Intranasal oxytocin in lean and obese men
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo Sapiens
TISSUE(S): Blood
DISEASE(S): Obesity
PROVIDER: ST000770 | MetabolomicsWorkbench |
REPOSITORIES: MetabolomicsWorkbench
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Project description:Obesity is a frightening chronic disease, which has tripled since 1975. It is not expected to slow down staying one of the leading cases of preventable death and resulting in an increased clinical and economic burden. Poor lifestyle choices and excessive intake of “cheap calories” are major contributors to obesity, triggering type 2 diabetes, cardiovascular diseases, and other comorbidities. Understanding the molecular mechanisms responsible for development of obesity is essential as it might result in development of early-stage obesity biomarkers, allowing distinguish between metabolic syndromes and anti-obesity targets. The complex nature of this disease, coupled with the phenomenon of metabolically healthy obesity, inspired us to perform data-centric, hypothesis-generating pilot research, aimed to find correlations between parameters of classic clinical blood tests and proteomic profiles of 104 lean and obese subjects. As the result, we assembled patterns of proteins, which presence or absence allows predicting the weight of the patient fairly well. We believe that such proteomic patterns with high prediction power should facilitate the translation of potential candidates into biomarkers of clinical use for early-stage stratification of obesity therapy.
2021-09-10 | PXD023526 | Pride
Project description:Background & aimsDysbiosis of the gut microbiota in response to an energy-rich Western diet and the potential leak of bacteria and/or bacterial products from the intestine to the liver is perceived as a potential risk factor for the development of non-alcoholic fatty liver disease (NAFLD). We investigated the microbiome in liver biopsies from healthy lean and obese individuals and compared it with their blood microbiome.MethodsWe examined liver biopsies from 15 healthy lean and 14 obese individuals (BMI of 18.5-25 and 30-40 kg/m2, respectively). Bacterial 16S ribosomal DNA (rDNA) was analysed by quantitative polymerase chain reaction (qPCR) and 16S metagenomic sequencing targeting the hypervariable V3-V4 region. Metagenomic analysis was performed using the linear discriminant analysis effect size (LEfSe) algorithm. Data are medians with IQRs in brackets.ResultsHistology revealed hepatic steatosis in 13 obese individuals and in 2 lean individuals. A robust signal from qPCR revealed significantly higher amounts of bacterial rDNA copies in liver samples from obese individuals compared with those from lean individuals (148 [118-167] vs. 77 [62-122] 16S copies/ng DNA, p <0.001). Liver biopsies from the obese group were characterised by lower alpha diversity at the phylum level (Shannon index 0.60 [0.55-0.76] vs. 0.73 [0.62-0.90], p = 0.025), and metagenomic profiling revealed a significantly higher proportion of Proteobacteria in this group (81.0% [73.0-82.4%] vs. 74.3% [68.4-78.4%], p = 0.014).ConclusionsWe provide evidence for the presence of bacterial rDNA in the healthy human liver. Based on differences in the hepatic microbiome between obese individuals and healthy lean individuals, we suggest that changes in the liver microbiome could constitute an additional risk factor for the development of NAFLD.Lay summaryNon-alcoholic fatty liver disease (NAFLD) has become the most common liver disease globally, and new evidence suggests that obesity is associated with a disturbed gut bacterial composition, which may influence the development of NAFLD. We examined the composition of bacterial DNA in liver biopsies from healthy lean and obese individuals and found a different composition of bacterial DNA in liver biopsies from the obese group. We propose that the increased bacterial DNA load in the livers of obese individuals could constitute an early risk factor for the progression of NAFLD.Clinical trial numberNCT02337660.
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Project description:Conventional anaerobic digesters (ADs) treating dairy manure are fed with raw or fermented manure rich in volatile fatty acids (VFAs). In contrast, pre-fermented AD (PF-AD) is fed with the more recalcitrant, fiber-rich fraction of manure that has been pre-fermented and depleted of VFAs. Thus, the substrate of PF-AD may be likened to a lean diet rich in fibers while the pre-fermentation stage fermenter is fed a relatively rich diet containing labile organic substances. Previous results have shown that conventional and pre-fermented ADs fed with raw or pre-fermented manure, respectively, produced comparable methane yields. The primary objective of this study was to characterize, using next-generation DNA sequencing, the bacterial communities in various bioreactors (pre-fermentation stage fermenter; various operational arrangements PF-AD; conventional single-stage AD; and a full scale AD) and compare the Firmicutes to Bacteroidetes (F/B) ratios in these different systems. Firmicutes and Bacteroidetes constituted the two most abundant phyla in all AD samples analyzed, as well as most of the samples analyzed in the fermenters and manure samples. Higher relative abundance of Bacteroidetes, ranging from 26% to 51% of bacteria, tended to be associated with PF-AD samples, while the highest relative abundance of Firmicutes occurred in the fermenter (maximum of 76% of bacteria) and manure (maximum of 66% of bacteria) samples. On average, primary stage fermenters exhibited microbiological traits linked to obesity: higher F/B ratios and a 'diet' that is less fibrous and more labile compared to that fed to PF-AD. On the other hand, microbial characteristics associated with leanness (lower F/B ratios combined with fibrous substrate) were associated with PF-AD. We propose that bacterial communities in AD shift depending on the quality of substrate, which ultimately results in maintaining VFA yields in PF-AD, similar to the role of bacterial communities and a high fiber diet in lean mice.
