Zebrafish Obesity Models

Obesity is a major risk factor for diabetes, cardiovascular disease, cancer, sleep apnea, nonalcoholic fatty liver disease, osteoarthritis, and other diseases, and is associated with disability, mortality, and health costs. Therefore, excellent animal models of obesity are essential to better understand the development of metabolic dysfunction and the development of anti-obesity drugs.

Multiple studies have demonstrated that zebrafish are an excellent model for studying metabolic dysfunction, as zebrafish possess key organs important for regulating energy homeostasis and metabolism in mammals, including digestive organs, adipose tissue, and skeletal muscle. Similar to mammals, excess nutrients in zebrafish lead to elevated plasma triglyceride levels and hepatic steatosis. The highly conserved distribution and formation of adipose tissue in zebrafish compared to mammals makes it a suitable model for studying obesity. Obese zebrafish also exhibit dysregulation of pathways that control lipid metabolism, including SREBF1, PPAR, NR1H3, and LEP. These metabolic pathways play key roles in adipocyte differentiation, energy homeostasis, and cholesterol metabolism, and their protection proves that zebrafish is a suitable model for human lipid metabolism.

3D micro-CT analysis of normally-fed and obese-fed zebrafish.

Our Zebrafish Obesity Models

Food-induced zebrafish obesity models

Treatment	Zebrafish Age	Characteristics
Heavy whipping cream	Larvae	Lipid accumulation in intersegmental vessels; increased whole-larval triacylglycerol (TAG) and apolipoprotein B levels
Chicken egg yolk	Larvae, juvenile, adult	Hyperlipidemia, increased adipose tissue area and TAG
Corn oil and lard	Adult	Increased body fat
Artemia	Adult	Increased BMI, hypertriglyceridemia and hepatosteatosis
Tetramin and vegetable oil	Juvenile, adult	Increased weight gain, cardiovascular overload
Artemia and egg yolk powder	Adult	Increased body weight, adipose tissue mass, adipocyte hypertrophy, hyperglycemia and hepatosteatosis

Transgenic zebrafish obesity models

Genetic manipulation	Zebrafish Age	Characteristics
Overexpression of agrp	All stages	Increased linear growth, adipocyte hypertrophy
miR-27b depletion	All stages	Hyperlipidemia, hepatic steatosis and increased white adipose tissue mass
Overexpression of akt1	All stages	Increased BMI, adipocyte hyperplasia, abnormal fat deposition, and glucose intolerance

Mutant zebrafish obesity models

Genetic manipulation	Zebrafish Age	Characteristics
Mutation in trappc11	Larvae	Hepatomegaly and steatosis
Mutation in cdipt	Larvae	Hepatic steatosis
Mutation in gfpt1	Larvae	Increased whole body TAG and hepatic steatosis
Mutation in vmp1	Larvae	Hepatic steatosis
Mutation in achy	Larvae	Mitochondrial dysfunction, hepatic steatosis, and disrupted exocrine pancreas
Mutation in slc16a6a	Larvae	Fasting hepatic steatosis
Mutation in gh1	Larvae, adult	Decreased somatic growth, increased accumulation of adipose tissue
cyp2r1 mutations	Adult	Growth retardation, increased adiposity
Mutation in plxnd1	Adult	Disproportional SAT, altered body fat distribution after high-fat feeding, protected from insulin resistance

The zebrafish models we provide enable rapid identification of chemical and genetic modifiers of phenotype, which serves as an attractive model system for assessing the effects of functional foods and compounds on obesity development and treatment.We also offer a range of zebrafish obesity model test systems to advance your drug candidates from discovery to IND. Contact us today to discuss your goals and how we can achieve them.

References

Zang L, et al. Zebrafish as a Model for Obesity and Diabetes. Frontiers in cell and developmental biology. 2018, 6:91.
Dooley K, et al. Zebrafish: a model system for the study of human disease.Curr Opin Genet Dev. 2000, 10(3):252-6.
Hasumura T, et al. Green tea extract suppresses adiposity and affects the expression of lipid metabolism genes in diet-induced obese zebrafish. Nutr Metab (Lond). 2012, 9(1):73.

For research use only. Not intended for any clinical use.