Angiogenin mediates paternal inflammation-induced metabolic disorders in offspring through sperm tsRNAs.

Paternal environmental inputs can influence various phenotypes in offspring, presenting tremendous implications for basic biology and public health and policy. However, which signals function as a nexus to transmit paternal environmental inputs to offspring remains unclear. Here we show that offspring of fathers with inflammation exhibit metabolic disorders including glucose intolerance and obesity. Deletion of a mouse tRNA RNase, Angiogenin (Ang), abolished paternal inflammation-induced metabolic disorders in offspring. Additionally, Ang deletion prevented the inflammation-induced alteration of 5'-tRNA-derived small RNAs (5'-tsRNAs) expression profile in sperm, which might be essential in composing a sperm RNA 'coding signature' that is needed for paternal epigenetic memory. Microinjection of sperm 30-40 nt RNA fractions (predominantly 5'-tsRNAs) from inflammatory Ang+/+ males but not Ang-/- males resulted in metabolic disorders in the resultant offspring. Moreover, zygotic injection with synthetic 5'-tsRNAs which increased in inflammatory mouse sperm and decreased by Ang deletion partially resembled paternal inflammation-induced metabolic disorders in offspring. Together, our findings demonstrate that Ang-mediated biogenesis of 5'-tsRNAs in sperm contributes to paternal inflammation-induced metabolic disorders in offspring.

Metabolic syndrome in children.

Despite plenty of currently available information on metabolic syndrome (MetS) in children and adolescents, there are still uncertainties regarding definition, prevention, management and treatment of MetS in children. The first approach to MetS in children consists of lifestyle interventions (nutritional education, physical activity). These recommendations are often difficult to achieve, especially for adolescents, therefore, there is usually a lack of successful outcomes. A pharmacological intervention in obese children may be needed in some cases, with the aim to improve the effects of these primary prevention interventions. Metformin seems to be safe and presents evident positive effects on insulin sensitivity, but long-term and consistent data are still missing to establish its role in the pediatric population and the possible effectiveness of other emergent treatments such as glucagon-like peptide-1 analogues, dipeptidylpeptidase-4 inhibitors, dual inhibitors of SGLT1 and SGLT2 and weight loss drugs. Bariatric surgery might be helpful in selected cases. The aim of this review is to present the most recent available treatments for the main components of metabolic syndrome, with a focus on insulin resistance. A short mention of management of congenital forms of insulin resistance will be included too.

Heritability of the Severity of the Metabolic Syndrome in Whites and Blacks in 3 Large Cohorts.

BACKGROUND: Although dichotomous criteria for the metabolic syndrome (MetS) appear heritable, it is not known whether MetS severity as assessed by a continuous MetS score is heritable and whether this varies by race. METHODS AND RESULTS: We used SOLAR (Sequential Oligogenic Linkage Analysis Routines) to evaluate heritability of Adult Treatment Panel-III MetS and a sex- and race-specific MetS severity Z score among 3 large familial cohorts: the JHS (Jackson Heart Study, 1404 black participants), TOPS (Take Off Pounds Sensibly, 1947 white participants), and PLRS (Princeton Lipid Research Study, 229 black and 527 white participants). Heritability estimates were larger for Adult Treatment Panel-III MetS among black compared with white cohort members (JHS 0.48; 95% confidence interval [CI], 0.28-0.68 and PLRS blacks 0.93 [95% CI, 0.73-1.13] versus TOPS 0.21 [95% CI, -0.18 to 0.60] and PLRS whites 0.27 [95% CI, -0.04 to 0.58]). The difference by race narrowed when assessing heritability of the MetS severity score (JHS 0.52 [95% CI, 0.38, 0.66] and PLRS blacks 0.64 [95% CI, 0.13-1.15] versus TOPS 0.23 [95% CI, 0.15-0.31] and PLRS whites 0.60 [95% CI, 0.33-0.87]). There was a high degree of genetic and phenotypic correlation between MetS severity and the individual components of MetS among all groups, although the genetic correlations failed to reach statistical significance among PLRS blacks. Meta-analyses revealed a combined heritability estimate for Adult Treatment Panel-III MetS of 0.24 (95% CI, 0.11-0.36) and for the MetS severity score of 0.50 (95% CI, -0.05 to 0.99). CONCLUSIONS: MetS severity seems highly heritable among whites and blacks. This continuous MetS severity Z score may provide a more useful means of characterizing phenotypic MetS in genetic studies by minimizing racial differences.

