ABSTRACT: Pregestational overweight and obesity are connected with differences in gut microbiota composition and systemic inflammation at third trimester
Project description:The gut microbiota has been implicated in obesity and cardiometabolic diseases, although evidence in humans is scarce. We investigated how gut microbiota manipulation by antibiotics (7-day administration of amoxicillin, vancomycin, or placebo) affects host metabolism in 57 obese, prediabetic men. Vancomycin, but not amoxicillin, decreased bacterial diversity and reduced Firmicutes involved in short-chain fatty acid and bile acid metabolism, concomitant with altered plasma and/or fecal metabolite concentrations. Adipose tissue gene expression of oxidative pathways was upregulated by antibiotics, whereas immune-related pathways were downregulated by vancomycin. Antibiotics did not affect tissue-specific insulin sensitivity, energy/substrate metabolism, postprandial hormones and metabolites, systemic inflammation, gut permeability, and adipocyte size. Importantly, energy harvest, adipocyte size, and whole-body insulin sensitivity were not altered at 8-week follow-up, despite a still considerably altered microbial composition, indicating that interference with adult microbiota by 7-day antibiotic treatment has no clinically relevant impact on metabolic health in obese humans. This randomized, placebo-controlled, double-blind study had a 3-armed parallel design. Overweight/obese participants were randomized to oral intake of amoxicillin, vancomycin or placebo for 7 consecutive days. After an overnight fast, subcutaneous adipose tissue biopsies were taken that were subjected to gene expression profiling by array.
Project description:The aim of study was to investigate correlation bewteen peripheral blood mononuclear cell (PBMC) transcriptome profiles and plasma lipid profiles of Korean adult with varying BMI. In Korean, BMI cut-off points are 18.5~22.9 kg/m2 (normal range), M-bM-^IM-% 23 kg/m2 (overweight), M-bM-^IM-% 25 kg/m2 (obese), M-bM-^IM-% 30 kg/m2 (severely obese). Thus, the obese group was subdivided into mildly obese (BMI 25~27 kg/m2, OA) and highly obese (BMI 27~30 kg/m2, OB). This study indicates that lipid, glucose and inflammation metabolism-related gene expressions were altered according to cahnge of varing phenotype biomarkers such as BMI, plasma total-C, TG, FFA and HDL-C. Thus, blood biomarkers and PBMC gene expression profiles identified in this study may be useful as indicative biomarkers for obese susceptibility in Korean adult as well as response to various intervention for treating obesity. Total RNA of PBMCs was obtained from normal weight, obese person and mRNA expression was measured.
Project description:Preeclampsia is one of the leading causes of maternal death worldwide. While the root cause is still unknown, the underlying biology of the disorder is becoming more clear. We recently published a study showing large, significant differences in DNA methylation in 3rd trimester placental samples associated with early-onset preeclampsia (EOPET) compared to controls. In this study, to identify DNA methylation differences associated with preeclampsia that occur early in pregnancy and to further delineate common EOPET-associated differences, we utilized a genetic defect, trisomy 16 (T16), that is predisposing to preeclampsia. We ran T16 placental samples from the 1st trimester (n=5) and 3rd trimester (n=10) against gestational age matched controls on the Illumina Infinium HumanMethylation450 BeadChip. Third trimester samples were from pregnancies with T16 confined to the placenta (confined placental mosaicism 16;CPM16), and consisted of samples that were and were not associated with EOPET (n=5 each). We identified a large number of DNA methylation differences in CPM16 samples compared to controls using stringent criteria (n=2254;False Discovery Rate <0.01, ->0.15). Several of these differences (11%) overlapped differences observed in chromosomally normal EOPET using similarly stringent criteria (FDR<0.01;->0.125). Isolating EOPET-associated probes produced a similar - distribution amongst CPM16 samples, although samples associated with EOPET showed a tendency towards larger DNA methylation differences. We also identified 262 DNA methylation differences between 1st trimester T16 and 1st trimester controls. Of these, 77 overlapped differences seen in 3rd trimester CPM16. Investigating these 77 T16/CPM16 specific DNA methylation differences, we identified three probes near two genes (ARGHEF37 and JUNB) that were also present as EOPET-associated methylation differences. In summary, we identified significant overlapping DNA methylation profiles of placentas with T16 and chromosomally normal placentas associated with EOPET. Specific DNA methylation marks within these profiles may be of future clinical utility in early identification of pregnancies susceptible to EOPET. Bisulfite converted DNA from 5 1st trimester trisomy 16 placentas, 5 chromosomally normal 1st trimester placentas, 10 third trimester placentas from confined placental mosaicism placentas and 10 chromosomally normal 3rd trimester placentas
