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Short-term variability of the human serum metabolome depending on nutritional and metabolic health status.

ABSTRACT: The intra-individual variability of the human serum metabolome over a period of 4 weeks and its dependence on metabolic health and nutritional status was investigated in a single-center study under tightly controlled conditions in healthy controls, pre-diabetic individuals and patients with type-2 diabetes mellitus (T2DM, n?=?10 each). Untargeted metabolomics in serum samples taken at three different days after overnight fasts and following intake of a standardized mixed meal showed that the human serum metabolome is remarkably stable: The median intra-class correlation coefficient (ICC) across all metabolites and all study participants was determined as 0.65. ICCs were similar for the three different health groups, before and after meal intake, and for different metabolic pathways. Only 147 out of 1438 metabolites (10%) had an ICC below 0.4 indicating poor stability over time. In addition, we confirmed previously identified metabolic signatures differentiating healthy, pre-diabetic and diabetic individuals. To our knowledge, this is the most comprehensive study investigating the temporal variability of the human serum metabolome under such tightly controlled conditions.

SUBMITTER: Agueusop I

PROVIDER: S-EPMC7530737 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Short-term variability of the human serum metabolome depending on nutritional and metabolic health status.

Agueusop Inoncent I Musholt Petra B PB Klaus Beate B Hightower Kendra K Kannt Aimo A

Scientific reports 20201001 1

The intra-individual variability of the human serum metabolome over a period of 4 weeks and its dependence on metabolic health and nutritional status was investigated in a single-center study under tightly controlled conditions in healthy controls, pre-diabetic individuals and patients with type-2 diabetes mellitus (T2DM, n = 10 each). Untargeted metabolomics in serum samples taken at three different days after overnight fasts and following intake of a standardized mixed meal showed that the hum ...[more]

PMID: 33004816

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Project description:Transcriptomics and functional bioinformatics were used to investigate the potential interactions of undernutrition and the presence of the conceptus at the time of maternal recognition of pregnancy on uterine indicators of metabolism and reproduction. Adult Rasa Aragonesa ewes were allocated to one of two planes of nutrition during 28 days: maintenance energy intake (control; 5 cyclic, 6 pregnant ewes) providing 7.8 MJ of metabolisable energy per ewe and 0.5 maintenance intake (undernourished; 6 cyclic, 7 pregnant ewes) providing 3.9 MJ of metabolisable energy per ewe. RNA from uterine tissue was harvested at slaughter on day 14 of estrus or pregnancy, and hybridized to the Agilent 15K Sheep Microarray chip. Functional bioinformatics analyses were performed using the Dynamic Impact Approach (DIA) and Ingenuity Pathway Analysis. Among metabolic pathways, citrate cycle, oxidative phosphorylation, pentose and glucuronate interconversions and biosynthesis of unsaturated fatty acids were upregulated in control pregnant compared with control cyclic ewes. However, these pathways were not altered in undernourished ewes. The presence of an embryo in undernourished ewes upregulated fatty acid and glycogenic amino acid metabolism. RIG-I and Toll like receptors and chemokine signaling pathways were upregulated by the presence of the embryo in both control and undernourished ewes, but in the latter group the impact was lower. Undernutrition alone upregulated carbohydrate metabolism, but different pathways were altered in cyclic versus pregnant ewes. Citrate cycle, glycolysis/gluconeogenesis, and pentose and glucuronate interconversions were upregulated in undernourished cyclic compared with control cyclic ewes. Glycolysis/gluconeogenesis, pyruvate and propanoate metabolism, beta-alanine and phenylalanine metabolism were upregulated in undernourished pregnant compared with control pregnant ewes, whereas biosynthesis of unsaturated fatty acids and replication and repair were downregulated. Undernutrition alone led to an overall weak activation of immune system pathways both in cyclic and pregnant ewes. However, undernourished cyclic compared with control cyclic ewes had a high activation of NOD-like and RIG-1 like receptor signaling pathways, whereas undernourished pregnant compared with control pregnant ewes only had a weak upregulation of T cell receptor signaling pathways. Overall, data revealed that metabolic and immune adaptations of the uterus to nutrient restriction are dependent on the presence of the conceptus.

Project description:BackgroundIncreased body mass index (BMI) is associated with better survival in patients with acute heart failure (AHF), which is a paradoxical phenomenon. However, it is unclear whether different nutritional status affects this association.Methods1325 patients with AHF from the Medical Information Mart for Intensive Care III database were retrospectively included. Nutritional status was assessed by serum albumin (SA) and prognostic nutritional index (PNI). Patients were divided into High-SA (≥ 3.5 g/dL) and Low-SA groups (< 3.5 g/dL), and they also were divided into High-PNI (≥ 38) and Low-PNI groups (< 38). Propensity-score matching (PSM) was used to control for the effect of baseline confounding factors, multifactor regression model was adopted to assess the association of nutritional status, BMI, and outcomes in AHF patients.ResultsOf the 1325 patients (mean age 72.4 ± 13.1 years), 52.1% (n = 690) were male, 13.1% (n = 173) died in hospital and 23.5% (n = 311) died within 90 days. Before PSM, after adjusting for potential confounders, in the High-SA population, compared with the under/normal BMI group, overweight and obesity were negatively correlated with 90-day mortality, with adjusted hazard ratios (HR) of 0.47, 95% confidence interval (CI) (0.30-0.74), P = 0.001; HR 0.45, 95%CI (0.28-0.72), P = 0.001, respectively. However, this correlation was much attenuated in the Low-SA group (overweight BMI: HR 1.06, 95%CI 0.75-1.50, P = 0.744; obese BMI: HR 0.86, 95%CI 0.59-1.24, P = 0.413). After PSM, those who were overweight or obese in the High-SA group had a 50-58% reduction in 90-day risk of death, while the protective effect disappeared in the Low-SA group (HR 1.09, 95% CI 0.70-1.71; HR 1.02, 95%CI 0.66 - 0.59). Similarly, results were similar in analyses using PNI as a nutritional assessment criterion.ConclusionOverweight or Obesity was associated with lower short-term mortality in well-nourished AHF patients, whereas this association was significantly attenuated or even disappeared in malnourished patients. Therefore, further research is needed for weight loss recommendations for malnourished obese patients with AHF.

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Short-term variability of the human serum metabolome depending on nutritional and metabolic health status.

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Short-term variability of the human serum metabolome depending on nutritional and metabolic health status.

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