Maternal taurine supplementation attenuates maternal fructose-induced metabolic and inflammatory dysregulation and partially reverses adverse metabolic programming in offspring.

Excessive fructose consumption is associated with insulin resistance (IR) and nonalcoholic fatty liver disease (NAFLD), and high fructose intake during pregnancy can lead to compromised fetal development in the rat. Evidence suggests that the amino acid taurine can ameliorate fructose-induced IR and NAFLD in nonpregnant animals. This study investigated the efficacy of taurine supplementation on maternal fructose-induced metabolic dysfunction and neonatal health. Time-mated Wistar rats were randomized to four groups during pregnancy and lactation: (a) control diet (CON), (b) CON supplemented with 1.5% taurine in drinking water (CT), (c) CON supplemented with fructose solution (F) and (d) F supplemented with taurine (FT). Maternal and neonatal weights, plasma cytokines and hepatic gene expression were analyzed. Maternal hyperinsulinemia, increased homeostasis model assessment of IR indices and elevated proinflammatory cytokines were observed in F group and normalized in FT group. Maternal fructose-induced hepatic steatosis accompanied with increased liver weight was ameliorated with taurine supplementation. Maternal hepatic sterol regulatory element-binding protein-1c and fatty acid synthase expression was significantly increased in the F group compared to the CON, CT and FT groups. Neonatal hepatic phosphoenolpyruvate carboxykinase expression was increased in male F neonates compared to the CON, CT and FT groups and was increased in female F and FT neonates compared to CON and CT. Interleukin-1ß expression was decreased in male CT and FT neonates compared to other male groups. Hepatic tumour necrosis factor receptor-1 was lower in the male FT group than the F group. These results demonstrate that maternal taurine supplementation can partially reverse fructose-induced maternal metabolic dysfunction and may ameliorate adverse developmental programming effects in offspring in a sex-specific manner.

A maternal mouse diet with moderately high-fat levels does not lead to maternal obesity but causes mesenteric adipose tissue dysfunction in male offspring.

The impact of an increase in maternal fat consumption on fetal metabolic programming separately from maternal obesity remains unclear. The purpose of this study was to document the effect of in utero high-fat diet exposure on the development of metabolic syndrome characteristics in offspring. C57BL/6 female mice were fed either a control diet (10% fat) or a moderately high-fat (MHF) diet (45% fat) until delivery. All pups were fostered to mothers fed with the control diet. Pups were raised on the control diet and assessed until 35 weeks of age. The caloric intake from fat was significantly increased in the MHF dams compared with the control dams. There were no significant differences in the maternal weight at mating or at gestational Day 18 between the two groups. The MHF offspring did not become obese, but they developed hypertension and glucose intolerance. Moreover, the MHF offspring had significantly higher serum non-esterified fatty acid and triglyceride levels during the refeeding state following fasting as compared with the control offspring. Serum adiponectin levels were significantly lower, and the cell size of the mesenteric adipose tissue was significantly larger in the MHF offspring than in the control offspring. The mRNA levels of the proinflammatory macrophage markers in the mesenteric adipose tissue were significantly higher in the MHF offspring than those of the control offspring. These results suggest that in utero high-fat diet exposure causes hypertension and glucose intolerance resulting from mesenteric adipose tissue dysfunction in offspring, independently of maternal obesity.

