Gut microbiota mediates the effects of diet, thereby modifying host metabolism and the incidence of metabolic disorders. Increased consumption of omega-6 polyunsaturated fatty acid (PUFA) that is abundant in Western diet contributes to obesity and related diseases. Although gut-microbiota-related metabolic pathways of dietary PUFAs were recently elucidated, the effects on host physiological function remain unclear. Here, we demonstrate that gut microbiota confers host resistance to high-fat diet (HFD)-induced obesity by modulating dietary PUFAs metabolism. Supplementation of 10-hydroxy-cis-12-octadecenoic acid (HYA), an initial linoleic acid-related gut-microbial metabolite, attenuates HFD-induced obesity in mice without eliciting arachidonic acid-mediated adipose inflammation and by improving metabolic condition via free fatty acid receptors. Moreover, Lactobacillus-colonized mice show similar effects with elevated HYA levels. Our findings illustrate the interplay between gut microbiota and host energy metabolism via the metabolites of dietary omega-6-FAs thereby shedding light on the prevention and treatment of metabolic disorders by targeting gut microbial metabolites.

We investigated whether various carotenoids present in foodstuffs were potentially involved in cancer-preventing action on human prostate cancer. The effects of 15 kinds of carotenoids on the viability of three lines of human prostate cancer cells, PC-3, DU 145 and LNCaP, were evaluated. When the prostate cancer cells were cultured in a carotenoid-supplemented medium for 72 h at 20 μmol/L, 5,6-monoepoxy carotenoids, namely, neoxanthin from spinach and fucoxanthin from brown algae, significantly reduced cell viability to 10.9 and 14.9% for PC-3, 15.0 and 5.0% for DU 145, and nearly zero and 9.8% for LNCaP, respectively. Acyclic carotenoids such as phytofluene, ζ-carotene and lycopene, all of which are present in tomato, also significantly reduced cell viability. On the other hand, phytoene, canthaxanthin, β-cryptoxanthin and zeaxanthin did not affect the growth of the prostate cancer cells. DNA fragmentation of nuclei in neoxanthin- and fucoxanthin-treated cells was detected by in situ TdT-mediated dUTP nick end labeling (TUNEL) assay. Neoxanthin and fucoxanthin were found to reduce cell viability through apoptosis induction in the human prostate cancer cells. These results suggest that ingestion of leafy green vegetables and edible brown algae rich in neoxanthin and fucoxanthin might have the potential to reduce the risk of prostate cancer.

Despite the interest in the beneficial roles of dietary carotenoids in human health, little is known about their solubilization from foods to mixed bile micelles during digestion and the intestinal uptake from the micelles. We investigated the absorption of carotenoids solubilized in mixed micelles by differentiated Caco-2 human intestinal cells, which is a useful model for studying the absorption of dietary compounds by intestinal cells. The micelles were composed of 1 μmol/L carotenoids, 2 mmol/L sodium taurocholate, 100 μmol/L monoacylglycerol, 33.3 μmol/L fatty acid and phospholipid (0–200 μmol/L). The phospholipid content of micelles had profound effects on the cellular uptake of carotenoids. Uptake of micellar β-carotene and lutein was greatly suppressed by phosphatidylcholine (PC) in a dose-dependent manner, whereas lysophosphatidylcholine (lysoPC), the lipolysis product of PC by phospholipase A₂ (PLA₂), markedly enhanced both β-carotene and lutein uptake. The addition of PLA₂ from porcine pancreas to the medium also enhanced the uptake of carotenoids from micelles containing PC. Caco-2 cells could take up 15 dietary carotenoids, including epoxy carotenoids, such as violaxanthin, neoxanthin and fucoxanthin, from micellar carotenoids, and the uptakes showed a linear correlation with their lipophilicity, defined as the distribution coefficient in 1-octanol/water (log P_ow). These results suggest that pancreatic PLA₂ and lysoPC are important in regulating the absorption of carotenoids in the digestive tract and support a simple diffusion mechanism for carotenoid absorption by the intestinal epithelium.

Fucoxanthin, a major carotenoid in edible brown algae, potentially inhibits the proliferation of human prostate cancer cells via apoptosis induction. However, it has been postulated that dietary fucoxanthin is hydrolyzed into fucoxanthinol in the gastrointestinal tract before absorption in the intestine. In the present study, we investigated the further biotransformation of orally administered fucoxanthin and estimated the cytotoxicity of fucoxanthin metabolites on PC-3 human prostate cancer cells. After the oral administration of fucoxanthin in mice, two metabolites, fucoxanthinol and an unknown metabolite, were found in the plasma and liver. The unknown metabolite was isolated from the incubation mixture of fucoxanthinol and mouse liver preparation (10,000gsupernatant of homogenates), and a series of instrumental analyses identified it as amarouciaxanthin A [(3S,5R,6′S)-3,5,6′-trihydroxy-6,7-didehydro-5,6,7′,8′-tetrahydro-β,ϵ-carotene-3′,8′-dione]. The conversion of fucoxanthinol into amarouciaxanthin A was predominantly shown in liver microsomes. This dehydrogenation/isomerization of the 5,6-epoxy-3-hydroxy-5,6-dihydro-βend group of fucoxanthinol into the 6′-hydroxy-3′-oxo-ϵend group of amarouciaxanthin A required NAD(P)⁺ as a cofactor, and the optimal pH for the conversion was 9.5 to 10.0. Fucoxanthinol supplemented to culture medium via HepG2 cells was also converted into amarouciaxanthin A. The 50% inhibitory concentrations on the proliferation of PC-3 human prostate cancer cells were 3.0, 2.0, and 4.6 μM for fucoxanthin, fucoxanthinol, and amarouciaxanthin A, respectively. To our knowledge, this is the first report on the enzymatic dehydrogenation of a 3-hydroxyl end group of xanthophylls in mammals.

The metabolic fate in mammals of dietary fucoxanthin, a major carotenoid in brown algae, is not known. We investigated the absorption and metabolism of fucoxanthin in differentiated Caco-2 human intestinal cells, a useful model for studying the absorption of dietary compounds by intestinal cells. Fucoxanthin was taken up by Caco-2 cells incubated with micellar fucoxanthin composed of 1 μmol/L fucoxanthin, 2 mmol/L sodium taurocholate, 100 μmol/L monoacylglycerol, 33.3 μmol/L fatty acids and 50 μmol/L lysophosphatidylcholine. Fucoxanthinol, the deacetylated product of fucoxanthin, was also found in both medium and cells, with its level increasing significantly in a time-dependent manner. No conjugated forms of fucoxanthin and fucoxanthinol were found in either medium or cells. In the animal study, fucoxanthinol (10.4 ± 5.3 nmol/L plasma, n = 4) was detected in plasma of mice 1 h after intubation of 40 nmol fucoxanthin. These results indicate that dietary fucoxanthin is incorporated as fucoxanthinol, the deacetylated form, from the digestive tract into the blood circulation system in mammals.