Dataset Information

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

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 ?-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.

SUBMITTER: Tainaka T

PROVIDER: S-EPMC3275548 | biostudies-literature | 2011 Dec

REPOSITORIES: biostudies-literature

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

Tainaka Toshiyuki T Shimada Yasuhito Y Kuroyanagi Junya J Zang Liqing L Oka Takehiko T Nishimura Yuhei Y Nishimura Norihiro N Tanaka Toshio T

Nutrition & metabolism 20111213

<h4>Background</h4>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.<h4>Results ...[more]

PMID: 22152339

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Project description:Background: The prevalence of non-alcohol fatty liver disease (NAFLD) is increasing in children and adolescents who are mostly resulted from overfeeding. Previous studies demonstrate that berberine (BBR), a compound derived from plant, has beneficial effects on NAFLD in adults but poorly understood in the pediatric population. This study employed a larval zebrafish model to mimic the therapeutic effects of BBR in the pediatric population and the mechanisms underlying its hepatoprotection. Methods: High-cholesterol diet (HCD)-fed zebrafish exposed to BBR at doses of 0, 1, 5, and 25 μM. After the larvae were treated with BBR for 10 days, its effect on hepatic steatosis was evaluated. We introduced Raman imaging and three-dimensional (3D) molecular imaging to detect changes in the biochemical composition and reactive oxygen species (ROS) levels of zebrafish liver. Gene expression microarray was performed to identify differentially expressed genes (DEGs) followed by gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and functional category analysis. Results: BBR (5 and 25 μM) administration prevented HCD-induced liver lipid accumulation in larval zebrafish. The result was further confirmed by the pathological observation. Raman mapping indicated that the biochemical composition in the liver of BBR-treated group shifted to the control. The quantitative analysis of 3D imaging showed that the ROS level was significantly decreased in the liver of BBR-treated larvae. In the livers of the BBR group, we found 468 DEGs, including 172 genes with upregulated expression and 296 genes with downregulated expression. Besides, GO enrichment, KEGG pathway, and functional category analysis showed that various processes related to glucolipid metabolism, immune response, DNA damage and repair, and iron were significantly enriched with DEGs. The expression levels of the crucial genes from the functional analysis were also confirmed by quantitative PCR (qPCR). Conclusion: BBR can significantly improve hepatic steatosis in HCD-fed zebrafish larvae. Its mechanisms might be associated with the regulation of lipid metabolism, oxidative stress, and iron homeostasis. Raman imaging in larval zebrafish might become a useful tool for drug evaluation. Mainly, the gene expression profiles provide molecular information for BBR on the prevention and treatment of pediatric NAFLD.

Project description:Blue honeysuckle (BH, Lonicera caerulea) is used as a traditional medicine in Russia, Japan and China, but is not commonly considered as an edible berry in Europe, USA or Korea. BH has been revealed to decrease serum cholesterol and triacylglycerol (triglyceride or TG) levels through the activation of AMP‑activated protein kinase (AMPK), thus it is expected to be a health functional food and pharmaceutical agent for the prevention of non‑alcoholic liver damage, in addition to effects as a suppressor of hyperlipidemia and as an anti‑obesity agent. In the present study, the pharmacological activity of BH extract (BHe) was observed in high‑fat diet (HFD)‑fed mice. Significant increases in fat pad weight, body weight, fat accumulation (body and abdominal fat density, and thickness of the periovarian and abdominal wall) and serum biochemical levels (aspartate transaminase, alanine aminotransferase, alkaline phosphatase, lactate dehydrogenase, γ‑glutamyltransferase, total cholesterol, low‑density lipoprotein and TG, with the exception of high‑density lipoprotein) were observed in HFD‑fed mice. In addition, increases in adipocyte hypertrophy, the area of steatohepatitis and hepatocyte hypertrophy were observed, whereas decreased zymogen content was identified upon histopathological observation. Increased deterioration of the endogenous antioxidant defense system (liver catalase, glutathione and superoxide dismutase) and hepatic lipid peroxidation was observed. In addition, there were decreases in hepatic glucokinase activity, AMPKα1 and AMPKα2 mRNA expression, adipose tissue uncoupling protein 2 expression, and adiponectin mRNA expression, increases in phosphoenolpyruvate carboxykinase and glucose‑6‑phosphatase activity, hepatic acetyl‑CoA carboxylase 1 mRNA expression, and the expression of leptin, CCAAT/enhancer‑binding protein (C/EBP) α, C/EBPβ and sterol‑regulatory‑element‑binding protein 1c mRNA in the periovarian tissue. Furthermore, non‑alcoholic fatty liver disease (NAFLD) and obesity were significantly inhibited by the continuous administration of BHe for 84 days. These results revealed that BHe may be a promising novel drug or functional food candidate for the treatment of obesity and NAFLD.

Dataset Information

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

Publications

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

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