La alimentación de la madre durante el embarazo condiciona el desarrollo pancreático, el estatus hormonal del feto y la concentración de biomarcadores al nacimiento de diabetes mellitus y síndrome metabólico / Maternal nutrition during pregnancy conditions the fetal pancreas development, hormonal status and diabetes mellitus and metabolic syndrome biomarkers at birth

El embarazo es una etapa de vital importancia, donde tienen lugar múltiples procesos hiperplásicos, hipertróficos, de adaptación metabólica y de preparación para la vida extrauterina. En esta revisión se analizan aspectos centrales de la nutrición durante el embarazo, tanto en la etapa embrionaria como fetal. Se exponen los cambios más importantes que tienen lugar en el páncreas fetal, con especial mención de la susceptibilidad de este órgano central en la homeostasis de la glucosa a enfrentarse a cambios nutricionales durante su desarrollo y maduración. Se comentan algunos estudios realizados en modelos animales y en la especie humana con especial mención del papel de la nutrición materna sobre la masa de células-β, la producción de insulina y otras hormonas y la sensibilidad a la insulina. Se detallan aspectos sobre las hipótesis del genotipo y fenotipo ahorrador, señalando que la hiponutrición causa adaptaciones metabólicas que permiten al futuro ser medrar en un ambiente de nutrientes y energía reducido. Se revisan algunos aspectos de la hipótesis de Barker y se indica que la adaptación metabólica que preconiza es un arma de doble filo en el mundo actual de abundancia que nos encontramos. Por último se revisan trabajos de nuestro grupo y de otros autores, en aspectos menos estudiados que relacionan la calidad de la dieta materna con alteraciones de marcadores de resistencia/sensibilidad a la insulina en el momento del parto. En especial se estudia el papel de la relación ácidos grasos saturados/hidratos de carbono y la de ácidos grasos omega-6/omega-3 en el marco de dietas inadecuadas bajo el punto de vista del índice de alimentación saludable o de la adherencia a la dieta mediterránea que condicionan en el neonato un perfil de resistencia a la insulina. La revisión incide además en que los hábitos nutricionales deben estar fuertemente instaurados ya en la etapa pregestacional para asegurar una buena alimentación desde las primeras semanas del embarazo, y asegurar un desarrollo fetal y en particular pancreático que posibilite una homeostasis adecuada de la glucosa durante el embarazo y en etapas posteriores de la vida evitando, o al menos frenando, el desarrollo y la instauración de enfermedades degenerativas asociadas con el síndrome metabólico y la diabetes tipo 2 (AU)

Pregnancy is a vital period where several hyperplasic, hypertrophic processes together with metabolic adaptation and preparation for extra-uterine life take place. Present review accounts for central aspects of nutrition throughout gestation on the embryonic and fetal periods. It is centered in the major changes occurring in fetal pancreas, with special mention to the susceptibility of this main glucose homeostasis organ to support nutritional changes during maturation and development. Studies performed in animal models as human are commented considering the role of maternal nutrition on β-cell mass size, insulin and other pancreatic hormones production, and insulin sensitivity. Details of both the thrifty genotype and phenotype hypothesis are given, indicating that hypo/subnutrition causes metabolic adaptations that permit the future body to grow and develop itself in limited environmental and energetic conditions. The Barker hypothesis is considered suggesting that this metabolic hypothesis is a double-edged sword in the actual abundance World. Lastly the review, taking into account our own research and other papers, analyses less known aspects that relate maternal diet with insulin resistance/sensitivity markers at delivery. Particularly the role of the saturated fatty acid/carbohydrate and omega-6/omega-3 ratios in the frame of maternal diet is reviewed considering the quality of those diets under the Healthy Eating Index and the Adherence to Mediterranean Diet scores and the relationship with insulin resistance profile at birth. Present review ends indicating that nutritional habits should be strongly stated before gestation in order to assure a proper nutrition since the first moment of pregnancy. This will support an adequate fetal and pancreatic growth and development, and in turn, adequate glucose homeostasis during pregnancy and later in life, slowing down or preventing from degenerative diseases related with metabolic syndrome and type 2 diabetes mellitus (AU)

Metabolic syndrome in children born small-for-gestational age / Síndrome metabólica em crianças nascidas pequenas para a idade gestacional

Being born small-for-gestational age and a rapid increase in weight during early childhood and infancy has been strongly linked with chronic diseases, including metabolic syndrome, which has been related to intrauterine life environment and linked to epigenetic fetal programming. Metabolic syndrome includes waist circumference > 90th percentile for age, sex and race, higher levels of blood pressure, triglycerides and fasting glucose, and low levels of HDL-cholesterol. Insulin resistance may be present as early as 1 year of age, and obesity and/or type 2 diabetes are more prevalent in those born SGA than those born AGA. The programming of adaptive responses in children born SGA includes an association with increased blood pressure, changes in endothelial function, arterial properties and coronary disease. Early interventions should be directed to appropriate maternal nutrition, before and during pregnancy, promotion of breast feeding, and prevention of rapid weight gain during infancy, and to promote a healthy lifestyle.

