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Transcriptome analysis of anti-fatty liver action by Campari tomato using a zebrafish diet-induced obesity model.

Tainaka T, Shimada Y, Kuroyanagi J, Zang L, Oka T, Nishimura Y, Nishimura N, Tanaka T - Nutr Metab (Lond) (2011)

Bottom Line: We focused on "Campari" tomato, which suppressed increase of body weight, plasma TG, and lipid droplets in livers of DIO-zebrafish.Campari tomato decreased srebf1 mRNA by increase of foxo1 gene expression, which may depend on high contents of β-carotene in this strain.DIO-zebrafish can discriminate the anti-obesity effects of different strains of vegetables, and will become a powerful tool to assess outcomes and find novel mechanisms of anti-obesity effects of natural products.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Molecular and Cellular Pharmacology, Pharmacogenomics and Pharmacoinformatics, Mie University Graduate School of Medicine, Mie, Japan. tanaka@doc.medic.mie-u.ac.jp.

ABSTRACT

Background: High dietary intake of vegetable products is beneficial against obesity and its related diseases such as dyslipidemia, nonalcoholic fatty liver disease, and cancer. We previously developed a diet-induced obesity model of zebrafish (DIO-zebrafish) that develops visceral adiposity, dyslipidemia, and liver steatosis. Zebrafish is a polyphagous animal; thus we hypothesized that DIO-zebrafish could be used for transcriptome analysis of anti-obesity effects of vegetables.

Results: Each vegetable exhibited different effects against obesity. We focused on "Campari" tomato, which suppressed increase of body weight, plasma TG, and lipid droplets in livers of DIO-zebrafish. Campari tomato decreased srebf1 mRNA by increase of foxo1 gene expression, which may depend on high contents of β-carotene in this strain.

Conclusions: Campari tomato ameliorates diet-induced obesity, especially dyslipidemia and liver steatosis via downregulation of gene expression related to lipogenesis. DIO-zebrafish can discriminate the anti-obesity effects of different strains of vegetables, and will become a powerful tool to assess outcomes and find novel mechanisms of anti-obesity effects of natural products.

No MeSH data available.


Related in: MedlinePlus

Lycopene effects on body weight, plasma TG, and hepatic steatosis in DIO-zebrafish. (A) Average body weight in each group during 4-week feeding experiments. Values are mean ± SD. Each group contained 20 samples. *P < 0.05; **P < 0.01 vs. vehicle with overfeeding, black circles. (B) Change of plasma TG levels in each group. *P < 0.05 vs. vehicle with overfeeding. (C) Oil red O staining of liver sections.
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Figure 2: Lycopene effects on body weight, plasma TG, and hepatic steatosis in DIO-zebrafish. (A) Average body weight in each group during 4-week feeding experiments. Values are mean ± SD. Each group contained 20 samples. *P < 0.05; **P < 0.01 vs. vehicle with overfeeding, black circles. (B) Change of plasma TG levels in each group. *P < 0.05 vs. vehicle with overfeeding. (C) Oil red O staining of liver sections.

