Research Article: Resveratrol ameliorates diet-induced dysregulation of lipid metabolism in zebrafish (Danio rerio)

Date Published: July 7, 2017

Publisher: Public Library of Science

Author(s): Gai Ran, Li Ying, Lin Li, Qiaoqiao Yan, Weijie Yi, Chenjiang Ying, Hongmei Wu, Xiaolei Ye, Kaushik Biswas.


Defective lipid metabolism is associated with increased risk of various chronic diseases, such as obesity, cardiovascular diseases, and diabetes. Resveratrol (RSV), a natural polyphenol, has been shown the potential of ameliorating disregulations of lipid metabolism. The objective of this study was to investigate the effects of feed intake and RSV on lipid metabolism in zebrafish (Danio rerio). The adult males were randomly allocated to 6 groups: control (Con, 8 mg cysts/fish/day), control with 20 μmol/L RSV (Con+RSV), calorie restriction (CR, 5 mg cysts/fish/day), calorie restriction with RSV (CR+RSV), overfeed (OF, 60 mg cysts/fish/day), and overfeed with RSV (OF+RSV) groups. The treatment period was 8 weeks. Results showed that CR reduced body length, body weight, and condition factor of zebrafish. CR reduced levels of plasma triglyceride (TG) and induced protein expression of phosphorylated AMP-activated protein kinase-α (pAMPKα), silent information regulator 2 homolog 1 (Sirt1), and peroxisome proliferator activated receptor gamma coactivator-1α (PGC1α). RSV attenuated CR-induced pAMPKα/AMPKαincreases. RSV increased levels of Sirt1 protein in the OF zebrafish, and decreased OF-induced increase in peroxisome proliferator-activated receptor-γ (PPARγ) protein level. Additionally, RSV down-regulated caveolin-1 and up-regulated microtubule-associated protein 1 light chain 3 -II (LC3-II) protein levels in OF zebrafish. In conclusion, these results suggest that 1) CR reduces plasma TG level through activation of the AMPKα-Sirt1- PGC1α pathway; 2) under different dietary stress conditions RSV might regulate AMPK phosphorylation bi-directionally; 3) RSV might regulate lipid metabolism through the AMPKα-Sirt1-PPARγ pathway in OF zebrafish.

Partial Text

Differences in calorie intake contribute to the formation of various somatotypes that affect optimal health. High-fat diet enhances an excess of energy intake, resulting in excessive fat accumulation and an increased risk of acquiring a number of chronic diseases, such as obesity, cardiovascular diseases, and diabetes [1]. Conversely, calorie restriction (CR), a 30%–50% reduction in dietary intake relative to ad libitum, has been proven to be effective in extending lifespan and protecting against obesity, cardiovascular disease, and diabetes in various animal models, such as fish, rats and mice [2, 3].

In the present study, the effects of feed intake and RSV and the potential regulatory pathways have been investigated in zebrafish. Three levels of calorie intake, including normal (control), calorie restriction and overfeeding are applied. The energy requirement of zebrafish is 30 calories per day [26]. One mg artemia may provide 5 calories, and the consumption of artemia is about 80% [23]; therefore, eight mg cysts/fish/day is provided for control groups to meet the energy demands. For CR groups, five mg cysts/fish/day (around 60% of the control group) is provided. For overfeeding groups, 60 mg cysts/fish/day is provided referring to the literature [27].




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