Regulation of Polyunsaturated Fatty Acid Biosynthesis by Seaweed Fucoxanthin and Its Metabolite in Cultured Hepatocytes

Abstract

The effects of a seaweed carotenoid, fucoxanthin, and its physiological metabolite, fucoxanthinol, on the biosynthesis of polyunsaturated fatty acids (PUFA) were investigated using cultured rat hepatoma BRL-3A. The metabolism of α-linolenic acid (18:3n-3) was suppressed by the addition of these carotenoids, resulting in a decrease in the content of eicosapentaenoic acid (20:5n-3), which suggested a down-regulation of metabolic enzymes such as fatty acid desaturase and elongase. An increase in the content of docosahexaenoic acid (22:6n-3), as observed in previous studies in vivo, might be a buffering action to maintain the membrane fluidity. The suppressive effect of fucoxanthinol on ∆6 fatty acid desaturase was not at the level of gene expression but due to specific modifications of the protein via a ubiquitin-proteasome system. A proteomic analysis revealed several factors such as phosphatidylethanolamine-binding protein that might be involved in the observed action of fucoxanthin. These findings will contribute to studies on the elucidation of the precise molecular mechanisms underlying the regulation of PUFA biosynthesis by fucoxanthin.

Fucoxanthin Enhances Chain Elongation and Desaturation of Alpha‐Linolenic Acid in HepG2 Cells

“…As HepG2 cells were more commonly used in the studies of longer chains PUFA conversions [17,18], we traced universally-[ 13 C]-labeled (U-[ 13 C]-) ALA metabolism in this cell line to examine the effect of FX. At ALA and FX concentrations that are higher than those previously reported [16], our results agree with those obtained from rodent studies [12][13][14][15] that FX enhanced conversion of ALA to EPA and DHA. This may be related to increased D5D, but not D6D activities.…”

“…Our data of the present study supported these finding that fucoxanthin increased EPA, DPA and DHA in HepG2 cells treated with ALA. We further demonstrated enhanced conversion of ALA to EPA, DPA and DHA in cells co-treated with FX by isotope tracking. A previous study by Aki et al aimed to delineate the mechanism using cultured rat hepatoma BRL-3A cells, however, they found decreases in EPA and no changes in DHA [16]. Compared to our study, Aki et al used lower concentrations of not only ALA (50 μM) but also FX (10 μM).…”

“…Based on our results of Exp 1, higher concentrations of FX are required to observe significant differences in levels of EPA, DPA and DHA (Table 1). Moreover, they incubated cells for 8 and 24 h [16]. Our results of Exp 2 indicate that enhancing effects of FX on the conversion of ALA to EPA, DPA and DHA were observed at 48 h of incubation and not at 24 h. More studies using other cell lines or liver microsomes would be of interest.…”

“…A few studies observed that dietary FX enriches hepatic EPA, DHA and arachidonic acid (ARA) content in rodents [12][13][14][15]. In contrast, a study using rat hepatoma BRL-3A cells observed a suppression of EPA from ALA by fucoxanthin and fucoxanthinol [16]. As HepG2 cells were more commonly used in the studies of longer chains PUFA conversions [17,18], we traced universally-[ 13 C]-labeled (U-[ 13 C]-) ALA metabolism in this cell line to examine the effect of FX.…”

Inhibitory effects of high stability fucoxanthin on palmitic acid-induced lipid accumulation in human adipose-derived stem cells through modulation of long non-coding RNA

“…Since 2006, the inhibitory effects of fucoxanthin and fucoxanthinol against adipogenesis have been demonstrated. 22,23 In a noted human study, after 1 week of uptake of fucoxanthin, the results showed that except fucoxanthinol, neither fucoxanthin nor amarouciaxanthin A was detected in the plasma; the possible argument was that some components (e.g., dietary fibre) in algal matrix inhibited the intestinal absorption of fucoxanthin. 24 The bioavailability of fucoxanthinol is higher than the fucoxanthin in the body.…”