Mentions: Compared with flake foods that have also been used to feed zebrafish [13] the amounts of fat and protein in Artemia are higher and lower, respectively, whereas the amount of carbohydrate is comparable [24]. Zebrafish fed 5 or 60 mg of freshly hatched Artemia daily consumed about 80% and 50% of the provided Artemia, respectively, translating to 20 and 150 cal, respectively. Since maintenance energy requirement for zebrafish is < 30 cal [25], it seems reasonable to induce DIO-zebrafish by this overfeeding protocol. After 2 weeks, increases of body weight and plasma TG were noted (Additional file 3, Table S2). In all experiments, overfed fish significantly increased body weight and plasma TG in comparison with normal feeding group (P < 0.01), indicating that DIO-zebrafish was well constructed. Eggplant of the "Choshi" strain showed a trend towards suppression of the diet-induced body weight increase (P < 0.1) and significantly reduced the increase in plasma TG (P < 0.05). The Choshi strain is a darker eggplant, and contains more anthocyanins than the Senryo strain (data not shown). Anthocyanins have been reported to normalize the lipid parameters in a high fat diet-induced mouse model of obesity [26], and we hypothesize that the same mechanism may be occurring in DIO-zebrafish fed Choshi eggplant-containing food. Campari strain tomato, on the other hand, dramatically suppressed increase of body weight and plasma TG in overfed fish, to almost those of normal feeding fish, in both 2- and 4-week feeding experiments (Additional file 3, Table S2, Figure 1B and 1C). However, the fasting blood glucose did not significantly differ between the Campari-fed group and the controls (Additional file 4, Figure S2). There was no appetite suppression by Campari tomato during the feeding experiment (Figure 1D). Campari tomato reduced lipid accumulation (numbers and size of red spots) of liver tissues more than overfeeding with regular tomato (Figure 1E), corresponding to the results of plasma TG lowering. In addition, since the OF fish that were fed Campari tomato-containing food ate almost the same number of calories as those in the other two OF groups, but gained less body weight, we hypothesized that their energy expenditure must be increased. In fact, genes involved in fatty acid oxidation such as peroxisome proliferator-activated receptor gamma coactivator 1α (ppargc1a-like, a zebrafish homolog of human PPARGC1A, also called PGC-1α) and peroxisome proliferator-activated receptor αb (ppar-ab), were also increased in OF Campari tomato-fed fish in comparison to OF controls (Figure 1F and 1G). Lycopene, the pigment that gives tomatoes their red colour, may play a role in preventing diseases related to obesity including dyslipidemia [14-16]. Campari tomatoes contain more lycopene than regular tomatoes (Table 1). This results in their high antioxidant activity, as measured by their DPPH radical scavenging activity (Additional file 5, Figure S3). In a preliminary experiment 4-week administration of lycopene at a volume based on the amount in Campari tomatoes (0.74 μg/mg diet) slightly and nonsignificantly decreased weight gain (Figure 2A) and plasma TG (Figure 2B) and did not improve hepatic steatosis and visceral fat deposition (Figure 2C). Campari tomato was more protective than lycopene alone in DIO-zebrafish, consistent with previous reports that tomato powder administration is more efficacious than lycopene supplement against serum TG elevation and lipid peroxidation in oxidative stress model of rat [27]. Lipid peroxidation is highly related to nonalcoholic steatosis and steatohepatitis in human [28] and our model of DIO-zebrafish probably contains the same mechanism. Tomato contains vitamins A, C, and E and several carotenoids such as α-, β-, and γ-carotenes, luteins, phytoene, and phytofluene [29-31]. Many of these nutrients have antioxidant property and in combination with lycopene may contribute to protect against lipid peroxidation. On the other hand, Ali et al. [27] reported that when tomato was fed to rats only lycopene and β-carotene were detected their liver tissues.


Transcriptome analysis of anti-fatty liver action by Campari tomato using a zebrafish diet-induced obesity model.

Tainaka T, Shimada Y, Kuroyanagi J, Zang L, Oka T, Nishimura Y, Nishimura N, Tanaka T - Nutr Metab (Lond) (2011)

Lycopene effects on body weight, plasma TG, and hepatic steatosis in DIO-zebrafish. (A) Average body weight in each group during 4-week feeding experiments. Values are mean ± SD. Each group contained 20 samples. *P < 0.05; **P < 0.01 vs. vehicle with overfeeding, black circles. (B) Change of plasma TG levels in each group. *P < 0.05 vs. vehicle with overfeeding. (C) Oil red O staining of liver sections.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3275548&req=5

