Studying non-alcoholic fatty liver disease with zebrafish: a confluence of optics, genetics, and physiology

Obesity is a public health crisis. New methods for amelioration of its consequences are required because it is very unlikely that the social and economic factors driving it will be reversed. The pathological accumulation of neutral lipids in the liver (hepatic steatosis) is an obesity-related problem whose molecular underpinnings are unknown and whose effective treatment is lacking. Here I review how zebrafish, a powerful model organism long-used for studying vertebrate developmental programs, is being harnessed to uncover new factors that contribute to normal liver lipid handling. Attention is given to dietary models and individual mutants. I speculate on the possible roles of non-hepatocyte residents of the liver, the adipose tissue, and gut microbiome on the development of hepatic steatosis. The highlighted work and future directions may lead to fresh insights into the pathogenesis and treatment of excess liver lipid states.