The Green Algal Carotenoid Siphonaxanthin Inhibits Adipogenesis in 3T3-L1 Preadipocytes and the Accumulation of Lipids in White Adipose Tissue of KK-Ay Mice

Li, Zhuosi; Noda, Kenji; Fujita, Eriko; Manabe, Yuki; Hirata, Takashi; Sugawara, Tatsuya

doi:10.3945/jn.114.200931

Cited by 45 publications

(39 citation statements)

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“…Although these green algae have been eaten for a long time, especially in Japan, studies on intestinal absorption of siphonaxanthin are limited. In a recent study, we showed that when mice were subjected to a daily intake of siphonaxanthin (1.3 mg/mouse dissolved in 100 μL triolein) over a period of 6 weeks, it resulted in its accumulation in mesenteric white adipose tissues (389.8 ± 30.2 ng/g tissue) (Li et al, ). In addition, we found that, in green algal powder‐fed mice, whose daily siphonaxanthin intake was around 31.1 μg over a period of 78 days, the carotenoid accumulated in mesenteric white adipose tissues (5.57 ± 1.80 ng/g tissue) (Li et al, ).…”

Section: Introductionmentioning

confidence: 99%

“…These results indicated that siphonaxanthin was absorbed from the diet. Moreover, we reported various activities of siphonaxanthin that could be potential health benefits, such as apoptosis‐inducing effect on cancer cells (Ganesan et al, ), anti‐obesity effect (Li et al, ), inhibitory effect on hepatocyte lipogenesis (Zheng et al, ), and anti‐inflammatory effect (Manabe et al, , , b). To explore these biological activities, information on the intestinal absorption mechanism of siphonaxanthin is mandatory.…”

Section: Introductionmentioning

confidence: 99%

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Niemann‐Pick C1‐like 1 Promotes Intestinal Absorption of Siphonaxanthin

Manabe

Ichihara

Fukuda

et al. 2019

Lipids

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Siphonaxanthin is a carotenoid found in certain green algae, and its promising beneficial properties, such as its anti‐obesity effect, have recently been demonstrated. However, there is little information about the molecular mechanisms underlying intestinal absorption of siphonaxanthin. In this study, we aimed to elucidate how siphonaxanthin is transported across the intestinal epithelium using differentiated Caco‐2 cells (dCaco‐2 cells), recombinant proteins, and an animal model. Siphonaxanthin was taken up by dCaco‐2 cells, a model of intestinal epithelial cells, and its uptake linearly increased up to at least 6 h. Pharmacological inhibition of Nieman‐Pick C1‐like 1 (NPC1L1), but not that of scavenger receptor class B type 1 (SR‐B1), significantly suppressed siphonaxanthin uptake by dCaco‐2 cells. Results from an in vitro binding assay suggested that the N‐terminal domain of NPC1L1, which is an extracellular domain of NPC1L1, binds with siphonaxanthin. Moreover, pretreatment with ezetimibe, an inhibitor of NPC1L1, significantly decreased the plasma level of siphonaxanthin following oral administration in mice. Considered together, we concluded that NPC1L1 promotes siphonaxanthin transport across the intestinal epithelium.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Niemann‐Pick C1‐like 1 Promotes Intestinal Absorption of Siphonaxanthin

Manabe

Ichihara

Fukuda

et al. 2019

Lipids

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“…Following this study, it is plausible to speculate that SPX may have some unique effect targeting pathological liver disorders such as NAFLD/NASH. Previously, we have reported that SPX inhibited mast cell degranulation and showed anti obesity activity in a diabetic and obese rodent model (Li et al, ; Manabe et al, ). These reports, in other aspects, together with this research indicate that SPX may be biologically multifunctional through exhibiting anti‐inflammation, anti obesity, and hepatoprotective effects.…”

Section: Discussionmentioning

confidence: 92%

“…) is a rare marine carotenoid abundant in green algae such as Codium fragile , Umbraulva japonica , and Caulerpa lentillifera (Sugawara, Ganesan, Li, Manabe, & Hirata, ). To date, antiangiogenesis, anti degranulation, and anti obesity effects of SPX have been reported but its effect on hepatic lipid metabolism remains unexplored (Ganesan et al, ; Li et al, ; Manabe, Hirata, & Sugawara, ). Siphonein (SPN; Fig.…”

Section: Introductionmentioning

confidence: 99%

Siphonaxanthin, a Carotenoid From Green Algae, Inhibits Lipogenesis in Hepatocytes via the Suppression of Liver X Receptor α Activity

Zheng

Manabe

et al. 2018

Lipids

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Nonalcoholic fatty liver disease (NAFLD) has shown an increasing morbidity in recent years. Here, we demonstrated that siphonaxanthin (SPX), a rare marine carotenoid, exhibits a strong inhibitory effect on aggravated hepatic lipogenesis in vitro and would be a promising candidate in the prevention and alleviation of NAFLD in the future. In this study, we conducted a preliminary assessment of the effect of SPX on hepatic lipogenesis by using the HepG2 cell line, derived from human liver cancer, as a model of the liver. SPX significantly suppressed the excess accumulation of triacylglycerol induced by liver X receptor α (LXRα) agonist by downregulating a nuclear transcription factor named sterol regulatory element-binding protein-1c and a set of related genes. Moreover, fatty acid translocase (CD36) and fatty acid-binding protein-1, which regulates fatty acid uptake, also exhibited significant decrease in transcriptional levels. Furthermore, we found that SPX blocked LXRα activation and would be a promising candidate for antagonist of LXRα.

