Dataset Information

Arterio-venous metabolomics exploration reveals major changes across liver and intestine in the obese Yucatan minipig.

ABSTRACT: Blood circulation mainly aims at distributing the nutrients required for tissue metabolism and collecting safely the by-products of all tissues to be further metabolized or eliminated. The simultaneous study of arterial (A) and venous (V) specific metabolites therefore has appeared to be a more relevant approach to understand and study the metabolism of a given organ. We propose to implement this approach by applying a metabolomics (NMR) strategy on paired AV blood across the intestine and liver on high fat/high sugar (HFHS)-fed minipigs. Our objective was to unravel kinetically and sequentially the metabolic adaptations to early obesity/insulin resistance onset specifically on these two tissues. After two months of HFHS feeding our study of AV ratios of the metabolome highlighted three major features. First, the hepatic metabolism switched from carbohydrate to lipid utilization. Second, the energy demand of the intestine increased, resulting in an enhanced uptake of glutamine, glutamate, and the recruitment of novel energy substrates (choline and creatine). Third, the uptake of methionine and threonine was considered to be driven by an increased intestine turnover to cope with the new high-density diet. Finally, the unique combination of experimental data and modelling predictions suggested that HFHS feeding was associated with changes in tryptophan metabolism and fatty acid ?-oxidation, which may play an important role in lipid hepatic accumulation and insulin sensitivity.

SUBMITTER: Poupin N

PROVIDER: S-EPMC6715693 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Arterio-venous metabolomics exploration reveals major changes across liver and intestine in the obese Yucatan minipig.

Poupin Nathalie N Tremblay-Franco Marie M Amiel Aurélien A Canlet Cécile C Rémond Didier D Debrauwer Laurent L Dardevet Dominique D Thiele Ines I Aurich Maike K MK Jourdan Fabien F Savary-Auzeloux Isabelle I Polakof Sergio S

Scientific reports 20190829 1

Blood circulation mainly aims at distributing the nutrients required for tissue metabolism and collecting safely the by-products of all tissues to be further metabolized or eliminated. The simultaneous study of arterial (A) and venous (V) specific metabolites therefore has appeared to be a more relevant approach to understand and study the metabolism of a given organ. We propose to implement this approach by applying a metabolomics (NMR) strategy on paired AV blood across the intestine and liver ...[more]

PMID: 31467335

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Project description:Point-of-care ultrasonography (POCUS) with concomitant venous and arterial Doppler assessment enables clinicians to assess organ-specific blood supply. To date, no studies have investigated the usefulness of including a comprehensive perioperative POCUS assessment of patients undergoing major laparoscopic surgery. The primary aim of the present study was to evaluate whether the combined venous and arterial renal flow evaluation, measured at different time points of perioperative period, may represent a clinically useful non-invasive method to predict postoperative acute kidney injury (AKI) after major laparoscopic urologic surgery. The secondary outcome was represented by the development of any postoperative complication at day 7. We included 173 patients, subsequently divided for analysis depending on whether they did (n = 55) or did not (n = 118) develop postoperative AKI or any complications within the first 7 days. The main results of the present study were that: (1) the combination of arterial hypoperfusion and moderate-to-severe venous congestion inferred by POCUS were associated with worst outcomes (respectively, HR: 2.993, 95% CI: 1.522-5.884 and HR: 8.124, 95% CI: 3.542-18, p < 0.001); (2) high intra-operative abdominal pressure represents the only independent determinant of postoperative severe venous congestion (OR: 1.354, 95% CI: 1.017-1.804, p = 0.038); (3) the overall number of complications relies on the balance between arterial inflow and venous outflow in order to ensure the adequacy of peripheral perfusion; and (4) the overall reliability of splanchnic perfusion assessment by Doppler is high with a strong inter-rater reliability (ICC: 0.844, 95% CI: 0.792-0.844). The concomitant assessment of arterial and venous Doppler patterns predicts postoperative complications after major laparoscopic urologic surgery and may be considered a useful ultrasonographic biomarker to stratify vulnerable patients at risk for development of postoperative complications.

Project description:Objectives: We have previously identified a population of cells that expressed stemness-associated markers in extracranial arterio-venous malformation (AVM) and demonstrated expression of cathepsins B, D, and G on embryonic stem cell (ESC)-like populations in other vascular anomalies. This study investigated the expression of cathepsins B, D, and G, and their localization in relation to this primitive population in extracranial AVM. Methods: Immunohistochemical staining was performed on AVM tissue samples from 13 patients to demonstrate expression of cathepsins B, D, and G. Western blotting was performed on four AVM tissue samples and three AVM-derived primary cell lines to confirm protein expression of cathepsins B and D proteins. RT-qPCR was performed on three AVM-derived primary cell lines to demonstrate transcript expression of cathepsins B, D, and G. Enzymatic activity assays were performed on three AVM-derived primary cell lines to investigate if cathepsins B and D were active. Localization of the cathepsins was investigated using immunofluorescence dual-staining of the cathepsins with the ESC markers OCT4 and SOX2, and mast cells marker chymase on two of the 13 AVM tissue samples. Results: Immunohistochemical staining demonstrated expression of cathepsins B, D, and G in all 13 AVM tissue samples. Western blotting showed expression of cathepsins B and D proteins in all four AVM tissue samples and all three AVM-derived primary cell lines. RT-qPCR demonstrated transcripts of cathepsins B, D, and G in all three AVM-derived primary cell lines. Enzymatic activity assays showed that cathepsins B and D were active. Immunofluorescence staining showed expression of cathepsins B and D on the OCT4+/SOX2+ endothelium and media of the lesional vessels and cells within the stroma in AVM nidus. Cathepsin G was expressed on the chymase+ phenotypic mast cells. Conclusions: This study demonstrated the novel finding of the expression of cathepsins B, D, and G in AVM. Cathepsins B and D were expressed by the primitive population, and cathepsin G was localized to mast cells, within the AVM nidus.

Dataset Information

Arterio-venous metabolomics exploration reveals major changes across liver and intestine in the obese Yucatan minipig.

Publications

Arterio-venous metabolomics exploration reveals major changes across liver and intestine in the obese Yucatan minipig.

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