Maternal under-nutrition during pregnancy alters the molecular response to over-nutrition in multiple organs and tissues in nonhuman primate juvenile offspring.

Previous studies in rodents suggest that mismatch between fetal and postnatal nutrition predisposes individuals to metabolic diseases. We hypothesized that in nonhuman primates (NHP), fetal programming of maternal undernutrition (MUN) persists postnatally with a dietary mismatch altering metabolic molecular systems that precede standard clinical measures. We used unbiased molecular approaches to examine response to a high fat, high-carbohydrate diet plus sugar drink (HFCS) challenge in NHP juvenile offspring of MUN pregnancies compared with controls (CON).

Erratum: Ancestral diversity improves discovery and fine-mapping of genetic loci for anthropometric traits-The Hispanic/Latino Anthropometry Consortium.

[This corrects the article DOI: 10.1016/j.xhgg.

Hepatic transcript signatures predict atherosclerotic lesion burden prior to a 2-year high cholesterol, high fat diet challenge.

The purpose of this study was to identify molecular mechanisms by which the liver influences total lesion burden in a nonhuman primate model (NHP) of cardiovascular disease with acute and chronic feeding of a high cholesterol, high fat (HCHF) diet. Baboons (47 females, 64 males) were fed a HCHF diet for 2 years (y); liver biopsies were collected at baseline, 7 weeks (w) and 2y, and lesions were quantified in aortic arch, descending aorta, and common iliac at 2y. Unbiased weighted gene co-expression network analysis (WGCNA) revealed several modules of hepatic genes correlated with lesions at different time points of dietary challenge.

Genetic variants in ALDH1L1 and GLDC influence the serine-to-glycine ratio in Hispanic children.

Background: Glycine is a proteogenic amino acid that is required for numerous metabolic pathways, including purine, creatine, heme, and glutathione biosynthesis. Glycine formation from serine, catalyzed by serine hydroxy methyltransferase, is the major source of this amino acid in humans. Our previous studies in a mouse model have shown a crucial role for the 10-formyltetrahydrofolate dehydrogenase enzyme in serine-to-glycine conversion.

Ancestral diversity improves discovery and fine-mapping of genetic loci for anthropometric traits-The Hispanic/Latino Anthropometry Consortium.

Hispanic/Latinos have been underrepresented in genome-wide association studies (GWAS) for anthropometric traits despite their notable anthropometric variability, ancestry proportions, and high burden of growth stunting and overweight/obesity. To address this knowledge gap, we analyzed densely imputed genetic data in a sample of Hispanic/Latino adults to identify and fine-map genetic variants associated with body mass index (BMI), height, and BMI-adjusted waist-to-hip ratio (WHRadjBMI). We conducted a GWAS of 18 studies/consortia as part of the Hispanic/Latino Anthropometry (HISLA) Consortium (stage 1, n = 59,771) and generalized our findings in 9 additional studies (stage 2, n = 10,538).

Replication of Integrative Data Analysis for Adipose Tissue Dysfunction, Low-Grade Inflammation, Postprandial Responses and OMICs Signatures in Symptom-Free Adults.

We previously reported preliminary characterization of adipose tissue (AT) dysfunction through the adiponectin/leptin ratio (ALR) and fasting/postprandial (F/P) gene expression in subcutaneous (SQ) adipose tissue (AT) biopsies obtained from participants in the GEMM study, a precision medicine research project. Here we present integrative data replication of previous findings from an increased number of GEMM symptom-free (SF) adults (N = 124) to improve characterization of early biomarkers for cardiovascular (CV)/immunometabolic risk in SF adults with AT dysfunction. We achieved this goal by taking advantage of the rich set of GEMM F/P 5 h time course data and three tissue samples collected at the same time and frequency on each adult participant (F/P blood, biopsies of SQAT and skeletal muscle (SKM)).

Genetic determinants of metabolic biomarkers and their associations with cardiometabolic traits in Hispanic/Latino adolescents.

Background: Metabolic regulation plays a significant role in energy homeostasis, and adolescence is a crucial life stage for the development of cardiometabolic disease (CMD). This study aims to investigate the genetic determinants of metabolic biomarkers-adiponectin, leptin, ghrelin, and orexin-and their associations with CMD risk factors.

Methods: We characterized the genetic determinants of the biomarkers among Hispanic/Latino adolescents of the Santiago Longitudinal Study (SLS) and identified the cumulative effects of genetic variants on adiponectin and leptin using biomarker polygenic risk scores (PRS).