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“…Siphonaxanthin administration reduced the total weight of WAT, especially the mesenteric WAT in KK-Ay mice, and enhanced fatty acid oxidation in adipose tissue. 116 Okada et al 117 tested the suppressive effects of 13 naturally occurring carotenoids (lutein, violaxanthin, α-carotene, β-carotene 5,6-epoxide, canthaxanthin, citranaxanthin, rhodoxanthin, β-cryptoxanthin, antheraxanthin, lutein epoxide, neoxanthin, and capsorubin) on 3T3L1 adipocyte differentiation. They demonstrated that neoxanthin reduced intracellular lipid accumulation and the expression of C/ EBPα and PPARγ mRNAs without affecting the expression of C/EBPβ or C/EBPγ mRNAs.…”

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Role of PPARγ in the nutritional and pharmacological actions of carotenoids

Wang¹,

Shi²,

Gu³

et al. 2016

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Peroxisome proliferator-activated receptor gamma (PPARγ) has been shown to play an important role in the biological effects of carotenoids. The PPARγ-signaling pathway is involved in the anticancer effects of carotenoids. Activation of PPARγ partly contributes to the growth-inhibitory effects of carotenoids (β-carotene, astaxanthin, bixin, capsanthin, lutein, and lycopene) on breast cancer MCF7 cells, leukemia K562 cells, prostate cancer (LNCaP, DU145, and PC3 cells), and esophageal squamous cancer EC109 cells. PPARγ is the master regulator of adipocyte differentiation and adipogenesis. Downregulated PPARγ and PPARγ-target genes have been associated with the suppressive effects of β-carotene and lycopene on 3T3L1 and C3H10T1/2 adipocyte differentiation and adipogenesis. β-Carotene is cleaved centrally into retinaldehyde by BCO1, the encoding gene being a PPARγ-target gene. Retinaldehyde can be oxidized to retinoic acid and also be reduced to retinol. β-Carotene can also be cleaved asymmetrically into β-apocarotenals and β-apocarotenones by BCO2. The inhibitory effects of β-carotene on the development of adiposity and lipid storage are dependent substantially on BCO1-mediated production of retinoids. The effects of β-carotene on body adiposity were absent in BCO1-knockout mice. Retinoid metabolism is connected with the activity of PPARγ in the control of body-fat reserves. Retinoic acid, retinaldehyde, retinol, and β-apocarotenals exert suppressive effects on preadipocyte differentiation and adipogenesis via downregulation of PPARγ expression in cell culture. The molecular mechanisms underlying retinoic acid effects on adipose-tissue biology and the development of adiposity remain poorly understood. Adiposity can be affected by retinoids through long-lasting effects at critical developmental stages. Retinol saturase increases PPARγ-transcriptional activity and adipocyte differentiation. Other carotenoids that have been reported to suppress adipocyte differentiation and lipid accumulation in the main via modulation of PPARγ and PPARγ-target genes include astaxanthin, bixin, norbixin, β-cryptoxanthin, fucoxanthin and its metabolites, lycopene, apo-10'-lycopenoic acid, siphonaxanthin, and neoxanthin, except paprika pigments. Lutein, lycopene, and paprika carotenoids reduce proinflammatory cytokine levels by an induction of PPARγ in immune tissues and cells. Lycopene, apo-10'-lycopenoic acid, and astaxanthin might prevent atherosclerosis through modifying cholesterol metabolism via increasing PPARγ expression in macrophages.

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The Green Algal Carotenoid Siphonaxanthin Inhibits Adipogenesis in 3T3-L1 Preadipocytes and the Accumulation of Lipids in White Adipose Tissue of KK-Ay Mice

Abstract: These results provide evidence that siphonaxanthin may effectively regulate adipogenesis in 3T3-L1 cells and diabetic KK-Ay mice.

Cited by 45 publications

References 44 publications

Niemann‐Pick C1‐like 1 Promotes Intestinal Absorption of Siphonaxanthin

Niemann‐Pick C1‐like 1 Promotes Intestinal Absorption of Siphonaxanthin

Siphonaxanthin, a Carotenoid From Green Algae, Inhibits Lipogenesis in Hepatocytes via the Suppression of Liver X Receptor α Activity

Role of PPARγ in the nutritional and pharmacological actions of carotenoids

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The Green Algal Carotenoid Siphonaxanthin Inhibits Adipogenesis in 3T3-L1 Preadipocytes and the Accumulation of Lipids in White Adipose Tissue of KK-Ay Mice

Abstract: These results provide evidence that siphonaxanthin may effectively regulate adipogenesis in 3T3-L1 cells and diabetic KK-Ay mice.

Cited by 45 publications

References 44 publications

Niemann‐Pick C1‐like 1 Promotes Intestinal Absorption of Siphonaxanthin

Niemann‐Pick C1‐like 1 Promotes Intestinal Absorption of Siphonaxanthin

Siphonaxanthin, a Carotenoid From Green Algae, Inhibits Lipogenesis in Hepatocytes via the Suppression of Liver X Receptor α Activity

Role of PPAR&gamma; in the nutritional and pharmacological actions of carotenoids

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Role of PPARγ in the nutritional and pharmacological actions of carotenoids