Nuclear factor interleukin 3 and metabolic dysfunction-associated fatty liver disease development.

This study investigates sex-specific effects in a gain-of-function model to evaluate Nfil3 function in relation to high-fat diet (HFD)-induced metabolic dysfunction-associated steatotic liver disease (MASLD) and gut microbiota (GM)-induced alterations in the bile acid (BA) profile. MASLD is induced in both wild type and Nfil3-deficient (NKO) C57BL/6 J mice through an HFD. The hepatic immune response is evaluated using flow cytometry, revealing that NKO mice exhibit lower body weight, serum triglyceride (TG) levels, tissue injury, inflammation, and fat accumulation. The Nfil3 deletion reduces macrophage counts in fibrotic liver tissues, decreases proinflammatory gene and protein expression, and diminishes gut barrier function. Alpha and beta diversity analysis reveal increased GM alpha diversity across different sexes. The Nfil3 gene deletion modifies the BA profile, suggesting that negative feedback through the Nfil3-FXR-FGF15 axis facilitates BA recycling from the liver via enterohepatic circulation. Therefore, inhibiting Nfil3 in the liver offers a viable treatment approach for MASLD.

Sulforaphane inhibits blue light-induced inflammation and apoptosis by upregulating the SIRT1/PGC-1α/Nrf2 pathway and autophagy in retinal pigment epithelial cells.

The present study elucidated mechanisms through which sulforaphane (SFN) protects retinal pigment epithelial (RPE) cells from blue light-induced impairment. SFN could activate the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and increase the expression of the heme oxygenease-1 (HO-1) gene and production of glutathione. SFN reduced blue light-induced oxidative stress, and effectively activated cytoprotective components including Nrf-2, HO-1, thioredoxin-1, and glutathione. The protective effect of SFN on blue light-induced injury was blocked by the Nrf2 inhibitor ML385, suggesting that the SFN-induced Nrf2 pathway is involved in the cytoprotective effect of SFN. SFN inhibited intercellular adhesion molecule-1 expression induced by TNF-α or blue light, suggesting the anti-inflammatory activity of SFN. The inhibitory effect of SFN was associated with the blocking of NF-κB p65 nuclear translocation in blue light-exposed RPE cells. SFN protected RPE cells from blue light-induced interruption of the mitochondrial membrane potential and reduction of the Bcl-2/Bax ratio and cleaved caspase-3 and PARP-1 expression, suggesting the antiapoptotic activity of SFN. SFN alone or together with blue light exposure increased the expression of the autophagy-related proteins LC3BII and p62. An autophagy inhibitor, 3-MA, inhibited the protective effect of SFN on blue light-induced cell damage. SFN increased sirtuin-1 (SIRT1) expression; however, treatment with blue light induced peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) expression. Our study results demonstrated that SFN exerts its protective effect under blue light exposure by maintaining the Nrf2-related redox state and upregulating SIRT1 and PGC-1α expression and autophagy.