Crianças nascidas pequenas para a idade gestacional (PIG) e um rápido ganho de peso durante a primeira e segunda infâncias estão fortemente ligados à ocorrência de doenças crônicas, incluindo a síndrome metabólica, o que está relacionado ao ambiente intrauterino e a alterações epigenéticas da programação fetal. A síndrome metabólica envolve uma circunferência abdominal > ao percentil 90 para a idade, sexo e raça, níveis mais altos de pressão sanguínea, triglicérides e glicose em jejum, e níveis baixos de HDL-colesterol. A resistência à insulina pode estar presente já no primeiro ano de vida, e a obesidade e/ou o diabetes tipo 2 são mais prevalentes em crianças nascidas PIG do que naquelas nascidas AIG. A programação de respostas adaptativas em crianças nascidas PIG inclui uma associação com uma pressão sanguínea mais alta, alterações na função endotelial e propriedades arteriais, e doença coronariana. Intervenções precoces devem ser direcionadas à nutrição apropriada, antes e durante a gravidez, promoção da amamentação e prevenção de ganho rápido de peso durante a infância e promoção de um estilo de vida saudável.

Metabolic syndrome in children born small-for-gestational age.

Being born small-for-gestational age and a rapid increase in weight during early childhood and infancy has been strongly linked with chronic diseases, including metabolic syndrome, which has been related to intrauterine life environment and linked to epigenetic fetal programming. Metabolic syndrome includes waist circumference ≥ 90(th) percentile for age, sex and race, higher levels of blood pressure, triglycerides and fasting glucose, and low levels of HDL-cholesterol. Insulin resistance may be present as early as 1 year of age, and obesity and/or type 2 diabetes are more prevalent in those born SGA than those born AGA. The programming of adaptive responses in children born SGA includes an association with increased blood pressure, changes in endothelial function, arterial properties and coronary disease. Early interventions should be directed to appropriate maternal nutrition, before and during pregnancy, promotion of breast feeding, and prevention of rapid weight gain during infancy, and to promote a healthy lifestyle.

Beneficial effects of modified egg* on oxidative stress in F1- generation of metabolic syndrome-X induced Wistar rat.

Congenital malformations of neonates are one of the adverse effects of diabetic pregnancy which can be prevented by supplementation of vitamin E and C. The survived neonates usually are at higher risk to diabetes, hypertension, dyslipidemia and cardiovascular diseases that may possibly be prevented through antioxidants administration. In view of this information, the efficacy of modified poultry egg enriched with optimum minerals, vitamin E and omega-3 fatty acids was studied on F1-generation, which were made to survive by feeding them this modified egg to diabetic mothers of Wistar rats. The survived F1-generation displayed hyperglycemia, dyslipidemia and hypertension like their parents, evaluated after three months of the experiment. Their mineral status revealed a higher Zn and lower Cu, Mg and Mn levels in liver and kidney. Their lipid peroxidation products were however higher and the enzyme activities of superoxide dismutase, catalase, glutathione-S-transferase, glutathione reductase, glutathione (reduced) and glucose -6 phosphate dehydrogenase were significantly lower. In the other group of F1-generation, fed modified egg mixed diet, a significant reduction in the blood pressure, serum glucose, serum lipid profile, and the lipid peroxidation products, and a significant increase in the activities of enzymes per se with reversal of Zn, Cu, Mg and Mn levels closer to the control group were recorded. The data suggest that the modified egg can ameliorate the oxidative stress in F1-generation of diabetic rats by improving the mineral status in their body.