Nicotinamide riboside ameliorates high-fructose-induced lipid metabolism disorder in mice via improving FGF21 resistance in the liver and white adipose tissue.

Fructose has been reported to acutely elevate the circulating fibroblast growth factor 21 (FGF21) levels, which ultimately causes FGF21 resistance. FGF21 resistance is suggested to result in lipid metabolism disorder. Nicotinamide riboside (NR) can alleviate lipid metabolism disorder in mice. It is unknown whether NR supplementation would alleviate lipid metabolism disorder in high-fructose exposed mice via improving FGF21 resistance. In this study, C57BL/6J mice were given 20% fructose solution for free drinking with the supplementation of NR in 400 mg kg-1 day-1. The results showed that NR supplementation decreased the serum and hepatic lipid profile levels. The increase of lipid droplets in the liver and the size of adipose cells in WAT induced by a high-fructose diet were alleviated by the addition of NR. NR supplementation increased the NAD+/NADH ratio and activated the SIRT1/NF-κB pathway. The down-regulation of NF-κB is accompanied by a decrease in inflammation, which may increase the expression of the FGF21 receptor complex, namely KLB and FGFR, then restore its downstream signaling cascade, including ERK phosphorylation and EGR1 and c-FOS expression, and ultimately improve FGF21 resistance. With the FGF21 function recovery, hepatic PGC-1α expression was up-regulated, and hepatic SREBP-1c expression was down-regulated, resulting in decreased lipogenesis. Furthermore, restoration of the FGF21 signaling pathway also led to increased expression of ATGL and HSL in WAT, which promotes lipolysis. In conclusion, we found that NR supplementation could ameliorate high-fructose-induced lipid metabolism disorder by improving FGF21 resistance in the liver and WAT, which may be related to the regulation of inflammation mediated by the SIRT1/NF-κB signaling pathway.

Protective effect of fucoidan against iron overload and ferroptosis-induced liver injury in rats exposed to alcohol.

This study was aimed to explore the effects of fucoidan on iron overload and ferroptosis-induced liver injury, and the underlying mechanisms in rats exposed to alcohol. Sprague-Dawley rats were used to establish alcoholic liver injury model by intragastric administration with alcohol for 16 weeks. The results showed that fucoidan treatment reversed alcohol-induced increases in reactive oxygen species and malondialdehyde levels, and increased glutathione peroxidase and glutathione levels, thus protecting against liver damage. Long-term alcohol feeding resulted in abnormal increase of serum ferritin, liver total iron and the "free" iron levels. Fucoidan treatment reduced serum ferritin level and alleviated liver iron deposition. Fucoidan reversed the reduction of hepcidin induced by alcohol exposure and decreased divalent metal transporter 1 (DMT1) and ferroportin1 (FPN1) expressions in the duodenum. Electron microscope observation of liver tissues showed that alcohol exposure induced ferroptosis changes in the liver. However, fucoidan treatment could alleviate alcohol-induced ferroptosis via upregulating the expressions of p62, Nrf2, SLC7A11 and GPX4. The liver endogenous metabolites analysis by liquid chromatography and mass spectrometry showed that after fucoidan intervention, mineral absorption, biosynthesis of amino acids pathways and lipid metabolism were changed. Fucoidan intervention reduced the levels of oxidized glutathione and regulated the levels of phosphatidylethanolamines in liver tissues. Our data showed that fucoidan supplementation could inhibit iron load via regulating hepcidin-intestinal DMT1/FPN1 axis, alleviate the liver oxidative damage and protect hepatocytes from ferroptosis induced by long-term alcohol exposure through upregulating p62/Nrf2/SLC7A11 pathway in rats.

Resveratrol preserves mitochondrial function, stimulates mitochondrial biogenesis, and attenuates oxidative stress in regulatory T cells of mice fed a high-fat diet.

Consumption of high-fat diet (HFD) is related with increased oxidative stress and dysfunctional mitochondria in many organs. The effects of resveratrol (trans-3,5,4'-trihydroxystilbene) that can protect T lymphocytes in various disease conditions on the HFD-induced apoptosis of CD4(+) CD25(+) CD127(low/-) regulatory T cells (Tregs) were studied, and the possible mechanism was postulated. Resveratrol significantly decreased Tregs death induced by 20-wk HFD, being associated with the reduction of reactive oxygen species production and the alleviation of HFD-induced loss of mitochondrial membrane potential (Δψm) in Tregs. Furthermore, resveratrol increased the expression of factors that regulated mitochondrial biogenesis in Tregs. Finally, resveratrol recovered the HFD-induced activation of apoptotic markers in Tregs. Resveratrol protected Tregs against HFD-induced apoptosis by reducing oxidative stress, restoring mitochondrial functional activities, and stimulating mitochondrial biogenesis.