Vitamin E sequestration in MASLD and effect of supplementation in mitigating progression to MASH

Authors

• TD Greene
• S Teng
• I Rozga
• R Berman
• N Munyan
• I Ebenuwa
• M Levine
• PC Violet

Abstract

The global obesity epidemic has severe implications for human health, particularly the rise of metabolic dysfunction-associated steatotic liver disease (MASLD), leading cause of chronic liver disease. Studies have implicated dysregulation of the fat-soluble antioxidant vitamin E in pathogenesis of fatty liver disease. We hypothesized excess body fat sequesters vitamin E resulting in local deficiency and exacerbating metabolic dysfunction, which may be mitigated by supplementation. We conducted pharmacokinetics studies in 6 obese women with MASLD and 10 healthy controls, using vitamin E labeled stable isotopes. MASLD cohort had significantly reduced vitamin E bioavailability that correlated with liver fat, suggesting a fat-mediated vitamin E sequestration. To investigate mitigative effect of vitamin E supplementation, we used a mouse model of MASLD fed a regular diet or a western diet (high fat/high sugar) with 500 IU/Kg or <25 IU/Kg of vitamin E. We monitored mouse weights and assessed metabolic parameters using calorimetric chambers. Liver, liver fat and vitamin E levels were also measured. Mice on a high-fat diet with high vitamin E gained less weight, had increased hepatic and plasma vitamin E levels, decreased oxygen consumption, and lower fat mass compared to those on the same diet with low vitamin E. Furthermore, mice fed with high E had a lower grade of steatohepatitis, assessed by histopathology. Findings suggest potential preventative role of vitamin E supplementation in MASLD.

Scientific Focus Area: Clinical Research

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