Metabolic insights from zebrafish genetics, physiology, and chemical biology

Metabolic diseases-atherosclerotic cardiovascular disease, type 2 diabetes mellitus, obesity, and non-alcoholic fatty liver disease--have reached pandemic proportions. Across gene, cell, organ, organism, and social-environmental scales, fundamental discoveries of the derangements that occur in these diseases are required to develop effective new treatments. Here we will review genetic, physiological, pathological and chemical biological discoveries in the emerging zebrafish model for studying metabolism and metabolic diseases. We present a synthesis of recent studies using forward and reverse genetic tools to make new contributions to our understanding of lipid trafficking, diabetes pathogenesis and complications, and to β-cell biology. The technical and physiological advantages and the pharmacological potential of this organism for discovery and validation of metabolic disease targets are stressed by our summary of recent findings. We conclude by arguing that metabolic research using zebrafish will benefit from adoption of conventional blood and tissue metabolite measurements, employment of modern imaging techniques, and development of more rigorous metabolic flux methods.