Fucoxanthin Attenuates Free Fatty Acid-Induced Nonalcoholic Fatty Liver Disease by Regulating Lipid Metabolism/Oxidative Stress/Inflammation via the AMPK/Nrf2/TLR4 Signaling Pathway

Abstract

Fucoxanthin, a xanthophyll carotenoid abundant in brown algae, is reported to have several biological functions, such as antioxidant, anti-inflammatory, and anti-tumor activities, in mice. We investigated the effects and mechanisms of fucoxanthin in the mixture oleate/palmitate = 2/1(FFA)-induced nonalcoholic fatty liver disease (NAFLD) cell model in this study. The results showed that the content of superoxide dismutase in the FFA group was 9.8 ± 1.0 U/mgprot, while that in the fucoxanthin high-dose (H-Fx) group (2 μg/mL) increased to 22.9 ± 0.6 U/mgprot. The content of interleukin-1β in the FFA group was 89.3 ± 3.6 ng/mL, while that in the H-Fx group was reduced to 53.8 ± 2.8 ng/mL. The above results indicate that fucoxanthin could alleviate the FFA-induced oxidative stress and inflammatory levels in the liver cells. Oil red-O staining revealed visible protrusions and a significant decrease in the number of lipid droplets in the cytoplasm of cells in the fucoxanthin group. These findings on the mechanisms of action suggest that fucoxanthin can repair FFA-induced NAFLD via the adenosine monophosphate-activated protein kinase (AMPK) signaling pathway and nuclear factor erythroid-2-related factor 2-mediated (Nrf2) signaling pathway, as well as by downregulating the expression of the Toll-like receptor 4-mediated (TLR4) signaling pathway. Fucoxanthin exhibited alleviating effects in the FFA-induced NAFLD model and could be explored as a potential anti-NAFLD substance.

Plantamajoside modulates immune dysregulation and hepatic lipid metabolism in rats with nonalcoholic fatty liver disease viaAMPK/Nrf2 elevation

“…AMPK widely distributes in the liver and skeletal muscle that modulates the lipid metabolism. The phosphorylated level of AMPK is the major kinase modulator of the downstream lipogenic enzymes, such as SREBP1, acetyl‐CoA carboxylase, and fatty acid synthase, which are tightly involved in the fatty acid synthesis 36 . Nrf2 plays an important role in neutralizing oxidative stress and conserving redox homeostasis in the cell through the generation of cytoprotective and antioxidant enzymes, such as HO‐1 and NQO1 37 .…”

Bioactive Compounds from Brown Algae Alleviate Nonalcoholic Fatty Liver Disease: An Extensive Review

“…Fucoxanthin restored FFA-induced NAFLD by downregulating the toll-like receptor 4 (TLR4)-mediated signaling pathway and the AMPK and Nrf2 signaling pathways. 126 4.4. Other Compounds.…”

“…LMF-HSFx has a role in reversing liver fibrosis in NAFLD patients, thus its effects and their correlations with IL-6 in Kupffer cells should be elucidated to reveal the underlying mechanism. Fucoxanthin restored FFA-induced NAFLD by downregulating the toll-like receptor 4 (TLR4)-mediated signaling pathway and the AMPK and Nrf2 signaling pathways …”

DHA-enriched phosphatidylcholine from Clupea harengus roes regulates the gut–liver axis to ameliorate high-fat diet-induced non-alcoholic fatty liver disease

“…The epididymal fat, liver, and jejunum tissues were embedded in paraffin, and H&E and Oil Red O staining procedures were done as previously described. [30][31][32] The immunohistochemical analysis was performed with primary antibodies of ZO-1, occludin, and claudin-4, and stained with diaminobenzidine-tetrahydrochloride (DAB). The sections were observed under an optical microscope.…”