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
VALLS FONAYET, Josep
Unité de Recherche Œnologie [Villenave d'Ornon] [OENO]
Plateforme Bordeaux Metabolome
< Réduire
Unité de Recherche Œnologie [Villenave d'Ornon] [OENO]
Plateforme Bordeaux Metabolome
Langue
EN
Article de revue
Ce document a été publié dans
Nutrients. 2023, vol. 15, n° 8
Résumé en anglais
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 ...Lire la suite >
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.< Réduire
Mots clés en anglais
Clinical trial
Ex vivo
Lipid metabolism
Cholesterol
Hepatocytes
Unités de recherche