Genetic variants and physical activity interact to affect bone density in Hispanic children.

Background: Our aim was to investigate if moderate to vigorous physical activity (MVPA), calcium intake interacts with bone mineral density (BMD)-related single nucleotide polymorphisms (SNPs) to influence BMD in 750 Hispanic children (4-19y) of the cross-sectional Viva La Familia Study.

Methods: Physical activity and dietary intake were measured by accelerometers and multiple-pass 24 h dietary recalls, respectively. Total body and lumbar spine BMD were measured by dual energy X-ray absorptiometry.

Towards precision medicine: defining and characterizing adipose tissue dysfunction to identify early immunometabolic risk in symptom-free adults from the GEMM family study.

Interactions between macrophages and adipocytes are early molecular factors influencing adipose tissue (AT) dysfunction, resulting in high leptin, low adiponectin circulating levels and low-grade metaflammation, leading to insulin resistance (IR) with increased cardiovascular risk. We report the characterization of AT dysfunction through measurements of the adiponectin/leptin ratio (ALR), the adipo-insulin resistance index (Adipo-IRi), fasting/postprandial (F/P) immunometabolic phenotyping and direct F/P differential gene expression in AT biopsies obtained from symptom-free adults from the GEMM family study. AT dysfunction was evaluated through associations of the ALR with F/P insulin-glucose axis, lipid-lipoprotein metabolism, and inflammatory markers.

Heritability and genetic correlations of obesity indices with ambulatory and office beat-to-beat blood pressure in the Oman Family Study.

Objective: To more precisely and comprehensively estimate the genetic and environmental correlations between various indices of obesity and BP.

Methods: We estimated heritability and genetic correlations of obesity indices with BP in the Oman family study (n = 1231). Ambulatory and office beat-to-beat BP was measured and mean values for SBP and DBP during daytime, sleep, 24-h and 10 min at rest were calculated.

Genetic variants affecting bone mineral density and bone mineral content at multiple skeletal sites in Hispanic children.

Context: Osteoporosis is a major public health burden with significant economic costs. However, the correlates of bone health in Hispanic children are understudied.

Objective: We aimed to identify genetic variants associated with bone mineral density (BMD) and bone mineral content (BMC) at multiple skeletal sites in Hispanic children.

Exenatide regulates pancreatic islet integrity and insulin sensitivity in the nonhuman primate baboon Papio hamadryas.

The glucagon-like peptide-1 receptor agonist exenatide improves glycemic control by several and not completely understood mechanisms. Herein, we examined the effects of chronic intravenous exenatide infusion on insulin sensitivity, β cell and α cell function and relative volumes, and islet cell apoptosis and replication in nondiabetic nonhuman primates (baboons). At baseline, baboons received a 2-step hyperglycemic clamp followed by an l-arginine bolus (HC/A).

A trans-ancestral meta-analysis of genome-wide association studies reveals loci associated with childhood obesity.

Although hundreds of genome-wide association studies-implicated loci have been reported for adult obesity-related traits, less is known about the genetics specific for early-onset obesity and with only a few studies conducted in non-European populations to date. Searching for additional genetic variants associated with childhood obesity, we performed a trans-ancestral meta-analysis of 30 studies consisting of up to 13 005 cases (≥95th percentile of body mass index (BMI) achieved 2-18 years old) and 15 599 controls (consistently <50th percentile of BMI) of European, African, North/South American and East Asian ancestry. Suggestive loci were taken forward for replication in a sample of 1888 cases and 4689 controls from seven cohorts of European and North/South American ancestry.

Analysis of serum changes in response to a high fat high cholesterol diet challenge reveals metabolic biomarkers of atherosclerosis.

Atherosclerotic plaques are characterized by an accumulation of macrophages, lipids, smooth muscle cells, and fibroblasts, and, in advanced stages, necrotic debris within the arterial walls. Dietary habits such as high fat and high cholesterol (HFHC) consumption are known risk factors for atherosclerosis. However, the key metabolic contributors to diet-induced atherosclerosis are far from established.

Genomewide association study of C-peptide surfaces key regulatory genes in Indians.

Insulin is a commonly used measure of pancreatic β-cell function but exhibits a short half-life in the human body. During biosynthesis, insulin release is accompanied by C-peptide at an equimolar concentration which has a much higher plasma half-life and is therefore projected as a precise measure of β-cell activity than insulin. Despite this, genetic studies of metabolic traits haveneglected the regulatory potential of C-peptide for therapeutic intervention of type-2 diabetes.

