Selenium deficiency fastens intestinal barrier dysfunction and inflammation during high-fat/high-fructose-induced MASLD development in male mice.

The chronic metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by hepatic accumulation of lipids, which results in gradually progressing loss of liver function with concomitant oxidative stress and hepatic inflammation. While effects of the macronutrient intake have been widely studied, less is known about the contribution of micronutrients to MASLD development. The trace element selenium is of particular interest as it is highly abundant in the liver, is incorporated into antioxidant selenoproteins, and supports the immune response, thus targeting key aspects of MASLD pathogenesis. In the European population, the selenium intake is usually suboptimal meaning that not all selenoproteins are fully expressed. Accordingly, we asked the question if a selenium-deficient diet would have an impact on the development and severity of high-fat/high-fructose (Hf/Hf)-induced MASLD in mice. Male C57BL/6Jrj mice were fed a Hf/Hf diet for 8, 12, 16, and 24 weeks, which either contained adequate or deficient amounts of selenium. Even though the selenium deficiency substantially reduced expression of selenoproteins, we observed overall only moderate changes on liver parameters. During the development of MASLD, selenium deficiency increased hepatic inflammation, which however, was not detectable after 24 weeks anymore. Intestinal barrier integrity was reduced in the selenium-deficient group, which might have contributed to the observed pro-inflammatory effect in the liver. Overall, suboptimal selenium levels appear to accelerate the progression of MASLD in its early stages, particularly because of elevated inflammation. Thus, adequate selenium intake might be specifically important in early-stage MASLD patients with suboptimal selenium status to slow disease progression.