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Metabolic Disorders and Obesity Model

Obesity is a disease that involves excessive body fat and a Body Mass Index (BMI) > 30. It increases the risk of suffering several metabolic-related diseases such as type 2 diabetes, cardiovascular diseases, and non-alcoholic fatty liver disease (NAFLD).

Obesity goes along with many alterations that give rise to the so-called metabolic syndrome, such as insulin resistance, liver fat, high blood pressure, heart problems, and atherosclerosis. Abdominal fat accumulation is a key marker in obese patients since it correlates especially well with these metabolic and cardiovascular symptoms.

Zebrafish share remarkable genetic, anatomic, and functional similarities with humans in lipid metabolism, adipogenic pathways, and the presence of all key organs required for lipid metabolism. This high conservation makes zebrafish a valuable model for understanding the mechanisms of obesity and metabolic diseases.

Feeding zebrafish a High-Fat (HF), High-Fat Carbohydrates (HFC), or Extra Feeding (EF) diets results in an increase in visceral fat and BMI, and liver steatosis.

As a leading preclinical CRO in the metabolic field using zebrafish, ZeClinics offers obesity preclinical CRO services to help our clients to accelerate the validation of their gene candidates. They can take advantage of our diet-induced adult and juvenile zebrafish models, which recapitulate the key aspects of obesity, and represent an efficient and cost-effective option to study this condition.

Applications

  • Study the impact of nutritional interventions on fat accumulation and distribution and on BMI.
  • Genetic functional studies of potential obesity-modulating genes (target validation).

Advantages

Lipid metabolism and adipogenic pathways in zebrafish and humans are remarkably similar.

Transparent zebrafish larvae facilitate in vivo liver fat quantification via non-invasive imaging.

Rapid induction of obesity key markers with short dietary interventions.

In vivo model suitable for obtaining valuable insights on complex metabolic processess.

Method description

Juvenile approach

Juvenile zebrafish are fed a Control Diet (CD) versus HFC diet for 10 days in the desired genetic background. Individuals are measured and weighted for BMI calculation, incubated with a fluorescent dye for evaluation of fat accumulation and distribution, and finally stained for liver steatosis quantification. This study can be complemented with metabolic evaluations such as glucose, cholesterol, or triglycerides.

Adult approach

Adult zebrafish are fed a Control Diet (CD) versus HFC for 8 weeks in the desired genetic background. Individuals are measured and weighted for BMI calculation, incubated with a fluorescent dye for evaluation of fat accumulation and distribution, and finally stained for liver steatosis quantification. This study can be complemented with metabolic evaluations such as glucose, cholesterol, or triglycerides.

Readouts

  • Body length
  • Body weight
  • Body Mass Index (BMI)
  • Lipid accumulation and distribution (visceral fat): total adipose tissue area and abdominal fat accumulation can be assessed with fluorescent lipid dye.
  • Hepatic steatosis: fat accumulation in the liver.

Optionally:

  • Hepatic enzymes
  • Triglycerides quantification
  • Glucose quantification
  • Cholesterol quantification
Figure 1. Juvenile obesity model. A) Protocol summary. Fish are fed for 10 days with a Control Diet (CD), or High-Fat Carbohydrates diet (HFC). B) Length, weight, and Body Mass Index (BMI). Fish fed a HFC show higher body length, weight and BMI when compared to CD-fed fish. Means and SEM are plotted. *** p<0.001 vs CD.
Figure 2. Lipid accumulation model in juvenile fish. Fish are fed for 10 days with a Control Diet (CD), or High-Fat Carbohydrates diet (HFC). A) Staining of fish adipocytes with a fluorescent dye for evaluation of fat accumulation and distribution. Abdominal fat accumulation is observed in fish fed with HFC. B) Abdominal fat quantification. Fluorescence intensity measurement was done in the individual under different diets. Statistical analyses have shown significant differences between CD and HFC. Means and eSEM are plotted. ***p<0.001 vs CD.

References

  1. Brahe LK, Astrup A, Larsen LH. Can We Prevent Obesity-Related Metabolic Diseases by Dietary Modulation of the Gut Microbiota? Adv Nutr. 2016 Jan 15;7(1):90-101.
  2. Faillaci F, Milosa F, Critelli RM, Turola E, Schepis F, Villa E. Obese zebrafish: A small fish for a major human health condition. Animal Model Exp Med. 2018 Nov 21;1(4):255-265.
  3. Zang L, Maddison LA, Chen W. Zebrafish as a Model for Obesity and Diabetes. Front Cell Dev Biol. 2018 Aug 20;6:91.