Project description:Human placenta bulk small RNA-seq from healthy pregnancies without infertility, from n=113 first trimester (58 female, 55 male) and n=47 third trimester (19 female, 28 male) tissue samples. Tissue was collected at Cedars-Sinai Medical Center in Los Angeles, California, USA. First trimester placenta was collected at 70-102 days of gestation from leftover chorionic villus sampling for prenatal genetic diagnosis. Third trimester placenta was collected after delivery at 254-290 days gestation from the fetal side near the umbilical cord insertion site beneath the amnion. Mothers with pre-existing diabetes or hypertension were excluded. All pregnancies were conceived without fertility treatments, were normal karyotype, and resulted in live singleton births. The average parental age was advanced (over 35 years old) but PCA analysis did not show clustering by either maternal or paternal age. Gonzalez et al 2021 [PMID: 34030457] analyzes similarities and differences between first and third trimester miRNA expression overall. Flowers et al 2021 focuses on the effect of fetal sex on miRNA expression across gestation.
Project description:Influenza A virus (IAV) causes a wide range of extra-respiratory complications, ranging from central nervous system disease to cardiac disease. Obesity/overweight has previously been identified as a susceptibility factor for both severe influenza and cardiac disease. We therefore sought to investigate the systemic pathogenesis of influenza in an obese mouse model with a focus on cardiac complications of influenza.
Project description:To investigate the role of miRNA in the placental development, we analyzed miRNA expression profiles in the first and third trimester human placentas. Total RNA was isolated from 12 placentas (6 from first trimester and 6 from third trimester). miRNA expression profiles were determined by Affymetrix GeneChip 2.0 miRNA Microarray.
Project description:The aim of study was to investigate correlation bewteen peripheral blood mononuclear cell (PBMC) transcriptome profiles and plasma lipid profiles of Korean adult with varying BMI. In Korean, BMI cut-off points are 18.5~22.9 kg/m2 (normal range), ≥ 23 kg/m2 (overweight), ≥ 25 kg/m2 (obese), ≥ 30 kg/m2 (severely obese). Thus, the obese group was subdivided into mildly obese (BMI 25~27 kg/m2, OA) and highly obese (BMI 27~30 kg/m2, OB). This study indicates that lipid, glucose and inflammation metabolism-related gene expressions were altered according to cahnge of varing phenotype biomarkers such as BMI, plasma total-C, TG, FFA and HDL-C. Thus, blood biomarkers and PBMC gene expression profiles identified in this study may be useful as indicative biomarkers for obese susceptibility in Korean adult as well as response to various intervention for treating obesity.
Project description:In order to explore the effect of hypertension and overweight/obesity on human visceral adipose tissue transcriptome, we collected three visceral adipose tissue samples from normal weight individuals (non hypertension), overweight/obese individuals (non hypertension) and overweight/obese individuals with hypertension, and sequenced their transcriptome.
Project description:Tissue inflammation is a key factor underlying insulin resistance in established obesity. Several models of immuno-compromised mice are protected from obesity-induced insulin resistance. However, it is unanswered whether inflammation triggers systemic insulin resistance or vice versa in obesity. The purpose of this study was to assess these questions. 8-week-old C57BL/6J male mice was treated with 60% HFD for 0 day (NCD), 3 days, and 7 days. Eipididymal fat was fractionated. Each groups have three replicates.
Project description:To investigate the role of miRNA in the placental development, we analyzed miRNA expression profiles in the first and third trimester human placentas. Total RNA was isolated from 12 placentas (6 from first trimester and 6 from third trimester). miRNA expression profiles were determined by Affymetrix GeneChip 2.0 miRNA Microarray. Using miRNA microarray to determine miRNA expression profiles in the human placenta between first and third trimester pregnancies.