemia concurrente con parasitosis (50,9%); anemia ferropénica y parasitosis (12,3%), y solo ferropénica (6,4%); en Coronel Portillo fue anemia y parasitosis (54,4%); deficiencia de vitamina B12 y parasitosis (18,4%) y anemia ferropénica y parasitosis (6,3%). Conclusiones. La prevalencia de anemia es superior al promedio nacional, siendo la anemia concurrente con parasitosis y la anemia concurrente con dos o más causas el tipo más frecuente. Se debe considerar etiologías diferentes a la deficiencia de hierro en los programas de control de la anemia en niños peruanos...

Characterize anemia in children aged between 12 and 59 months from urban areas in the provinces of Coronel Portillo and Huancavelica in Peru. Materials and methods. Cross-sectional study carried out in two stages: a) population-based study to identify children with anemia using multistage probability sampling, and b) characterization of the serum levels of ferritin, vitamin B12, intraerythrocytic folic acid and presence of parasitosis in children with anemia. For the statistical analysis, expansion factors calculated from the sampling plan were applied. Results. The prevalence of anemia was 55.9% in Huancavelica and 36.2% in Coronel Portillo. In Huancavelica, the coexistence of anemia with iron deficiency was 22.8% and anemia with vitamin B12 deficiency was 11%. In Coronel Portillo, the coexistence of anemia with iron deficiency and vitamin B12 deficiency was 15.2% and 29.7%, respectively. The most common types of anemia in Huancavelica were anemia with concurrent parasitosis (50.9%), iron deficiency anemia and parasitosis (12.3%), and iron deficiency alone (6.4%). In Coronel Portillo, it was anemia and parasitosis (54.4%), vitamin B12 deficiency and parasitosis (18.4%), and iron deficiency anemia and parasitosis (6.3%). Conclusions. The prevalence of anemia is higher than the national average, with anemia concurrent with parasitosis and anemia concurrent with two or more causes as the most common type. Consideration should be given to different causes other than iron deficiency in the programs of anemia contol for Peruvian children...

[Consumption of chispitas® multimicronutrient supplements and anemia in 6 - 35-month-old children: cross-cut study in the context of a populational health intervention in Apurimac, Peru]. / Consumo de suplementos con multimicronutrientes Chispitas® y anemia en niños de 6 a 35 meses: estudio transversal en el contexto de una intervención poblacional en Apurímac, Perú

OBJECTIVES: To assess the implementation of the Universal "Chispitas®" Multimicronutrient Supplement Program in Apurimac by determining the quantity and quality of sachets consumed and their connection with anemia, in 6 - 35-month-old children. MATERIALS AND METHODS: A crosscut study was conducted by using a multistage sample in 2010. Anemia was considered to be related to altitude-adjusted hemoglobin values below 110 g/L. The consumption of multimicronutrients was classified as follows: less than 30; 30 to 59, and 60 or more sachets. The quality of consumption was considered to be adequate when the mother indicated that the child ate all his food with the supplement. The rationale for prevalence (RPa) adjusted by Poisson regression was calculated. RESULTS: 714 participants were included, 25.3% of which lived in poor houses and 59.2% in extreme poverty; 52.6% lived at over 3000 m of altitude. The prevalence of anemia was 51.3% (CI95%: 47.1-55.4%), 5.4% did not receive intervention; 60.3% consumed 60 or more sachets and 49.0% consumed them adequately. No association between the number of sachets received or consumed and anemia (p<0.05) was found. Children who consumed the supplement adequately showed lower prevalence of anemia than those who did not (RPa: 0.81; CI95%: 0.68-0.96) CONCLUSIONS: In order to reduce the prevalence of anemia, attention should not only focus on giving or consuming the necessary quantity of multimicronutrients, but also on ensuring that the consumption process is adequate, and work needs to be done in this area in order to improve this intervention.

Consumo de suplementos con multimicronutrientes Chispitas® y anemia en niños de 6 a 35 meses: estudio transversal en el contexto de una intervención poblacional en Apurímac, Perú / Consumption of chispitas® multimicronutrient supplements and anemia in 6 - 35-month-old children: cross-cut study in the context of a populational health intervention in Apurimac, Peru

Objetivos. Evaluar la implementación del programa de suplementación universal con multimicronutrientes “Chispitas®” en la región Apurímac a través de la cantidad y calidad de sobres consumidos y su relación con la anemia, en niños de 6 a 35 meses. Materiales y métodos. Se realizó un estudio transversal usando un muestreo multietápico en el 2010. Se consideró como anemia a los valores de hemoglobina ajustados por altitud menores de 110 g/L. El consumo de multimicronutrientes se categorizó en: menor de 30; de 30 a 59, y 60 o más sobres. La calidad del consumo fue adecuada cuando la madre refería que el niño consumía toda la comida con el suplemento. Se calculó las razones de prevalencia (RPa) ajustadas por regresión de Poisson. Resultados. Se incluyó 714 participantes, 25,3% vivía en hogares pobres y 59,2% en extrema pobreza; 52,6% residía a más de 3000 m de altitud. La prevalencia de anemia fue de 51,3% (IC95%: 47,1-55,4%), 5,4% no recibió la intervención; 60,3% consumió 60 o más sobres y 49,0% los consumió en forma adecuada. No se encontró asociación entre la cantidad de sobres recibidos o consumidos y la anemia (p<0,05). Aquellos niños que consumieron el suplemento en forma adecuada tuvieron menor prevalencia de anemia que aquellos que no lo hicieron (RPa: 0,81; IC95%: 0,68-0,96) Conclusiones. No basta con entregar o consumir la cantidad necesaria de los multimicronutrientes, sino asegurar que el proceso de consumo sea adecuado para lograr una reducción de la prevalencia de anemia, aspecto que debe ser trabajado para mejorar esta intervención.

Objectives. To assess the implementation of the Universal “Chispitas®” Multimicronutrient Supplement Program in Apurimac by determining the quantity and quality of sachets consumed and their connection with anemia, in 6 - 35-month-old children. Materials and methods. A crosscut study was conducted by using a multistage sample in 2010. Anemia was considered to be related to altitude-adjusted hemoglobin values below 110 g/L. The consumption of multimicronutrients was classified as follows: less than 30; 30 to 59, and 60 or more sachets. The quality of consumption was considered to be adequate when the mother indicated that the child ate all his food with the supplement. The rationale for prevalence (RPa) adjusted by Poisson regression was calculated. Results. 714 participants were included, 25.3% of which lived in poor houses and 59.2% in extreme poverty; 52.6% lived at over 3000 m of altitude. The prevalence of anemia was 51.3% (CI95%: 47.1-55.4%), 5.4% did not receive intervention; 60.3% consumed 60 or more sachets and 49.0% consumed them adequately. No association between the number of sachets received or consumed and anemia (p<0.05) was found. Children who consumed the supplement adequately showed lower prevalence of anemia than those who did not (RPa: 0.81; CI95%: 0.68-0.96) Conclusions. In order to reduce the prevalence of anemia, attention should not only focus on giving or consuming the necessary quantity of multimicronutrients, but also on ensuring that the consumption process is adequate, and work needs to be done in this area in order to improve this intervention.