Vitamin B1NEW2026-08

Genetically Determined Loss-of-Function of the Organic Cation Transporter OCT1 Is Associated with Lower Liver Fat Content in Humans.

Scheurer-Böhme Anna K, Moritz Eileen, Weiss Stefan, Bülow Robin et al. — International journal of molecular sciences

Summary

A recent study found that people with a specific genetic variation that reduces the function of a protein called OCT1 tend to have less fat in their liver. This protein helps transport vitamin B1, and its reduced function might alter how the liver processes energy, potentially leading to lower fat accumulation. This discovery offers new avenues for understanding and potentially addressing fatty liver disease.

AI-generated summary — read the original

Key points

A genetic variation that reduces the function of a protein called OCT1 is linked to lower fat levels in the human liver.
OCT1 is known to transport vitamin B1, suggesting a possible connection between vitamin B1 metabolism and liver fat.
This genetic difference appears to independently predict lower liver fat, even after accounting for other factors like BMI.
Understanding this link could help in developing new strategies to prevent or manage fatty liver disease.

What the study looked at

This research aimed to understand if genetic variations that reduce the function of a protein called OCT1 are linked to the amount of fat in the human liver. Previous animal studies suggested that OCT1, which helps transport vitamin B1, might play a role in liver fat accumulation. Researchers examined genetic information and liver fat measurements from two large groups of people. First, they analyzed data from over 2,500 participants in the Study of Health in Pomerania (SHIP), using whole-body MRI scans to measure liver fat. They then confirmed their findings using data from over 31,000 individuals in the UK Biobank. The study consistently showed that people with genetically reduced OCT1 function had lower liver fat content in both groups. This link held true even after considering other factors like age, BMI, alcohol consumption, and biological sex. Lab experiments further indicated that OCT1 might influence how cells process glucose for energy, potentially explaining its effect on liver fat.

Dietary takeaway

This study reveals a genetic link between OCT1 function and liver fat, hinting at a role for vitamin B1 transport in liver health. While vitamin B1 is essential for energy metabolism, this research doesn't directly suggest specific dietary changes. Until more studies confirm these findings, focusing on a balanced diet rich in whole grains, legumes, and lean meats remains the best approach for adequate vitamin B1 intake and overall health.

Abstract

Fatty liver is associated with increased all-cause mortality. Organic cation transporter 1 (OCT1) is a polyspecific hepatic uptake transporter. OCT1 mediates hepatic uptake of vitamin B1 (thiamine); thus, OCT1 deficiency may impair thiamine availability and consequently reduce glucose-derived energy. Consequently, OCT1-knockout mice exhibit significantly reduced liver fat. In 2% of Europeans and White Americans, common genetic variants markedly reduce OCT1 function. In this study, we used these naturally occurring variants to investigate the influences of reduced OCT1 function on liver fat in humans. We analyzed 2512 whole-body MRI datasets from the Study of Health in Pomerania (SHIP) and validated the findings using 31,594 datasets from the UK Biobank. In both cohorts, OCT1 deficiency was associated with lower fat content in the liver ( = 0.027 in SHIP; = 2.9 × 10 in the UK Biobank), but not in other body compartments. OCT1 deficiency remained an independent predictor after adjustment for age, BMI, daily alcohol consumption, and biological sex. To investigate underlying mechanisms, we used Seahorse assays to show that OCT1-overexpressing cells exhibited increased mitochondrial metabolic activity when glucose was the sole energy source. Our findings warrant further investigation of OCT1 as a potential contributor to the pathogenesis of fatty liver.

View on PubMed →DOI: 10.3390/ijms27167422