apoc2-mutant zebrafish to study hypertriglyceridemia

Hypertriglyceridemia is characterised by high levels of triglycerides in the blood and is associated with several metabolic disorders and with an increased risk of cardiovascular disease. It can be caused by several factors, including obesity, excessive alcohol consumption and an unhealthy diet. In addition, individuals with genetic defects in apolipoprotein-CII (APOC2; an activator of lipoprotein lipase, which hydrolyses triglycerides to deliver fatty acids to body tissues) display hypertriglyceridemia even on a normal diet. Here, Yury Miller and colleagues generated mutant zebrafish bearing apoc2 loss-of-function mutations. These animals, fed a normal diet, exhibit severe hypertriglyceridemia and accumulate lipid and lipid-laden macrophages in the vasculature, which constitute early events in the development of human atherosclerotic lesions. Notably, injection of wild-type zebrafish plasma with functional Apoc2 or a human APOC2-mimetic peptide can rescue hypertriglyceridemia in the mutants. This is the first animal model of APOC2 deficiency that can be used to understand mechanisms of human hypertriglyceridemia and to screen small molecules with therapeutic potential. Page 989