Figure 2: Lycopene effects on body weight, plasma TG, and hepatic steatosis in DIO-zebrafish. (A) Average body weight in each group during 4-week feeding experiments. Values are mean ± SD. Each group contained 20 samples. *P < 0.05; **P < 0.01 vs. vehicle with overfeeding, black circles. (B) Change of plasma TG levels in each group. *P < 0.05 vs. vehicle with overfeeding. (C) Oil red O staining of liver sections.
Mentions: Compared with flake foods that have also been used to feed zebrafish [13] the amounts of fat and protein in Artemia are higher and lower, respectively, whereas the amount of carbohydrate is comparable [24]. Zebrafish fed 5 or 60 mg of freshly hatched Artemia daily consumed about 80% and 50% of the provided Artemia, respectively, translating to 20 and 150 cal, respectively. Since maintenance energy requirement for zebrafish is < 30 cal [25], it seems reasonable to induce DIO-zebrafish by this overfeeding protocol. After 2 weeks, increases of body weight and plasma TG were noted (Additional file 3, Table S2). In all experiments, overfed fish significantly increased body weight and plasma TG in comparison with normal feeding group (P < 0.01), indicating that DIO-zebrafish was well constructed. Eggplant of the "Choshi" strain showed a trend towards suppression of the diet-induced body weight increase (P < 0.1) and significantly reduced the increase in plasma TG (P < 0.05). The Choshi strain is a darker eggplant, and contains more anthocyanins than the Senryo strain (data not shown). Anthocyanins have been reported to normalize the lipid parameters in a high fat diet-induced mouse model of obesity [26], and we hypothesize that the same mechanism may be occurring in DIO-zebrafish fed Choshi eggplant-containing food. Campari strain tomato, on the other hand, dramatically suppressed increase of body weight and plasma TG in overfed fish, to almost those of normal feeding fish, in both 2- and 4-week feeding experiments (Additional file 3, Table S2, Figure 1B and 1C). However, the fasting blood glucose did not significantly differ between the Campari-fed group and the controls (Additional file 4, Figure S2). There was no appetite suppression by Campari tomato during the feeding experiment (Figure 1D). Campari tomato reduced lipid accumulation (numbers and size of red spots) of liver tissues more than overfeeding with regular tomato (Figure 1E), corresponding to the results of plasma TG lowering. In addition, since the OF fish that were fed Campari tomato-containing food ate almost the same number of calories as those in the other two OF groups, but gained less body weight, we hypothesized that their energy expenditure must be increased. In fact, genes involved in fatty acid oxidation such as peroxisome proliferator-activated receptor gamma coactivator 1α (ppargc1a-like, a zebrafish homolog of human PPARGC1A, also called PGC-1α) and peroxisome proliferator-activated receptor αb (ppar-ab), were also increased in OF Campari tomato-fed fish in comparison to OF controls (Figure 1F and 1G). Lycopene, the pigment that gives tomatoes their red colour, may play a role in preventing diseases related to obesity including dyslipidemia [14-16]. Campari tomatoes contain more lycopene than regular tomatoes (Table 1). This results in their high antioxidant activity, as measured by their DPPH radical scavenging activity (Additional file 5, Figure S3). In a preliminary experiment 4-week administration of lycopene at a volume based on the amount in Campari tomatoes (0.74 μg/mg diet) slightly and nonsignificantly decreased weight gain (Figure 2A) and plasma TG (Figure 2B) and did not improve hepatic steatosis and visceral fat deposition (Figure 2C). Campari tomato was more protective than lycopene alone in DIO-zebrafish, consistent with previous reports that tomato powder administration is more efficacious than lycopene supplement against serum TG elevation and lipid peroxidation in oxidative stress model of rat [27]. Lipid peroxidation is highly related to nonalcoholic steatosis and steatohepatitis in human [28] and our model of DIO-zebrafish probably contains the same mechanism. Tomato contains vitamins A, C, and E and several carotenoids such as α-, β-, and γ-carotenes, luteins, phytoene, and phytofluene [29-31]. Many of these nutrients have antioxidant property and in combination with lycopene may contribute to protect against lipid peroxidation. On the other hand, Ali et al. [27] reported that when tomato was fed to rats only lycopene and β-carotene were detected their liver tissues.

Bottom Line: We focused on "Campari" tomato, which suppressed increase of body weight, plasma TG, and lipid droplets in livers of DIO-zebrafish.Campari tomato decreased srebf1 mRNA by increase of foxo1 gene expression, which may depend on high contents of β-carotene in this strain.DIO-zebrafish can discriminate the anti-obesity effects of different strains of vegetables, and will become a powerful tool to assess outcomes and find novel mechanisms of anti-obesity effects of natural products.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Molecular and Cellular Pharmacology, Pharmacogenomics and Pharmacoinformatics, Mie University Graduate School of Medicine, Mie, Japan. tanaka@doc.medic.mie-u.ac.jp.

ABSTRACT

Background: High dietary intake of vegetable products is beneficial against obesity and its related diseases such as dyslipidemia, nonalcoholic fatty liver disease, and cancer. We previously developed a diet-induced obesity model of zebrafish (DIO-zebrafish) that develops visceral adiposity, dyslipidemia, and liver steatosis. Zebrafish is a polyphagous animal; thus we hypothesized that DIO-zebrafish could be used for transcriptome analysis of anti-obesity effects of vegetables.

Results: Each vegetable exhibited different effects against obesity. We focused on "Campari" tomato, which suppressed increase of body weight, plasma TG, and lipid droplets in livers of DIO-zebrafish. Campari tomato decreased srebf1 mRNA by increase of foxo1 gene expression, which may depend on high contents of β-carotene in this strain.

Conclusions: Campari tomato ameliorates diet-induced obesity, especially dyslipidemia and liver steatosis via downregulation of gene expression related to lipogenesis. DIO-zebrafish can discriminate the anti-obesity effects of different strains of vegetables, and will become a powerful tool to assess outcomes and find novel mechanisms of anti-obesity effects of natural products.

No MeSH data available.


Related in: MedlinePlus