Dataset Information

Different Metabolic Pathways Associated With Total Cortisol Exposure and the Cortisol Time Profile: A Randomized Crossover Trial

ABSTRACT:

Excess cortisol exposure and disruption of the circadian cortisol profile are both associated with adverse clinical outcomes. The aim of this study was to identify unique metabolites and metabolic pathways associated with total cortisol exposure and/or variation of the cortisol time profile. Eighteen adults with primary adrenal insufficiency (AI) received the same daily dose of hydrocortisone (HC) administered as a once-daily (OD) dual-release tablet and conventional HC tablets 3 times daily (TID) in a randomized, 12-week, cross-over trial. Serum and urine samples were collected during 24 h in-house standardized pharmacokinetic sampling days and metabolites were detected using liquid and gas chromatography-mass spectrometry (LC-MS and GC-MS). Total cortisol exposure was calculated by the area under the serum cortisol concentration-time curve and variability of the cortisol time profile was quantified by calculating the lag–1 autocorrelation from serum cortisol concentrations over 24 hours. During TID administration, total cortisol exposure was 20% higher and the cortisol time profile variability was larger, compared to OD administration. In total, 2406 metabolites were detected. Serum metabolites uniquely correlated with total cortisol exposure were involved in arginine biosynthesis, and alanine-aspartate-glutamate and tryptophan metabolism. Serum metabolites uniquely correlated with the cortisol time profile variability were involved in primary bile acid biosynthesis and cysteine-methionine metabolism. We identified different groups of metabolites and metabolic pathways that specifically correlate with total exposure and time profile variability of serum cortisol. These findings suggest that total cortisol exposure and the time profile of serum cortisol have independent metabolic and regulatory effects in the human body.

INSTRUMENT(S): Liquid Chromatography MS - negative - reverse phase, Liquid Chromatography MS - positive - reverse phase, Gas Chromatography MS - positive

PROVIDER: MTBLS13147 | MetaboLights | 2026-01-16

REPOSITORIES: MetaboLights

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	a_MTBLS13147_Serum_GC-MS_positive__metabolite_profiling.txt	Txt
	a_MTBLS13147_Serum_LC-MS_negative_reverse-phase_metabolite_profiling.txt	Txt
	a_MTBLS13147_Serum_LC-MS_positive_reverse-phase_metabolite_profiling.txt	Txt
	a_MTBLS13147_Urine_LC-MS_negative_reverse-phase_metabolite_profiling.txt	Txt
	a_MTBLS13147_Urine_LC-MS_positive_reverse-phase_metabolite_profiling.txt	Txt

Items per page:

1 - 5 of 12

Similar Datasets

Project description:Cushing’s syndrome is one of the most common endocrinopathies in adult dogs. It is a consequence of chronic hypercortisolemia (HC), that may present a pathological or iatrogenic origin. Among other alterations, Cushing’s syndrome involves the differential modulation of lipid metabolism, i.e., while enhanced lipolysis is observed in subcutaneous adipose tissue, an increased accumulation is observed in visceral adipose tissue (VAT). VAT acts in a variety of mechanisms besides energy storage, playing an important role as an endocrine organ. Strikingly, the effects of HC in VAT were never investigated in the dog. Thus, in the present project the transcriptome of visceral adipose tissue (VAT) of dogs sampled before and after long-term HC was investigated. HC was induced by subcutaneously implanted ACTH-releasing pumps and canine VAT was collected before and after treatment, followed by deep RNA sequencing (RNA-Seq) analysis. A total of 1190 differentially expressed genes (DEG) were found in response to ACTH treatment (P and FDR < 0.01). Genes upregulated post-ACTH were mostly associated with translation; in contrast, terms enriched in downregulated DEGs were related to cell adhesion and migration, intracellular signaling, immune response, extracellular matrix and angiogenesis. Transcript counts of HSD11B2, enzyme responsible for the conversion of active cortisol into cortisone, and of the glucocorticoid receptor, were decreased after ACTH treatment, while HSD11B1, activator of cortisol, were increased. Furthermore, treatment further appeared to modulate insulin signaling, hormonal sensitivity, cell proliferation, extracellular matrix organization, lipolysis, vasculogenesis and immune signaling. These results allowed the identification of factors that might play an important role in HC-related expansion of VAT, e.g., TIMP4, FGF1, CCR2, CXCR4 and HSD11B1/2. Similarities in the effects of chronic hypercortisolemia on VAT of dogs and humans were further highlighted.

Project description:Objectives: Hashimoto’s thyroiditis (HT) is one of the most common autoimmune disorders; however, its underlying pathological mechanisms remain unclear. Although aberrant glycosylation has been implicated in the N-glycome of immunoglobulin G (IgG), changes in serum proteins have not been comprehensively characterized. This study aimed to investigate the glycosylation profile of serum samples of HT patients that were depleted of highly abundant proteins by and propose the potential functions of glycoproteins for the further study of pathological mechanisms of HT . Methods: A lectin microarray containing 70 lectins was used to detect and analyze glycosylation of serum proteins using serum samples (N=27 HT; N=26 healthy control [HC]) depleted of abundant proteins. Significant differences in glycosylation status between HT patients and the HC group were verified by lectin blot analysis. A lectin-based pull-down assay combined with mass spectrometry was used to investigate potential glycoproteins combined with differentially present lectins, and an enzyme-linked immunosorbent assay (ELISA) was used to identify the expression of targeted glycoproteins in 131 patients with papillary thyroid carcinoma (PTC), 131 patients with benign thyroid nodules (BTN) patients, 130 patients with HT, and 128 HCs. Results: Compared with the HC group, the majority of the lectin binding signals in HT group were weakened, while the Vicia villosa agglutinin (VVA) binding signal was increased. The difference in VVA binding signals verified by lectin blotting was consistent with the results of the lectin microarray. A total of 113 potential VVA-binding glycoproteins were identified by mass spectrometry and classified by gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) analyses . Using ELISA, we confirmed that lactoferrin (LTF) and mannan-binding lectin-associated serine protease 1 (MASP-1) levels were elevated in the serum of patients with HT and PTC. Conclusions: Following depletion of abundant proteins, remaining serum proteins in HT patients exhibited lower glycosylation levels than those observed in HCs. An increased level of potential VVA-binding glycoproteins may play an important role in HT development. LTF and MASP-1 expression was significantly higher in the serum of HT and PTC patients, suggesting key roles played by glycosylation in pathological mechanisms underlying HT and PTC.

Dataset Information

Different Metabolic Pathways Associated With Total Cortisol Exposure and the Cortisol Time Profile: A Randomized Crossover Trial

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets