| Title: | Genetically Determined Loss-of-Function of the Organic Cation Transporter OCT1 Is Associated with Lower Liver Fat Content in Humans |
| Journal: | International Journal of Molecular Sciences |
| Published: | 19 Aug 2026 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/42653422/ |
| DOI: | https://doi.org/10.3390/ijms27167422 |
| URL: | http://dx.doi.org/10.3390/ijms27167422 |
Publication 20965
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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 (p = 0.027 in SHIP; p = 2.9 × 10-6 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.</p>
11 Keywords
- Aged
- Animals
- Fatty Liver
- Female
- Humans
- Liver
- Magnetic Resonance Imaging
- Male
- Middle Aged
- Octamer Transcription Factor-1
- Organic Cation Transporter 1
12 Authors
- Anna K. Scheurer-Böhme
- Eileen Moritz
- Stefan Weiss
- Robin Bülow
- Marie-Luise Kromrey
- M. Kamal Nasr
- Uwe Völker
- Henry Völzke
- Stefan Engeli
- Jens-Peter Kühn
- Alexander Teumer
- Mladen V. Tzvetkov
1 Application
| Application ID | Title |
|---|---|
| 319358 | Impact of naturally occurring genetic variations in hepatic transporters on cholesterol and glucose homeostasis, fatty liver, cardiovascular health, and lifespan. |
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