Circulating Human Metabolites Resulting from TOTUM-070 Absorption (a Plant-Based, Polyphenol-Rich Ingredient) Improve Lipid Metabolism in Human Hepatocytes: Lessons from an Original Ex Vivo Clinical Trial
| dc.rights.license | open | en_US |
| dc.contributor.author | WAUQUIER, Fabien | |
| dc.contributor.author | BOUTIN-WITTRANT, Line | |
| hal.structure.identifier | Unité de Recherche Œnologie [Villenave d'Ornon] [OENO] | |
| dc.contributor.author | KRISA, Stéphanie | |
| hal.structure.identifier | Unité de Recherche Œnologie [Villenave d'Ornon] [OENO] | |
| hal.structure.identifier | Plateforme Bordeaux Metabolome | |
| dc.contributor.author | VALLS FONAYET, Josep | |
| dc.contributor.author | LANGHI, Cédric | |
| dc.contributor.author | OTERO, Yolanda F. | |
| dc.contributor.author | SIRVENT, Pascal | |
| dc.contributor.author | PELTIER, Sébastien | |
| dc.contributor.author | BARGETTO, Maxime | |
| dc.contributor.author | CAZAUBIEL, Murielle | |
| dc.contributor.author | SAPONE, Véronique | |
| dc.contributor.author | BOUCHARD-MERCIER, Annie | |
| dc.contributor.author | ROUX, Véronique | |
| dc.contributor.author | MACIAN, Nicolas | |
| dc.contributor.author | PICKERING, Gisèle | |
| dc.contributor.author | WITTRANT, Yohann | |
| dc.date.accessioned | 2024-04-18T14:56:05Z | |
| dc.date.available | 2024-04-18T14:56:05Z | |
| dc.date.issued | 2023 | |
| dc.identifier.issn | 2072-6643 | en_US |
| dc.identifier.uri | https://oskar-bordeaux.fr/handle/20.500.12278/199227 | |
| dc.description.abstractEn | TOTUM-070 is a patented polyphenol-rich blend of five different plant extracts showing separately a latent effect on lipid metabolism and potential synergistic properties. In this study, we investigated the health benefit of such a formula. Using a preclinical model of high fat diet, TOTUM-070 (3 g/kg of body weight) limited the HFD-induced hyperlipemia with a reduction in triglyceride (−32% after 6 weeks; −20.3% after 12 weeks) and non-HDL cholesterol levels (−21% after 6 weeks; −38.4% after 12 weeks). To further investigate such a benefit and its underlying mechanisms in humans, we designed an ex vivo clinical approach to collect the circulating bioactives resulting from TOTUM-070 ingestion and to determine their biological activities on human hepatocytes. Human serum was obtained from healthy subjects before and after intake of TOTUM-070 (4995 mg). The presence of circulating metabolites was assessed by UPLC-MS/MS. Serum containing metabolites was further incubated with hepatocytes cultured in a lipotoxic environment (palmitate, 250 µM). RNA sequencing analyses show that lipid metabolism was one of the most impacted processes. Using histologic, proteomic, and enzymatic assays, the effects of human TOTUM-070 bioactives on hepatocyte metabolism were characterized by (1) the inhibition of lipid storage, including both (2) triglycerides (−41%, p < 0.001) and (3) cholesterol (−50%, p < 0.001) intracellular content, (4) a reduced de novo cholesterol synthesis (HMG-CoA reductase activity −44%, p < 0.001), and (5) a lowered fatty acid synthase protein level (p < 0.001). Altogether, these data support the beneficial impact of TOTUM-070 on lipid metabolism and provide new biochemical insights in human mechanisms occurring in liver cells. © 2023 by the authors. | |
| dc.language.iso | EN | en_US |
| dc.rights | Attribution 3.0 United States | * |
| dc.rights.uri | http://creativecommons.org/licenses/by/3.0/us/ | * |
| dc.subject.en | Clinical trial | |
| dc.subject.en | Ex vivo | |
| dc.subject.en | Lipid metabolism | |
| dc.subject.en | Cholesterol | |
| dc.subject.en | Hepatocytes | |
| dc.title.en | Circulating Human Metabolites Resulting from TOTUM-070 Absorption (a Plant-Based, Polyphenol-Rich Ingredient) Improve Lipid Metabolism in Human Hepatocytes: Lessons from an Original Ex Vivo Clinical Trial | |
| dc.type | Article de revue | en_US |
| dc.identifier.doi | 10.3390/nu15081903 | en_US |
| dc.subject.hal | Sciences du Vivant [q-bio]/Biologie végétale | en_US |
| bordeaux.journal | Nutrients | en_US |
| bordeaux.volume | 15 | en_US |
| bordeaux.hal.laboratories | Oenologie - UMR 1366 | en_US |
| bordeaux.issue | 8 | en_US |
| bordeaux.institution | Université de Bordeaux | en_US |
| bordeaux.institution | Bordeaux INP | en_US |
| bordeaux.institution | INRAE | en_US |
| bordeaux.peerReviewed | oui | en_US |
| bordeaux.inpress | non | en_US |
| hal.popular | non | en_US |
| hal.audience | Internationale | en_US |
| hal.export | false | |
| dc.rights.cc | CC BY | en_US |
| bordeaux.COinS | ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Nutrients&rft.date=2023&rft.volume=15&rft.issue=8&rft.eissn=2072-6643&rft.issn=2072-6643&rft.au=WAUQUIER,%20Fabien&BOUTIN-WITTRANT,%20Line&KRISA,%20St%C3%A9phanie&VALLS%20FONAYET,%20Josep&LANGHI,%20C%C3%A9dric&rft.genre=article |
