ZeEfficacy – Efficacy Services

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Non-Alcoholic Fatty Liver Disease (NAFLD) model

Non-alcoholic fatty liver disease (NAFLD) is the term for a range of conditions caused by a buildup of fat in the liver cells (Non-alcoholic fatty liver). It's usually seen in people who are overweight or obese. If it is not detected and managed at early stages, it can progress to non-alcoholic steatohepatitis (NASH), a more serious form of NAFLD, where the liver has become inflamed and the liver cells injured, and even lead to fibrosis, cirrhosis, and finally liver failure. 

Zebrafish fat metabolism is highly conserved with humans. Indeed, zebrafish express all main nuclear receptors, lipid transporters, apolipoproteins, and enzymes involved in lipoprotein metabolism. Even the activity of the cholesteryl ester transfer protein (CETP), which is naturally deficient in rodents, is detected in zebrafish plasma.

Feeding zebrafish a High Cholesterol diet  (HC) results in a significantly increased fat liver (steatosis), which makes zebrafish an attractive model to study lipid metabolism and human NAFLD condition.

We offer a diet-based disease model for the study of liver fat metabolism and disease mechanisms of NAFLD condition, with a biologically relevant, cost-effective, and fast approach.

Applications

  • Study the impact of nutritional interventions on liver physiology and the development of NAFLD.
  • Perform gene candidate screening for NAFLD.
  • Screening of potential lipid-regulatory molecules that may be therapeutic candidates for NAFLD.

Advantages

Fat metabolism in zebrafish and humans is remarkably similar.

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

High throughput screening of molecules.

Method description

Early-life embryos (5 dpf) are fed a Control Diet (CD) versus a HC diet and Extra Feeding diet (EF) for 10 days in the presence and absence of the compound of interest. Lipid staining is then performed to quantify the liver fat accumulation of zebrafish larvae.

Readouts

  • Hepatic steatosis: fat accumulation in the liver.
  • Liver function: can be assessed with enzymatic markers.
Figure 1. Hepatic steatosis. A) Representative images of liver fat accumulation in zebrafish larvae after Control Diet (CD), High Cholesterol diet (HC), and Extra Feeding diet (EF). B) Quantification of steatosis as negative, mild, or severe according to the fish fraction of fat accumulation in zebrafish larvae fed a CD vs. HC and EF.