Protective effect of fish oil targeting hadhaa (3-ketoacyl-CoA thiolase, alpha subunit a and hadhb (3-ketoacyl-CoA thiolase, beta subunit) against high cholesterol diet (HCD) induced atherosclerosis on Zebrafish

Abstract

Currently a high mortality rate is observed due to heart diseases such as atherosclerosis and myocardial infarction, which are mainly caused due to high cholesterol. More novel drugs are needed to replace the currently available drugs to reduce the side effects. Zebrafish are an effective model for lipid metabolism studies in vertebrates. Because it shares 80% of diseases related genes similarity with humans. Zebrafish (Male) were fed with high cholesterol diet to induce atherosclerosis and the cholesterol levels of the Zebrafish are measured. Further, the m RNA expression of hadhaa and hadhb genes in the liver, intestine, and skeletal muscle of Zebrafish are studied. Finally, the atherosclerotic protective effects of fish oil are studied using fluorescence imaging of EGPF Zebrafish larvae and using nail red staining. In this study, we evaluated the effect of a fish oil-rich diet, dietary lipids reported having anti-obesity effects in animals, or cholesterol build-up in Zebrafish. Zebrafish were fed a high cholesterol diet containing 20% (w/w) fish oil. Zebrafish in the fish oil-fed group has 40% less cholesterol build-up than in the regular diet group. The genes encoding beta oxidases such as hadhaa and hadhb are expressed 2 fold higher in the gut of the fish oil treated group. Thiolase/enoyl coenzyme A-hydrates were 20% higher in the test (fish oil) diet group than in the normal diet (pellets) group (p < 0.05). The expression of the fatty acid synthesis gene (fasn) in the liver was considerably reduced in the fish oil group compared to the normal diet group (p < 0.05). These results show that fish oil may reduce cholesterol accumulation and might be used as an effective tool for anti-atherosclerotic drug development and on functional foods with further research. • In this research article we have discussed the possible effect of fish oil over HCD fed Zebrafish. • We have observed a positive effect on fish oil fed Zebrafish. • We suggest that the fish oil may have ability to reduce cholesterol accumulation and blood cholesterol level reduction. • All fishes subjected to the study are male Zebrafish.