Outcomes of a Family Based Pediatric Obesity Program - Preliminary Results

Children that are classified as obese (body mass index (BMI) \u3e 95th percentile for age and sex, Centers for Disease Control and Prevention) have an increased risk for metabolic and cardiovascular complications. Family based programs that focus on physical activity (PA) and healthy eating are recommended for treatment of pediatric obesity. The purpose of the current study is to determine the outcomes of Building Healthy Families (BHF), a family-based pediatric weight loss treatment program composed of nutrition, physical activity and behavioral modification strategies. In addition, mediating variables that are associated with weight loss in children, in order to enhance the retention and success of this program will be identified. Twenty-two obese (\u3e95th percentile BMI) children (age: 9.94 ± 1.58 yrs) volunteered to participate. Children and their parents (20 moms, 20 dads, 68% obese; BMI \u3e 30 kg•m‾²) participated in weekly nutrition education, family lifestyle PA, and one-on-one meetings with a behavioral psychologist. Overall, child participants lost an average of 2.3 ± 2.0 kg of body mass in 12 weeks while parents lost 6.4 ± 4.3 kg of their body mass. There was a significant inverse association between percentage of program goals met and weight loss (r = -0.67, p \u3c 0.05). Decreases in the child participants intake of high fat, high calorie foods significantly predicted weight change (R2=0.98, p\u3c0.05). In conclusion, family based pediatric obesity programs may offer significant benefits and lead to healthier lifestyles for obese children and their parents

Effects of statins on metabolic adaptations to aerobic exercise training : preliminary findings [abstract]

Emerging evidence suggests statins, unlike exercise, may cause deleterious effects on skeletal muscle oxidative capacity and insulin sensitivity. The purpose of this study was to determine if daily statin therapy altered the ability of exercise to lower fasting plasma insulin and glucose and improve cardiorespiratory fitness

Temporal patterns of gene regulation and upstream regulators contributing to major developmental transitions during Rhesus macaque preimplantation development

The preimplantation period of life in mammals encompasses a tremendous amount of restructuring and remodeling of the embryonic genome and reprogramming of gene expression. These vast changes support metabolic activation and cellular processes that drive early cleavage divisions and enable the creation of the earliest primitive cell lineages. A major question in mammalian embryology is how such vast, sweeping changes in gene expression are orchestrated, so that changes in gene expression are exactly appropriate to meet the developmental needs of the embryo over time. Using the rhesus macaque as an experimentally tractable model species closely related to the human, we combined high quality RNA-seq libraries, in-depth sequencing and advanced systems analysis to discover the underlying mechanisms that drive major changes in gene regulation during preimplantation development. We identified the major changes in mRNA population and the biological pathways and processes impacted by those changes. Most importantly, we identified 24 key upstream regulators that are themselves modulated during development and that are associated with the regulation of over 1000 downstream genes. Through their roles in extensive gene networks, these 24 upstream regulators are situated to either drive major changes in target gene expression or modify the cellular environment in which other genes function, thereby directing major developmental transitions in the preimplantation embryo. The data presented here highlight some of the specific molecular features that likely drive preimplantation development in a nonhuman primate species and provides an extensive database for novel hypothesis-driven studies

Altered Hepatic Lipid Metabolism Contributes to Nonalcoholic Fatty Liver Disease in Leptin-Deficient Ob/Ob Mice

Nonalcoholic fatty liver disease (NAFLD) is strongly linked to obesity, insulin resistance, and abnormal hepatic lipid metabolism; however, the precise regulation of these processes remains poorly understood. Here we examined genes and proteins involved in hepatic oxidation and lipogenesis in 14-week-old leptin-deficient Ob/Ob mice, a commonly studied model of obesity and hepatic steatosis. Obese Ob/Ob mice had increased fasting glucose, insulin, and calculated HOMA-IR as compared with lean wild-type (WT) mice. Ob/Ob mice also had greater liver weights, hepatic triglyceride (TG) content, and markers of de novo lipogenesis, including increased hepatic gene expression and protein content of acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), and stearoyl-CoA desaturase-1 (SCD-1), as well as elevated gene expression of PPARγ and SREBP-1c compared with WT mice. While hepatic mRNA levels for PGC-1α, PPARα, and TFAM were elevated in Ob/Ob mice, measures of mitochondrial function (β-HAD activity and complete (to CO2) and total mitochondrial palmitate oxidation) and mitochondrial OXPHOS protein subunits I, III, and V content were significantly reduced compared with WT animals. In summary, reduced hepatic mitochondrial content and function and an upregulation in de novo lipogenesis contribute to obesity-associated NAFLD in the leptin-deficient Ob/Ob mouse

Associations between Maternal Diet, Body Composition and Gut Microbial Ecology in Pregnancy

Maternal body composition, gestational weight gain (GWG) and diet quality influence offspring obesity risk. While the gut microbiome is thought to play a crucial role, it is understudied in pregnancy. Using a longitudinal pregnancy cohort, maternal anthropometrics, body composition, fecal microbiome and dietary intake were assessed at 12, 24 and 36 weeks of gestation. Fecal samples (n = 101, 98 and 107, at each trimester, respectively) were utilized for microbiome analysis via 16S rRNA amplicon sequencing. Data analysis included alpha- and beta-diversity measures and assessment of compositional changes using MaAsLin2. Correlation analyses of serum metabolic and anthropometric markers were performed against bacterial abundance and predicted functional pathways. α-diversity was unaltered by pregnancy stage or maternal obesity status. Actinobacteria, Lachnospiraceae, Akkermansia, Bifidobacterium, Streptococcus and Anaerotuncus abundances were associated with gestation stage. Maternal obesity status was associated with increased abundance of Lachnospiraceae, Bilophila, Dialister and Roseburia. Maternal BMI, fat mass, triglyceride and insulin levels were positively associated with Bilophila. Correlations of bacterial abundance with diet intake showed that Ruminococcus and Paraprevotella were associated with total fat and unsaturated fatty acid intake, while Collinsella and Anaerostipes were associated with protein intake. While causal relationships remain unclear, collectively, these findings indicate pregnancy- and maternal obesity-dependent interactions between dietary factors and the maternal gut microbiome

Maternal nutritional status modifies heat-associated growth restriction in women with chronic malnutrition

Rapid changes in the global climate are deepening existing health disparities from resource scarcity and malnutrition. Rising ambient temperatures represent an imminent risk to pregnant women and infants. Both maternal malnutrition and heat stress during pregnancy contribute to poor fetal growth, the leading cause of diminished child development in low-resource settings. However, studies explicitly examining interactions between these two important environmental factors are lacking. We leveraged maternal and neonatal anthropometry data from a randomized controlled trial focused on improving preconception maternal nutrition (Women First Preconception Nutrition trial) conducted in Thatta, Pakistan, where both nutritional deficits and heat stress are prevalent. Multiple linear regression of ambient temperature and neonatal anthropometry at birth (n = 459) showed a negative association between daily maximal temperatures in the first trimester and Z-scores of birth length and head circumference. Placental mRNA-sequencing and protein analysis showed transcriptomic changes in protein translation, ribosomal proteins, and mTORC1 signaling components in term placenta exposed to excessive heat in the first trimester. Targeted metabolomic analysis indicated ambient temperature associated alterations in maternal circulation with decreases in choline concentrations. Notably, negative impacts of heat on birth length were in part mitigated in women randomized to comprehensive maternal nutritional supplementation before pregnancy suggesting potential interactions between heat stress and nutritional status of the mother. Collectively, the findings bridge critical gaps in our current understanding of how maternal nutrition may provide resilience against adverse effects of heat stress in pregnanc