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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. | LitMetric

AI Article Synopsis

  • - TOTUM-070 is a patented blend of five plant extracts that has shown potential in improving lipid metabolism and reducing fat-related health issues in a preclinical study with a high-fat diet, leading to significant decreases in triglyceride and non-HDL cholesterol levels over 12 weeks.
  • - The human study involved participants ingesting TOTUM-070, with subsequent analysis of blood samples showing the presence of beneficial metabolites that were tested on liver cells under lipotoxic conditions, revealing a strong impact on lipid metabolism.
  • - Key findings indicated that the bioactives from TOTUM-070 helped inhibit lipid storage in liver cells, significantly reducing triglyceride and cholesterol levels, while also lowering the activity of enzymes involved in cholesterol synthesis and fatty acid

Article Abstract

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%, < 0.001) and (3) cholesterol (-50%, < 0.001) intracellular content, (4) a reduced de novo cholesterol synthesis (HMG-CoA reductase activity -44%, < 0.001), and (5) a lowered fatty acid synthase protein level ( < 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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10145174PMC
http://dx.doi.org/10.3390/nu15081903DOI Listing

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