Implementation and Validation of an Analytical Protocol for Measuring de Novo Lipogenesis in the Liver Using Stable Isotopes

KU Leuven10 enrolled

Overview

During this study, an analytical protocol for measuring hepatic de novo lipogenesis (DNL) using deuterium oxide (²H₂O) will be implemented and validated in healthy participants.

This study will implement and validate an analytical approach for measuring fractional hepatic de novo lipogenesis (DNL) in healthy adults using deuterium oxide (²H₂O). Participants will consume ²H₂O according to the study schedule. Following oral administration, ²H₂O enters and enriches the body-water pool, providing a source of deuterium (²H) for incorporation into palmitate newly synthesized by the liver and subsequently exported in VLDL-triglycerides. Fasting blood samples will be collected at predefined time points throughout the study. These samples will be used to determine fractional hepatic DNL and characterize the washout of ²H₂O from the body.

Study Type

INTERVENTIONAL

Allocation

Purpose

BASIC_SCIENCE

Masking

NONE

Enrollment

Conditions

De Novo Lipogenesis (DNL)Lipid Metabolism Stable Isotope Tracing Healthy Volunteers (HV)

Interventions

Deuterium oxideOTHER

Participants will orally consume 70% deuterium oxide (²H₂O), a non-radioactive stable isotope tracer, for 10 consecutive days. The total daily amount will be 100 mL on Days 1-4 and 50 mL on Days 5-10. The tracer will be used to label body water and newly synthesized palmitate for the measurement of fractional hepatic de novo lipogenesis and plasma-water ²H₂O washout.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 60 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Healthy male or female individuals. * Age between 18-60 years old with a body mass index (BMI) between 18.5 and 25 kg/m². * Willingness to consume ²H₂O as part of the study protocol. Exclusion Criteria: Participants will be excluded from the study based on self-reported health status if they meet any of the following conditions: * Chronic diseases (e.g., diabetes, MASLD, hypertension, cardiovascular diseases) and/or chronic consumption of medication (e.g., antihypertensive drugs, diabetes medications, lipid-lowering agents, immunomodulatory drugs, or other prescribed medications for long-term management of health conditions). * History of blood donation within the past 3 months. * Vaccination within the past 4 weeks. * Pregnancy or breastfeeding. * Participation in another clinical study.

Locations (1)

KU Leuven/ UZ Leuven

Leuven, Vlaams-Brabant, Belgium

Outcomes

Primary Outcomes

Fractional hepatic de novo lipogenesis

VLDL will be isolated from fasting plasma by ultracentrifugation. Fractional hepatic de novo lipogenesis will be calculated from the ²H enrichment of VLDL-TG palmitate, normalized to plasma-water ²H enrichment and the effective number of exchangeable hydrogen positions in palmitate (n = 22), and will be expressed as a percentage (%).

Time frame: Day 11

Secondary Outcomes

Plasma-water ²H enrichment

Plasma-water ²H enrichment will be measured at baseline, on Day 11, and at follow-up visits during the washout period to determine the time required for ²H enrichment to return close to baseline.

Time frame: Baseline; Day 11; and at 4, 6, and 8 weeks following completion of the 10-day ²H₂O intake period.

Data from ClinicalTrials.gov

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