Metabolic Effects of CCN5/WISP2 Gene Deficiency and Transgenic Overexpression in Mice

CCN5/WISP2 is a matricellular protein, the expression of which is under the regulation of Wnt signaling and IGF-1. Our initial characterization supports the notion that CCN5 might promote the proliferation and survival of pancreatic β-cells and thus improve the metabolic profile of the animals. More recently, the roles of endogenous expression of CCN5 and its ectopic, transgenic overexpression on metabolic regulation have been revealed through two reports. Here, we attempt to compare the experimental findings from those studies, side-by-side, in order to further establish its roles in metabolic regulation. Prominent among the discoveries was that a systemic deficiency of CCN5 gene expression caused adipocyte hypertrophy, increased adipogenesis, and lipid accumulation, resulting in insulin resistance and glucose intolerance, which were further exacerbated upon high-fat diet feeding. On the other hand, the adipocyte-specific and systemic overexpression of CCN5 caused an increase in lean body mass, improved insulin sensitivity, hyperplasia of cardiomyocytes, and increased heart mass, but decreased fasting glucose levels. CCN5 is clearly a regulator of adipocyte proliferation and maturation, affecting lean/fat mass ratio and insulin sensitivity. Not all results from these models are consistent; moreover, several important aspects of CCN5 physiology are yet to be explored.

Childhood adiposity associated with expanded effector memory CD8 + and Vδ2 +Vγ9 + T cells

Context Adult obesity is associated with chronic low-grade inflammation and may give rise to future chronic disease. However, it is unclear whether adiposity-related inflammation is already apparent at young age. Objective To study associations between child’s adiposity measures with circulating monocytes and naive and memory subsets in CD4, CD8, and γδ T-cell lineages. Design, setting, participants 890 ten-year-old children from the Generation R Cohort were subjected to dual-energy X-ray absorptiometry and magnetic resonance imaging for body composition (BMI, fat mass index (FMI), android-to-gynoid fat mass ratio, visceral fat index, liver fat fraction). Main outcome measures Blood sampling for detailed immunophenotyping of leukocytes by 11-color-flow cytometry at 10 years. Results The following statistically significant associations were observed: 1SD increase in total FMI was associated with +8.4% (95%CI 2.0;15.2) Vδ2 +Vγ9 + and +7.4% (95%CI 2.4;12.5) CD8 +TEMRO cell numbers. 1SD increase in visceral fat index was associated with +10.7% (95%CI 3.3;18.7) Vδ2 +Vγ9 + and +8.3% (95%CI 2.6;14.4) CD8 +TEMRO cell numbers. Higher android-to-gynoid fat mass ratio was only associated with higher Vδ2 +Vγ9 + T cells. Liver fat was associated with higher CD8 +TEMRO cells but not with Vδ2 +Vγ9 + T cells. Only liver fat was associated with lower Th17 cell numbers: 1SD increase was associated with -8.9% (95%CI -13.7;-3.7) Th17 cells. No associations for total CD8 +, CD4 + T cells or monocytes were observed. BMI was not associated with immune cells. Conclusion Higher Vδ2 +Vγ9 + and CD8 +TEMRO cell numbers in children with higher visceral fat index could reflect that adiposity-related inflammation is present in children with adiposity of a general population.

Decreased Muscle-to-Fat Mass Ratio Is Associated with Low Muscular Fitness and High Alanine Aminotransferase in Children and Adolescent Boys in Organized Sports Clubs

Decreased muscle-to-fat mass ratio (MFR) is associated with pediatric nonalcoholic fatty liver disease (NAFLD) and may reduce muscular fitness. Regular exercise in sports clubs has not led to reductions in obesity in children and adolescents; they may have decreased MFR. Decreased MFR could cause reduced muscular fitness, which may put them at risk for NAFLD development. We investigated whether MFR is related to muscular fitness and serum alanine aminotransferase (ALT), to determine whether MFR could be used to screen for NAFLD in children and adolescent boys belonging to sports clubs. Altogether, 113 participants (aged 7–17 years) who underwent body composition, laboratory, and muscular fitness measurements during a medical checkup were divided into tertiles according to their MFR. Lower extremity muscular fitness values were significantly decreased in the lowest MFR tertile (p < 0.001); conversely, serum ALT levels were significantly increased (p < 0.01). Decreased MFR significantly increased the risk of elevated ALT, which requires screening for NAFLD, after adjusting for age, obesity, muscular fitness parameters, and metabolic risk factors (odds ratio = 8.53, 95% confidence interval = 1.60–45.6, p = 0.012). Physical fitness and body composition assessments, focusing on MFR, can be useful in improving performance and screening for NAFLD in children and adolescents exercising in sports clubs.

