Vitamin E sequestration by liver fat in humans

Area of Science:

• Metabolic disorders
• Hepatology
• Nutritional science

Background:

• Obesity-associated hepatosteatosis is hypothesized to act as a reservoir for fat-soluble vitamins.
• Altered vitamin physiology may result from excess liver fat accumulation.

Purpose of the Study:

• To investigate if excess liver fat in women with obesity-associated hepatosteatosis sequesters alpha-tocopherol (vitamin E).
• To compare vitamin E pharmacokinetics and kinetics in women with and without hepatosteatosis.

Main Methods:

• Administered custom-synthesized deuterated alpha-tocopherols (d3- and d6-) to healthy women and women with hepatosteatosis.
• Utilized fluorescently labeled alpha-tocopherol for in vitro cell studies.
• Analyzed pharmacokinetics and kinetics parameters of vitamin E distribution and release.

Main Results:

• In healthy subjects, vitamin E rapidly distributed into lipoproteins and was processed by the liver.
• Subjects with hepatosteatosis showed similar liver uptake but significantly reduced vitamin E release rates.
• In vitro studies confirmed alpha-tocopherol localization within lipid droplets of fat-loaded hepatocytes.

Conclusions:

• Excess liver fat in hepatosteatosis dysregulates the liver's role in vitamin E metabolism.
• Hepatic sequestration of vitamin E by hepatosteatosis may contribute to liver disease progression.
• Hepatosteatosis might similarly affect the metabolism of other fat-soluble vitamins.