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Project description:PurposeThis study assessed the perception of sweetness, creaminess, and pleasantness from a sweet/fat preference test in subjects who are lean (BMI: 19-25), obese (BMI: 30-33) or very obese (BMI: 34-40) using categorical modeling.MethodsSubjects tasted 16 dairy solutions consisting of 0%, 3.5%, 11.3% and 37.5% fat and each containing 0%, 5%, 10%, or 20% sugar and rated them for sweetness, creaminess and pleasantness.ResultsA proportional odds model described the perception of sweetness using an Emax for the effect of sugar and a linear effect for fat. Perception of creaminess was dependent on the fat and sugar content and was described with proportional odds model with linear effects of sugar and fat. Perception of pleasantness increased with sugar and fat but decreased in solutions containing 37.5% fat. A differential odds model using an Emax model for fat and sugar with a negative interaction between them allowed the sugar content to be less than proportional and the fat content to be greater than proportional for pleasantness.ConclusionsApplication of modeling provided understanding of these complex interactions of sugar and fat on the perception of sweetness, creaminess, and pleasantness and provides a tool to investigate obesity and pharmacological intervention.
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Project description:In order to determine whether dis-regulation of a genetic pathway could explain the increased apoptosis of parp-2-/- double positive thymocytes, the gene expression profiles in double positive thymocytes derived from wild-type and parp-2-/- mice were analysed using Affymetrix oligonucleotide chips (mouse genome 430 2.0).
2007-05-23 | E-MEXP-755 | biostudies-arrayexpress
Project description:The human distal gut harbours a vast ensemble of microbes (the microbiota) that provide important metabolic capabilities, including the ability to extract energy from otherwise indigestible dietary polysaccharides. Studies of a few unrelated, healthy adults have revealed substantial diversity in their gut communities, as measured by sequencing 16S rRNA genes, yet how this diversity relates to function and to the rest of the genes in the collective genomes of the microbiota (the gut microbiome) remains obscure. Studies of lean and obese mice suggest that the gut microbiota affects energy balance by influencing the efficiency of calorie harvest from the diet, and how this harvested energy is used and stored. Here we characterize the faecal microbial communities of adult female monozygotic and dizygotic twin pairs concordant for leanness or obesity, and their mothers, to address how host genotype, environmental exposure and host adiposity influence the gut microbiome. Analysis of 154 individuals yielded 9,920 near full-length and 1,937,461 partial bacterial 16S rRNA sequences, plus 2.14 gigabases from their microbiomes. The results reveal that the human gut microbiome is shared among family members, but that each person's gut microbial community varies in the specific bacterial lineages present, with a comparable degree of co-variation between adult monozygotic and dizygotic twin pairs. However, there was a wide array of shared microbial genes among sampled individuals, comprising an extensive, identifiable 'core microbiome' at the gene, rather than at the organismal lineage, level. Obesity is associated with phylum-level changes in the microbiota, reduced bacterial diversity and altered representation of bacterial genes and metabolic pathways. These results demonstrate that a diversity of organismal assemblages can nonetheless yield a core microbiome at a functional level, and that deviations from this core are associated with different physiological states (obese compared with lean).
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Project description:Adipose tissue stromal cells contribute to the regulation of adipose tissue in lean and obese states. Myeloid cells such as adipose tissue macrophages (ATMs) and dendritic cells (ATDCs) undergo both quantitative and qualitative changes with obesity. Due to similarity in markers the identify of adipose tissue dendritic cells and macrophages has been elusive. We have refined prior protocols to unambiguously discern ATM and ATDC in mice. We used microarrays to compare the profiles of ATMs and ATDC from gonadal adipose tissue from lean, obese, and formerly obese mice. We also isolated preadipocytes (PA) from lean and obese mice for comparison. Male C57Bl/6 mice were fed normal diet (ND) or high fat diet (HFD) for 16 weeks. Weight loss (WL) mice were switched from the HFD to ND for 8 weeks. RNA was purified from FACS sorted cell populations (live cells only) obtained from gonadal/epididymal adipose tissue depots. ATMs were defined as CD11c+ (CD45+CD64+ CD11c+) or CD11c- (CD45+CD64+ CD11c-) ATMs. ATDC were defined as CD64- CD11c+. PA were defined as CD31- CD45- Sca1+ PDGFRA+.
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