Birth by cesarean delivery and central adiposity in adolescents from a birth cohort

The aim of this study was to analyze the association between birth by cesarean section and central adiposity in adolescents in São Luís, Maranhão State, Brazil. This was a cohort study that included 601 participants evaluated at birth and at 18-19 years. At birth we assessed type of delivery, maternal education, family income, maternal marital status, maternal body mass index before pregnancy, prenatal care, maternal smoking habit, gestational age at delivery and intrauterine growth restriction. In the adolescents, we evaluated central adiposity using the dual X-ray energy absorptiometry method. The indicators of central fat used were the trunk-to-total fat mass ratio (T/T), the android-to-gynoid fat mass ratio (A/G), the trunk-to-limb fat mass ratio (T/Lb), and the trunk-to-leg fat mass ratio (T/Lg). A theoretical model for the study of associations was developed using directed acyclic graphs, which allowed selecting the variables that required minimum adjustment for inclusion in the predictive model of exposure to cesarean delivery. The data were analyzed with marginal structural models weighted by the inverse of the probability of selection. A total of 38.6% of the adolescents studied were delivered by cesarean section. There was no significant difference in the central adiposity of adolescents delivered by cesarean section according to the indicators used: T/T ( coefficient = -0.003; 95%CI: -0.013; 0.007), A/G (coefficient = 0.001; 95%CI: -0.015; 0.018); T/Lb (coefficient = -0.016; 95%CI: -0.048; 0.016); T/Lg (coefficient = 0.014; 95%CI: -0.060; 0.030). In conclusion, there was no association between cesarean section delivery and greater central adiposity in the studied adolescents.

INFLUENCE OF THE AGE AT THE FIRST INSEMINATION ON THE PRODUCTIVE LONGEVITY OF BLACK AND WHITE AND KHOLMOGORY COWS

The influence of the age at the first fruitful insemination on the productive longevity of the blackand-white and Kholmogory cows in Udmurt republic was analysed. The study results are presented in the paper. The economic use period of the study cows did not have statistical differences and lasted 3,42–3,43 lactation periods. Black-and-white cows exceeded Kholmogory cows in the lifetime milk yield (by 3416,5 kg), fat content in milk (by 0,47 %) and milk amount in terms of basic standards (by 6317,7 kg) (P > 0,999). The optimal age for the first insemination of black-and-white cows can be considered 16–17 months, since insemination at the specified age ensures highest longevity in cows (3,85 lactations) and the highest lifetime milk yield indices (21347,8 kg), also expressed in terms of basic standards (27065,6 kg). Too early insemination of the black-and-white cows (up to 15 months) is not recommended, as it results in the decreased lifetime milk yields (up to 15491,4 kg), fat and protein content and shortens the economic use period of the animals up to 3,33 lactation periods. The lowest longevity (3,07 lactation periods) was observed in the black-and-white cows inseminated at the age of more than 20 months. The Kholmogory cows demonstrated an increase in lifetime milk yields (1084,5 kg (P > 0,95)) and the economic use period (1,05 lactation period (P > 0,999)) when the age of the first insemination was increased. However, as the fat mass ratio in milk decreased (by 0,06 % (P > 0,999)) and the protein mass ratio in milk fell (by 0,02 % (P > 0,999)), the increase in lifetime milk yield in terms of basic standards resulted from the increase in the age of the first insemination has no significant differences.

Maternal vomiting during early pregnancy and cardiovascular risk factors at school age: the Generation R Study

Background:Evidence suggests that low birth weight and fetal exposure to extreme maternal undernutrition is associated with cardiovascular disease in adulthood. Hyperemesis gravidarum, a clinical entity characterized by severe nausea and excess vomiting leading to a suboptimal maternal nutritional status during early pregnancy, is associated with an increased risk of adverse pregnancy outcomes. Several studies also showed that different measures related to hyperemesis gravidarum, such as maternal daily vomiting or severe weight loss, are associated with increased risks of adverse fetal pregnancy outcomes. Not much is known about long-term offspring consequences of maternal hyperemesis gravidarum and related measures during pregnancy. We examined the associations of maternal daily vomiting during early pregnancy, as a measure related to hyperemesis gravidarum, with childhood cardiovascular risk factors.Methods:In a population-based prospective cohort study from early pregnancy onwards among 4,769 mothers and their children in Rotterdam, the Netherlands, we measured childhood body mass index, total fat mass percentage, android/gynoid fat mass ratio, preperitoneal fat mass area, blood pressure, lipids, and insulin levels. We used multiple regression analyses to assess the associations of maternal vomiting during early pregnancy with childhood cardiovascular outcomes.Results:Compared with the children of mothers without daily vomiting during early pregnancy, the children of mothers with daily vomiting during early pregnancy had a higher childhood total body fat mass (difference 0.12 standard deviation score [SDS]; 95% confidence interval [CI] 0.03–0.20), android/gynoid fat mass ratio (difference 0.13 SDS; 95% CI 0.04–0.23), and preperitoneal fat mass area (difference 0.10 SDS; 95% CI 0–0.20). These associations were not explained by birth characteristics but partly explained by higher infant growth. Maternal daily vomiting during early pregnancy was not associated with childhood blood pressure, lipids, and insulin levels.Conclusions:Maternal daily vomiting during early pregnancy is associated with higher childhood total body fat mass and abdominal fat mass levels, but not with other cardiovascular risk factors. Further studies are needed to replicate these findings, to explore the underlying mechanisms and to assess the long-term consequences.