Molecular Mechanisms of Fucoxanthin in Alleviating Lipid Deposition in Metabolic Associated Fatty Liver Disease

Abstract

Metabolic-associated fatty liver disease (MAFLD) is witnessing a global surge; however, it still lacks effective pharmacological interventions. Fucoxanthin, a natural bioactive metabolite derived from marine brown algae, exhibits promising pharmacological functions, particularly in ameliorating metabolic disorders. However, the mechanisms underlying its therapeutic efficacy in addressing MAFLD remain elusive. Our present findings indicated that fucoxanthin significantly alleviated palmitic acid (PA)-induced hepatic lipid deposition in vitro and obesity-induced hepatic steatosis in ob/ob mice. Moreover, at both the protein and transcriptional levels, fucoxanthin effectively increased the expression of PPARα and CPT1 (involved in fatty acid oxidation) and suppressed FASN and SREBP1c (associated with lipogenesis) in both PA-induced HepG2 cells and hepatic tissues in ob/ob mice. This modulation was accompanied by the activation of AMPK. The capacity of fucoxanthin to improve hepatic lipid deposition was significantly attenuated when utilizing the AMPK inhibitor or siRNA-mediated AMPK silencing. Mechanistically, fucoxanthin activates AMPK, subsequently regulating the KEAP1/Nrf2/ARE signaling pathway to exert antioxidative effects and stimulating the PGC1α/NRF1 axis to enhance mitochondrial biogenesis. These collective actions contribute to fucoxanthin's amelioration of hepatic steatosis induced by metabolic perturbations. These findings offer valuable insights into the prospective utilization of fucoxanthin as a therapeutic strategy for managing MAFLD.

Effects of Marine Natural Products on Liver Diseases

“…These combined effects contribute to the amelioration of hepatic steatosis caused by metabolic disorders by Fx. These findings provide valuable insights into the use of Fx as a therapeutic strategy for the treatment of ALD [48], and it is interesting to note that Fx can also play an important role in NAFLD; therefore, Fx is considered a valuable natural product for treating liver disease [49].…”

Fucoxanthin Mitigates High-Fat-Induced Lipid Deposition and Insulin Resistance in Skeletal Muscle through Inhibiting PKM1 Activity

“…A 100 mM stock solution of PA was prepared according to previous literature by repeatedly incubating it in a 70 °C water bath and vigorously vortexing . The PA solution was then filtered and stored at 4 °C until use.…”