No abstract

Obesity and type 2 diabetes are pathologies with rapidly growing prevalence throughout the world. A few molecular targets offer the most hope for anti-obesity and anti-diabetic therapeutics. One of the keys to success will be the induction of uncoupling protein 1 (UCP1) in abdominal white adipose tissue (WAT) and the regulation of cytokine secretions from both abdominal adipose cells and macrophage cells infiltrated into adipose tissue. Anti-obesity and anti-diabetic effects of fucoxanthin, a characteristic carotenoid found in brown seaweeds, have been reported. Nutrigenomic studies reveal that fucoxanthin induces UCP1 in abdominal WAT mitochondria, leading to the oxidation of fatty acids and heat production in WAT. Fucoxanthin improves insulin resistance and decreases blood glucose levels through the regulation of cytokine secretions from WAT. The key structure of carotenoids for the expression of anti-obesity effect is suggested to be the carotenoid end of the polyene chromophore, which contains an allenic bond and two hydroxyl groups.

-Fucoxanthin (FX), a xanthophyll derivative, is an orange-colored pigment present in edible brown algae. As a part of safety evaluation, single and repeated oral dose toxicity study of FX was ICR mice at doses of 1,000 and 2,000 mg/kg. In a repeated doses study, FX at doses of 500 and 1,000 appearance were observed. In the repeated doses study, histological observation revealed no abnormal -ly increased total cholesterol concentrations were shown by plasma biochemical analyses in all FX-treated groups. Although total bilirubin concentrations were increased by FX, it was established that presence of fucoxanthinol, a major metabolite of FX, interfered with bilirubin determination in plasma. To further ascertain the safety of FX, the mechanism by which FX induces hypercholesterolemia in mice and species differences in the induction of hypercholesterolemia should be elucidated.

This study compared the growth inhibitory effects of pure conjugated linoleic acid (CLA) isomers (cis(c)9,c11-CLA, c9,trans(t)11-CLA, t9,t11-CLA, and t10,c12-CLA) on human colon cancer cell lines (Caco-2, HT-29, and DLD-1). When Caco-2 cells were incubated up to 72 h with 200 M each isomer even in the presence of 10% fetal bovine serum (FBS), cell proliferation was inhibited by all CLA isomers in a time dependent manner. The strongest inhibitory effect was shown by t9,t11-CLA, followed by t10,c12-CLA, c9,c11-CLA, and c9,t11-CLA, respectively. The strongest effect of t9,t11-CLA was also observed in other colon cancer cell lines (HT-29 and DLD-1). The order of the inhibitory effect of CLA isomer was confirmed in the presence of 1% FBS. CLA isomers supplemented in the culture medium were readily incorporated into the cellular lipids of Caco-2 and changed their fatty acid composition. The CLA contents in cellular lipids were 26.2+2.7% for t9,t11-CLA, 35.9+0.3% for c9,t11-CLA, and 46.3+0.8% for t10,c12-CLA, respectively. DNA fragmentation was clearly recognized in Caco-2 cells treated with t9,t11-CLA. This apoptotic effect of t9,t11-CLA was dose-and time-dependent. DNA fragmentation was also induced by 9c,11t-CLA and t10,c12-CLA. However, fragmentation levels with both isomers were much lower than that with t9,t11-CLA.t9t11-CLA treatment of Caco-2 cells decreased Bcl-2 levels in association with apoptosis, whereas Bax levels remained unchanged. These results suggest that decreased expression of Bcl-2 by t9t11-CLA might increase the sensitivity of cells to lipid peroxidation and to programmed cell death, apoptosis. AbstractThis study compared the growth inhibitory effects of pure conjugated linoleic acid (CLA) isomers (cis(c)9,c11-CLA, c9,trans(t)11-CLA, t9,t11-CLA, and t10,c12-CLA) on human colon cancer cell lines (Caco-2, HT-29, and DLD-1). When Caco-2 cells were incubated up to 72 h with 200 µM each isomer even in the presence of 10% fetal bovine serum (FBS), cell proliferation was inhibited by all CLA isomers in a time dependent manner. The strongest inhibitory effect was shown by t9,t11-CLA, followed by t10,c12-CLA, c9,c11-CLA, and c9,t11-CLA, respectively. The strongest effect of t9,t11-CLA was also observed in other colon cancer cell lines (HT-29 and DLD-1). The order of the inhibitory effect of CLA isomer was confirmed in the presence of 1% FBS. * Manuscript 2CLA isomers supplemented in the culture medium were readily incorporated into the cellular lipids of Caco-2 and changed their fatty acid composition. The CLA contents in cellular lipids were 26.2+2.7% for t9,t11-CLA, 35.9+0.3% for c9,t11-CLA, and 46.3+0.8% for t10,c12-CLA, respectively. DNA fragmentation was clearly recognized in Caco-2 cells treated with t9,t11-CLA. This apoptotic effect of t9,t11-CLA was doseand time-dependent. DNA fragmentation was also induced by 9c,11t-CLA and t10,c12-CLA. However, fragmentation levels with both isomers were much lower than that with t9,t11-CLA. t9t11-CLA treatment of Caco-2 cells decreased Bcl-2 levels in...

Fucoxanthin (Fx), a major carotenoid found in brown seaweed, is known to show a unique and wide variety of biological activities. Upon absorption, Fx is metabolized to fucoxanthinol and amarouciaxanthin, and these metabolites mainly accumulate in visceral white adipose tissue (WAT). As seen in other carotenoids, Fx can quench singlet oxygen and scavenge a wide range of free radicals. The antioxidant activity is related to the neuroprotective, photoprotective, and hepatoprotective effects of Fx. Fx is also reported to show anti-cancer activity through the regulation of several biomolecules and signaling pathways that are involved in either cell cycle arrest, apoptosis, or metastasis suppression. Among the biological activities of Fx, anti-obesity is the most well-studied and most promising effect. This effect is primarily based on the upregulation of thermogenesis by uncoupling protein 1 expression and the increase in the metabolic rate induced by mitochondrial activation. In addition, Fx shows anti-diabetic effects by improving insulin resistance and promoting glucose utilization in skeletal muscle.