MASLD, Mild Inflammatory Context, NAFLD
Conditions
Keywords
ex vivo, lipid metabolism, inflammation, hepatocytes, oxidative stress, plant extract, polyphenols, dietary/food supplement
Brief summary
Dietary intakes of saturated fatty acids remain well above nutritional recommendations for most European countries. This may progressively lead to a pro-inflammatory context and the alteration of lipid metabolism in the liver. The hypothesis of this study is that TOTUM-448 promotes the normal function of hepatocytes in a mild inflammatory context. To determine the cellular and molecular effects of TOTUM-448, circulating bioactive molecules after TOTUM-448 intake will be collected and then studied in human hepatocytes using an innovative ex vivo clinical approach developed by Clinic'n'Cell.
Interventions
DIETARY_SUPPLEMENTTOTUM-448
The study is divided in two phases. The first clinical phase of the project is aimed at determining TOTUM-448's metabolites absorption peak (two galenic forms will be tested: capsules and powder). Then, human circulating metabolites from polyphenols will be quantified and characterized by ultra-high performance liquid chromatography hyphenated with tandem mass spectrometry (UPLC-MS/MS). Once the absorption profile is characterized, volunteers will visit once again the clinical center for the collection of serum fractions either naïve (before ingestion) or enriched (containing circulating metabolites following TOTUM-448 ingestion). The enriched fraction (circulating bioactive collection) will be collected at t-max as characterized in the first phase (absorption profil's peak). Finally, biological activity of TOTUM-448 on human hepatocytes will be studied by comparing naïve serum and serum containing circulating metabolites according to an in vitro protocol.
Sponsors
Clinic'n'Cell
University Hospital, Clermont-Ferrand
Valbiotis
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Intervention model description
An ex vivo clinical approach.
Eligibility
Sex/Gender
MALE
Age
18 Years to 35 Years
Healthy volunteers
Yes
Inclusion criteria
Main Inclusion Criteria: * Lipid profile within reference values * Glycemia \< 100mg/dL * Normal hepatic function * Normal blood formulation * Normal renal function * BMI between 20 and 28kg/m2 * Non smoker or occasional smoker Main
Exclusion criteria
* All types of vaccination within one month * Alcohol intakes superior to World Health Organization recommendations * Ongoing pharmacological, dietary supplement and/or probiotic treatment * Consumption of enriched functional foods or dietary supplements within two weeks of inclusion * Any known disease * Allergy to ingredients of the study product * With dietary habits incompatible with the study conduct
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Evaluate the influence of circulating bioactive metabolites in blood stream resulting from the intake of TOTUM-448 on viability of human hepatocytes in a hyperlipidic pro-inflammatory context. | At phenolic compounds t-max obtained during kinetic phase. Note: According to previous studies, t-max is expected around 60 minutes. | Naïve will be compared to enriched serum from the 10 healthy participants at the previously determined t-max. |
| Evaluate the influence of circulating bioactive metabolites in blood stream resulting from the intake of TOTUM-448 on cholesterol storage of human hepatocytes in a hyperlipidic pro-inflammatory context. | At phenolic compounds t-max obtained during kinetic phase. Note: According to previous studies, t-max is expected around 60 minutes. | Naïve will be compared to enriched serum from the 10 healthy participants at the previously determined t-max. |
| Evaluate the influence of circulating bioactive metabolites in blood stream resulting from the intake of TOTUM-448 on triglyceride storage of human hepatocytes in a hyperlipidic pro-inflammatory context. | At phenolic compounds t-max obtained during kinetic phase. Note: According to previous studies, t-max is expected around 60 minutes. | Naïve will be compared to enriched serum from the 10 healthy participants at the previously determined t-max. |
| Evaluate the influence of circulating bioactive metabolites in blood stream resulting from the intake of TOTUM-448 on oxidative stress status of human hepatocytes in a hyperlipidic pro-inflammatory context. | At phenolic compounds t-max obtained during kinetic phase. Note: According to previous studies, t-max is expected around 60 minutes. | Naïve will be compared to enriched serum from the 10 healthy participants at the previously determined t-max. |
| Evaluate the influence of circulating bioactive metabolites in blood stream resulting from the intake of TOTUM-448 on pro-inflammatory cytokine expression of human hepatocytes in a hyperlipidic pro-inflammatory context. | At phenolic compounds t-max obtained during kinetic phase. Note: According to previous studies, t-max is expected around 60 minutes. | Naïve will be compared to enriched serum from the 10 healthy participants at the previously determined t-max. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to reach the maximum concentration in serum of detectable polyphenol metabolite concentrations by UPLC-MS/MS. | From timepoint 0 minute to timepoint 240 minutes. | After ingestion of TOTUM-448 the concentration in serum of detectable polyphenol metabolites will be assessed every 20 minutes during 240 minutes. |
Countries
France
Outcome results
None listed