Selenoneine Ameliorates Hepatocellular Injury and Hepatic Steatosis in a Mouse Model of NAFLD

Abstract

Selenoneine is a novel organic selenium compound markedly found in the blood, muscles, and other tissues of fish. This study aimed to determine whether selenoneine attenuates hepatocellular injury and hepatic steatosis in a mouse model of non-alcoholic fatty liver disease (NAFLD). Mice lacking farnesoid X receptor (FXR) were used as a model for fatty liver disease, because they exhibited hepatomegaly, hepatic steatosis, and hepatic inflammation. Fxr-null mice were fed a 0.3 mg Se/kg selenoneine-containing diet for four months. Significant decreases in the levels of hepatomegaly, hepatic damage-associated diagnostic markers, hepatic triglycerides, and total bile acids were found in Fxr-null mice fed with a selenoneine-rich diet. Hepatic and blood clot total selenium concentrations were 1.7 and 1.9 times higher in the selenoneine group than in the control group. A marked accumulation of selenoneine was found in the liver and blood clot of the selenoneine group. The expression levels of oxidative stress-related genes (heme oxygenase 1 (Hmox1), glutathione S-transferase alpha 1 (Gsta1), and Gsta2), fatty acid synthetic genes (stearoyl CoA desaturase 1(Scd1) and acetyl-CoA carboxylase 1 (Acc1)), and selenoprotein (glutathione peroxidase 1 (Gpx1) and selenoprotein P (Selenop)) were significantly decreased in the selenoneine group. These results suggest that selenoneine attenuates hepatic steatosis and hepatocellular injury in an NAFLD mouse model.

The role of selenium in type-2 diabetes mellitus and its metabolic comorbidities

“…In particular, selenite is known to induce oxidative stress through redox cycling at high concentrations [ 136 ]; this may also explain its adverse effects on insulin signaling. Selenoneine, a novel organic Se compound occurring in fish, ameliorated hepatic steatosis and hepatocellular injury in a mouse model of NAFLD, despite decreased hepatic selenoprotein mRNA levels [ 13 , 137 ]. A novel non-canonical form of Se incorporation into proteins, named facultative protein selenation, has recently been discovered to occur at high Se-supplementation with SeMet; key metabolic proteins in the brown adipose tissue of mice were modified, and the animals were protected from obesity through enhanced thermogenesis [ 138 ].…”

High Concentration of Heavy Metal and Metalloid Levels in Edible Campomanesia adamantium Pulp from Anthropic Areas

“…Other studies have recommended 0.018 mg/day of Se quantity intake for children (4–6 y), 0.023 mg/day for adolescent males 10–18 y and 0.021 mg/day for adult females (19–65 y), 0.027 mg/day for males and 0.0204 mg/day [ 54 ]. The benefit of the consumption of Se is correlated with preventing and decreasing diabetes mellitus, cancers [ 55 ], improving male fertility [ 56 , 57 ], human neuropathies [ 58 ] and hepatic steatosis [ 59 ].…”

Selenoproteins Protect Against Avian Liver Necrosis by Metabolizing Peroxides and Regulating Receptor Interacting Serine Threonine Kinase 1/Receptor Interacting Serine Threonine Kinase 3/Mixed Lineage Kinase Domain-Like and Mitogen-Activated Protein Kinase Signaling

“…In summary, our data revealed the differential regulation of dietary Se deficiency on 25 selenoprotein genes, 7 key selenoproteins, and the RIPK1/RIPK3/MLKL and MAPK signaling pathway proteins in chicks and provided new molecular clues for understanding the pathogenesis of liver necrosis. The protective effects of Se are probably exerted via peroxide scavenging, controlling oxidative stress, and regulating subsequent stress signaling (Miyata et al, 2020). As shown in Figure 5, the main stress signaling proteins were activated, including p38 MAPK, JNK, and ERK.…”