Metabolic insights from zebrafish genetics, physiology, and chemical biology

Abstract

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.

FOXN3 Regulates Hepatic Glucose Utilization

“…Beyond this narrow primary structure conservation, zebrafish models for studying glucose metabolism have emerged as a powerful approach to answering mechanistic questions relating to physiology and gene regulation (Schlegel and Gut, 2015) . Thus, we generated two transgenic zebrafish lines expressing the zebrafish foxn3 and human FOXN3 under the control of the constitutively active, liver-specific fabp10a promoter.…”

Signal transduction mechanism for glucagon-induced leptin gene expression in goldfish liver

“…The liver is one of the most abundant sites for leptin expression in goldfish 26, and it is also the metabolic center in fish 55. Glucagon is mainly produced in the gallbladder and intestine of goldfish 28, but its high expression signal could also be detected in the liver (Fig.…”

Integrative Physiology: At the Crossroads of Nutrition, Microbiota, Animal Physiology, and Human Health

“…Zebrafish physiology and metabolism display extensive conservation with humans and other mammals. This permits the zebrafish to effectively model key pathophysiological processes involved in human diseases such as inflammatory bowel disease, insulin resistance, diabetes, hepatic steatosis, dyslipidemia, atherosclerosis, and obesity (Hill et al, 2016; Marjoram and Bagnat, 2015; Renshaw and Trede, 2012; Schlegel and Gut, 2015). In addition to identification of novel disease genes and therapies, these models can be used to define the physiologic function of genes implicated by genome-wide association studies in humans (Minchin et al, 2015).…”