Development of therapies for nonalcoholic fatty liver disease (NALF and NASH) using zebrafish

The project aims to develop and characterize novel zebrafish models of NAFLD induced by a dietary approach, mimicking human disease progression, to identify potential therapeutic targets

Start – End dates: 10/12/18 – 09/12/22

Project reference: Torres Quevedo 2018 (PTQ2018-009785)

Total budget: 150,000€

Financed by: State Research Agency under the Ministry of Science, Innovation and Universities, Spain and the European Union (Next Generation EU)

Financed by MICIU/AEI/10.13039/501100011033.

Partners: Nostrum Biodiscovery & CNAG-CRG, Barcelona


Non-alcoholic fatty liver disease (NAFLD) is a metabolic disease characterized by an increased fat accumulation in the liver without any secondary causes, such as alcohol or drugs, associated. Traditionally, a fat content over 5% is considered a steatoic liver. Importantly, Obesity, the pandemic of our days, significantly increases NAFLD morbidity and the risk of suffering other metabolic-related diseases, such as type 2 diabetes, and cardiovascular diseases. Between 80 to 90% of obese adults will develop hepatic steatosis and 10 to 25 % will develop a more severe disease manifestation, Non-Alcoholic Steatohepatitis (NASH), a life-threatening condition that can cause liver cirrhosis or liver cancer. To date, there are no effective treatments for NAFLD, only dietary therapy has been successful in treating the disease. This lack of effective treatments represents both an important medical need and a huge business opportunity. Therefore, experimental models that can provide fast experimental throughput, and deep biological information to explain complex multi-organ diseases, are needed. In this context, the Zebrafish, which shares remarkable resemblances with humans in lipid metabolism, and adipogenic pathways, is an ideal tool to study the progression of NAFLD. In this study, a novel dietary approach to induce NAFLD in juvenile zebrafish has been set up and characterized. Also, genetics modes have been developed and are under characterization. The novel dietary models display increases in body mass index (BMI), fat accumulation in the abdominal area, and hepatic steatosis when treated with hyper-caloric diets. In the same way, altered values in cholesterol, triglycerides, glucose, and hepatic enzymes are observed. These results, highly resemble alterations observed in NAFLD patients, validating this dietary model in zebrafish to study the disease’s progression and possible therapeutic targets for NAFLD.