Abstract

BackgroundObesity is a multifactorial disorder influenced by genetic and environmental factors. Animal models of obesity are required to help us understand the signaling pathways underlying this condition. Zebrafish possess many structural and functional similarities with humans and have been used to model various human diseases, including a genetic model of obesity. The purpose of this study was to establish a zebrafish model of diet-induced obesity (DIO).ResultsZebrafish were assigned into two dietary groups. One group of zebrafish was overfed with Artemia (60 mg dry weight/day/fish), a living prey consisting of a relatively high amount of fat. The other group of zebrafish was fed with Artemia sufficient to meet their energy requirements (5 mg dry weight/day/fish). Zebrafish were fed under these dietary protocols for 8 weeks. The zebrafish overfed with Artemia exhibited increased body mass index, which was calculated by dividing the body weight by the square of the body length, hypertriglyceridemia and hepatosteatosis, unlike the control zebrafish. Calorie restriction for 2 weeks was applied to zebrafish after the 8-week overfeeding period. The increased body weight and plasma triglyceride level were improved by calorie restriction. We also performed comparative transcriptome analysis of visceral adipose tissue from DIO zebrafish, DIO rats, DIO mice and obese humans. This analysis revealed that obese zebrafish and mammals share common pathophysiological pathways related to the coagulation cascade and lipid metabolism. Furthermore, several regulators were identified in zebrafish and mammals, including APOH, IL-6 and IL-1β in the coagulation cascade, and SREBF1, PPARα/γ, NR1H3 and LEP in lipid metabolism.ConclusionWe established a zebrafish model of DIO that shared common pathophysiological pathways with mammalian obesity. The DIO zebrafish can be used to identify putative pharmacological targets and to test novel drugs for the treatment of human obesity.

Highlights

  • Obesity is a multifactorial disorder influenced by genetic and environmental factors

  • Zebrafish overfed with Artemia become obese To develop a zebrafish model of diet-induced obesity (DIO), we overfed the fish with freshly hatched nauplii of brine shrimp Artemia, a common food source for aquaculture [24]

  • Given the hierarchy of macronutrient effects on the perception of hunger, it is plausible that zebrafish would overfeed on Artemia and become obese

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Summary

Introduction

Obesity is a multifactorial disorder influenced by genetic and environmental factors. Numerous studies in rodents have attempted to characterize the functions of obesity-related genes and whole-animal responses to high-calorie and high-fat diets [7]. Such studies have generally shown that the obesity phenotype can differ based on the functions of knockout genes, genetic background, and dietary protocols [6,7,8,9,10]. This suggests the importance of developing and analyzing genetic and diet-induced models of obesity

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