Heritability and genetic and environmental correlations of heart rate variability and baroreceptor reflex sensitivity with ambulatory and beat-to-beat blood pressure.

This family study from Oman (n = 1231) explored the heritability and genetic and environmental correlations of heart rate variability (HRV) and baroreceptor reflex sensitivity (BRS) with ambulatory and beat-to-beat blood pressure (BP). Ambulatory BP was measured for 24 hours to calculate mean values for daytime and sleep separately. Time and frequency domain HRV indices, BRS, office beat-to-beat BP, and heart rate (HR) were measured for 10 minutes at rest.

Duodenal adipose tissue is associated with obesity in baboons (Papio sp): a novel site of ectopic fat deposition in non-human primates.

Aims: Ectopic fat is a recognized contributor to insulin resistance and metabolic dysfunction, while the role of fat deposition inside intestinal wall tissue remains understudied. We undertook this study to directly quantify and localize intramural fat deposition in duodenal tissue and determine its association with adiposity.

Methods: Duodenal tissues were collected from aged (21.

Heritability and genetic correlations of heart rate variability at rest and during stress in the Oman Family Study.

Introduction: Individual differences in heart rate variability (HRV) can be partly attributed to genetic factors that may be more pronounced during stress. Using data from the Oman Family Study (OFS), we aimed to estimate and quantify the relative contribution of genes and environment to the variance of HRV at rest and during stress; calculate the overlap in genetic and environmental influences on HRV at rest and under stress using bivariate analyses of HRV parameters and heart rate (HR).

Methods: Time and frequency domain HRV variables and average HR were measured from beat-to-beat HR obtained from electrocardiogram recordings at rest and during two stress tests [mental: Word Conflict Test (WCT) and physical: Cold Pressor Test (CPT)] in the OFS - a multigenerational pedigree consisting of five large Arab families with a total of 1326 participants.

Sex-dimorphic acceleration of pericardial, subcutaneous, and plasma lipid increase in offspring of poorly nourished baboons.

Developmental programming by reduced maternal nutrition alters function in multiple offspring physiological systems, including lipid metabolism. We have shown that intrauterine growth restriction (IUGR) leads to offspring cardiovascular dysfunction with an accelerated aging phenotype in our nonhuman primate, baboon model. We hypothesized age-advanced pericardial fat and blood lipid changes.

Genetic and environmental (physical fitness and sedentary activity) interaction effects on cardiometabolic risk factors in Mexican American children and adolescents.

Knowledge on genetic and environmental (G × E) interaction effects on cardiometabolic risk factors (CMRFs) in children is limited.  The purpose of this study was to examine the impact of G × E interaction effects on CMRFs in Mexican American (MA) children (n = 617, ages 6-17 years). The environments examined were sedentary activity (SA), assessed by recalls from "yesterday" (SAy) and "usually" (SAu) and physical fitness (PF) assessed by Harvard PF scores (HPFS).

Assessment of DNA Methylation Patterns in the Bone and Cartilage of a Nonhuman Primate Model of Osteoarthritis.

Objective: Osteoarthritis (OA) affects humans and several other animals. Thus, the mechanisms underlying this disorder, such as specific skeletal tissue DNA methylation patterns, may be evolutionary conserved. However, associations between methylation and OA have not been readily studied in nonhuman animals.

Use and Importance of Nonhuman Primates in Metabolic Disease Research: Current State of the Field.

Obesity and its multiple metabolic sequelae, including type 2 diabetes, cardiovascular disease, and fatty liver disease, are becoming increasingly widespread in both the developed and developing world. There is an urgent need to identify new approaches for the prevention and treatment of these costly and prevalent metabolic conditions. Accomplishing this will require the use of appropriate animal models for preclinical and translational investigations in metabolic disease research.

Nonhuman Primates and Translational Research-Cardiovascular Disease.

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the United States. Human epidemiological studies provide challenges for understanding mechanisms that regulate initiation and progression of CVD due to variation in lifestyle, diet, and other environmental factors. Studies describing metabolic and physiologic aspects of CVD, and those investigating genetic and epigenetic mechanisms influencing CVD initiation and progression, have been conducted in multiple Old World nonhuman primate (NHP) species.

Ensuring due process in the IACUC and animal welfare setting: considerations in developing noncompliance policies and procedures for institutional animal care and use committees and institutional officials.

Every institution that is involved in research with animals is expected to have in place policies and procedures for the management of allegations of noncompliance with the Animal Welfare Act and the U.S. Public Health Service Policy on the Humane Care and Use of Laboratory Animals.