Maternal obesity is present in 20-34% of pregnant women and has been associated with both intrauterine growth restriction and large-for-gestational age fetuses. While fetal and placental functions have been extensively studied in the baboon, no data are available on the effect of maternal obesity on placental structure and function in this species. We hypothesize that maternal obesity in the baboon is associated with a maternal inflammatory state and induces structural and functional changes in the placenta. The major findings of this study were 1) decreased placental syncytiotrophoblast amplification factor, intact syncytiotrophoblast endoplasmic reticulum structure and decreased system A placental amino acid transport in obese animals; 2) fetal serum amino acid composition and mononuclear cells (PBMC) transcriptome were different in fetuses from obese compared with non-obese animals 3) maternal obesity in humans and baboons is similar in regard of increased placental and adipose tissue macrophage infiltration, increased CD14 expression in maternal PBMC and maternal hyperleptinemia. In summary, these data demonstrate that in obese baboons in the absence of increased fetal weight, placental and fetal phenotype are consistent with those described for large-for-gestational age human fetuses.

OBJECTIVE-To quantitate insulin sensitivity in lean and obese nondiabetic baboons and examine the underlying cellular/ molecular mechanisms responsible for impaired insulin action to characterize a baboon model of insulin resistance.RESEARCH DESIGN AND METHODS-Twenty baboons received a hyperinsulinemic-euglycemic clamp with skeletal muscle and visceral adipose tissue biopsies at baseline and at 30 and 120 min after insulin. Genes and protein expression of key molecules involved in the insulin signaling cascade (insulin receptor, insulin receptor substrate-1, p85, phosphatidylinositol 3-kinase, Akt, and AS160) were sequenced, and insulin-mediated changes were analyzed.RESULTS-Overall, baboons show a wide range of insulin sensitivity (6.2 Ϯ 4.8 mg ⅐ kg Ϫ1 ⅐ min Ϫ1 ), and there is a strong inverse correlation between indexes of adiposity and insulin sensitivity (r ϭ Ϫ0.946, P Ͻ 0.001 for % body fat; r ϭ Ϫ0.72, P Ͻ 0.001 for waist circumference). The genes and protein sequences analyzed were found to have ϳ98% identity to those of man. Insulin-mediated changes in key signaling molecules were impaired both in muscle and adipose tissue in obese insulinresistant compared with lean insulin-sensitive baboons. CONCLUSIONS-The obese baboon is a pertinent nonhuman primate model to examine the underlying cellular/molecular mechanisms responsible for insulin resistance and eventual development of type 2 diabetes. Diabetes 57:899-908, 2008 I nsulin resistance is characterized by impaired response of target organs (e.g., skeletal muscle, liver, adipose tissue, and heart) to the physiological effects of insulin and results in impaired glucose metabolism. Insulin resistance is a characteristic feature of many common metabolic disorders, including obesity, type 2 diabetes, hypertension, and dyslipidemia, and of the normal aging process, which collectively constitute risk factors for the development of atherosclerotic cardiovascular disease (1-3).Nonhuman primates occupy a unique place in biomedical and evolutionary research by virtue of their close genetic and physiological similarity to humans and represent a valuable model that has great relevance to the study of human disease. Old World monkeys, which recently (ϳ25 millions years ago in evolutionary terms) diverged from the Hominoidea, have been most extensively studied (4,5). This taxonomic group includes vervet monkeys (Chlorocebus aethiops), rhesus macaques (Macaca mulatta), cynomolgus monkeys (Macaca fascicularis), and baboons (Papio hamadryas) (6). Despite the relevance of primate study to human disease research, there has been a shortage of primates available for biomedical research (7). Baboons and humans share great genetic similarity, with ϳ96% homology evident at the DNA level (8). The sequences of specific genes and the arrangements of genetic loci on chromosomes reflect the close evolutionary relationship between these two species (9). Not surprisingly, nonhuman primates develop many diseases similar to those in man, and they have been used as a model for osteoporos...

Type 2 diabetes (T2D) is a global epidemic that affects more than 8% of the world’s population and is a leading cause of death in Mexico. Diet and lifestyle are known to contribute to the onset of T2D. However, the role of the gut microbiome in T2D progression remains uncertain. Associations between microbiome composition and diabetes are confounded by medication use, diet, and obesity.Here we present data on a treatment-naive cohort of 405 Mexican individuals across varying stages of T2D severity. Associations between gut bacteria and more than 200 clinical variables revealed a defined set of bacterial genera that were consistent biomarkers of T2D prevalence and risk. Specifically, gradual increases in blood glucose levels, beta cell dysfunction, and the accumulation of measured T2D risk factors were correlated with the relative abundances of four bacterial genera. In a cohort of 25 individuals, T2D treatment—predominantly metformin—reliably returned the microbiome to the normoglycemic community state. Deep clinical characterization allowed us to broadly control for confounding variables, indicating that these microbiome patterns were independent of common T2D comorbidities, like obesity or cardiovascular disease. Our work provides the first solid evidence for a direct link between the gut microbiome and T2D in a critically high-risk population. In particular, we show that increased T2D risk is reflected in gradual changes in the gut microbiome. Whether or not these T2D-associated changes in the gut contribute to the etiology of T2D or its comorbidities remains to be seen.

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High levels of plasma homocysteine are associated with an increased risk of many health conditions influenced by both environmental and genetic factors. The objective of this study was to provide the geographical distribution of folate pathway genetic polymorphisms in Mexico and the comparison with the reported frequencies in different continental populations. This study included the analysis of the genotypic frequencies of eight polymorphisms in genes of the folate/homocysteine metabolic pathway in 1,350 Mestizo and Amerindian subjects from different regions in Mexico and 836 individuals from European, African and Asian populations of the 1,000 Genomes Project. In Mexican Mestizo and Amerindian populations, the MTHFR C677T risk genotype (TT) was highly prevalent (frequency: 25 and 57 %, respectively). In Mestizos, the frequency showed clear regional variation related to ancestry; the Guerrero subpopulation with the highest Amerindian contribution had the highest TT frequency (33 %). The MTHFD1 G1958A AA risk genotype was also enriched in Mexican Mestizos and Amerindians (frequency: 34 and 58 %, respectively), whereas in African and Asian ancestry populations the frequency for AA was low (~4 %). All together risk genotypes showed regional differences, and Sonora had significantly different genetic frequencies compared with the other regions (P value <0.05). Our study illustrates differential geographical distribution of the risk variants in the folate/homocysteine metabolic pathway relative to ethnic background. This work supports that certain areas of the world have increased needs for folic acid and vitamin B supplementation, and this information needs to be considered in public health guidelines and eventually policies.Electronic supplementary materialThe online version of this article (doi:10.1007/s12263-014-0421-7) contains supplementary material, which is available to authorized users.