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.

Obesity and diabetes now considered global epidemics. The prevalence rates of diabetes are increasing in parallel with the rates of obesity and the strong connection between these two diseases has been coined as “diabesity.” The health risks of overweight or obesity include Type 2 diabetes mellitus (T2DM), coronary heart disease and cancer of numerous organs. Both obesity and diabetes are complex diseases that involve the interaction of genetics and environmental factors. The underlying pathogenesis of obesity and diabetes are not well understood and further research is needed for pharmacological and surgical management. Consequently, the use of animal models of obesity and/or diabetes is important for both improving the understanding of these diseases and to identify and develop effective treatments. Zebrafish is an attractive model system for studying metabolic diseases because of the functional conservation in lipid metabolism, adipose biology, pancreas structure, and glucose homeostasis. It is also suited for identification of novel targets associated with the risk and treatment of obesity and diabetes in humans. In this review, we highlight studies using zebrafish to model metabolic diseases, and discuss the advantages and disadvantages of studying pathologies associated with obesity and diabetes in zebrafish.

Obesity is a major cause of type 2 diabetes mellitus (T2DM) in mammals. We have previously established a zebrafish model of diet-induced obesity (DIO zebrafish) by overfeeding Artemia. Here we created DIO zebrafish using a different method to induce T2DM. Zebrafish were overfed a commercially available fish food using an automated feeding system. We monitored the fasting blood glucose levels in the normal-fed group (one feed/day) and overfed group (six feeds/day) over an 8-week period. The fasting blood glucose level was significantly increased in DIO zebrafish compared with that of normal-fed zebrafish. Intraperitoneal and oral glucose tolerance tests showed impaired glucose tolerance by overfeeding. Insulin production, which was determined indirectly by measuring the EGFP signal strength in overfed Tg(−1.0ins:EGFP) sc1 zebrafish, was increased in DIO zebrafish. The anti-diabetic drugs metformin and glimepiride ameliorated hyperglycaemia in the overfed group, suggesting that this zebrafish can be used as a model of human T2DM. Finally, we conducted RNA deep sequencing and found that the gene expression profiling of liver-pancreas revealed pathways common to human T2DM. In summary, we developed a zebrafish model of T2DM that shows promise as a platform for mechanistic and therapeutic studies of diet-induced glucose intolerance and insulin resistance.

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