Chronic liver disease (CLD) has emerged as a leading cause of human deaths. It caused 1.32 million deaths in 2017, which affected men more than women by a two-to-one ratio. There are various causes of CLD, including obesity, excessive alcohol consumption, and viral infection. Among them, non-alcoholic fatty liver disease (NAFLD), one of obesity-induced liver diseases, is the major cause, representing the cause of more than 50% of cases. Fucoxanthin, a carotenoid mainly found in brown seaweed, exhibits various biological activities against NAFLD. Its role in NAFLD appears in several mechanisms, such as inducing thermogenesis in mitochondrial homeostasis, altering lipid metabolism, and promoting anti-inflammatory and anti-oxidant activities. The corresponding altered signaling pathways are the β3-adorenarine receptor (β3Ad), proliferator-activated receptor gamma coactivator (PGC-1), adenosine monophosphate-activated protein kinase (AMPK), peroxisome proliferator-activated receptor (PPAR), sterol regulatory element binding protein (SREBP), nuclear factor kappa B (NF-κB), mitogen-activated protein kinase (MAPK), protein kinase B (AKT), SMAD2/3, and P13K/Akt pathways. Fucoxanthin also exhibits anti-fibrogenic activity that prevents non-alcoholic steatohepatitis (NASH) development.

This study aimed to investigate the regulation of fucoxanthin (FX) biosynthesis under various nitrogen conditions to optimize FX productivity in Phaeodactylum tricornutum. Apart from light, nitrogen availability significantly affects the FX production of microalgae; however, the underlying mechanism remains unclear. In batch culture, P. tricornutum was cultivated with normal (NN, 0.882 mM sodium nitrate), limited (LN, 0.22 mM), and high (HN, 8.82 mM) initial nitrogen concentrations in f/2 medium. Microalgal growth and photosynthetic pigment production were examined, and day 5 samples were subjected to fucoxanthin–chlorophyll a/c-binding protein (FCP) proteomic and transcriptomic analyses. The result demonstrated that HN promoted FX productivity by extending the exponential growth phase for higher biomass and FX accumulation stage (P1), showing a continuous increase in FX accumulation on day 6. Augmented FX biosynthesis via the upregulation of carotenogenesis could be primarily attributed to enhanced FCP formation in the thylakoid membrane. Key proteins, such as LHC3/4, LHCF8, LHCF5, and LHCF10, and key genes, such as PtPSY, PtPDS, and PtVDE, were upregulated under nitrogen repletion. Finally, the combination of low light and HN prolonged the P1 stage to day 10, resulting in maximal FX productivity to 9.82 ± 0.56 mg/L/day, demonstrating an effective strategy for enhancing FX production in microalgae cultivation.