Zebrafish Lipid Metabolism: From Mediating Early Patterning to the Metabolism of Dietary Fat and Cholesterol

Abstract

Lipids serve essential functions in cells as signaling molecules, membrane components, and sources of energy. Defects in lipid metabolism are implicated in a number of pandemic human diseases, including diabetes, obesity, and hypercholesterolemia. approaches for disease prevention and treatment. Numerous studies have shown that the zebrafish is an excellent model for vertebrate lipid metabolism. In this chapter, we review studies that employ zebrafish to better understand lipid signaling and metabolism.

Disruption of ldlr causes increased LDL-c and vascular lipid accumulation in a zebrafish model of hypercholesterolemia

“…I) suggested the possibility of assessing other phenotypes beyond 5 dpf, when larvae begin to rely on exogenous sources of nutrients, including lipids, through feeding ( 20,50,51 ). Previous reports have indicated that treatment of 5 dpf larvae with a HCD resulted in elevated total cholesterol after 10 days of feeding, including evidence of increased LDL-c ( 35 ).…”

“…This would potentially correlate with increased transcription of ldlr , though additional transcripts would likely continue to be targeted by the MO in our model. The yolk plays a critical role in lipid metabolism in early development ( 8,50 ) and it is diffi cult to differentiate between changes that might affect the yolk, thereby affecting lipid traits in the embryo, compared with changes specifi c to experimental manipulation. It is important to note that, although we detected expression of ldlr at earlier stages when the yolk was still present, we did not assay cholesterol levels or induce dietary manipulations until after the stage at which the yolk was depleted and larvae began to feed.…”

“…Despite the large number of putative candidate genes identifi ed, the functions of many remain largely unknown, owing in part to the lack of physiologically relevant in vivo models with which to validate and characterize the functionality of associated variants ( 3, 4, 6-13 ). Development of novel models in which genes can be individually targeted will likely reveal functional roles for genetic determinants of blood lipid levels and may facilitate discovery of novel targets for drug development.The zebrafi sh is an excellent candidate for establishing genetic models of hyperlipidemia due to conservation of cell types and molecular pathways involved in lipid metabolism and cholesterol synthesis ( 8,(14)(15)(16)(17)(18)(19)(20). These include hepatocytes, adipocytes, and pancreatic acinar cells ( 17 ) as well as expression of genes involved in lipid transport and metabolism, such as LDL receptor ( ldlr ), sterol regulatory element binding protein ( srebp ) 1/2 , and HMG-CoA reductase ( Hmgcr ) ( 18-29 ).…”

“…The zebrafi sh is an excellent candidate for establishing genetic models of hyperlipidemia due to conservation of cell types and molecular pathways involved in lipid metabolism and cholesterol synthesis ( 8,(14)(15)(16)(17)(18)(19)(20). These include hepatocytes, adipocytes, and pancreatic acinar cells ( 17 ) as well as expression of genes involved in lipid transport and metabolism, such as LDL receptor ( ldlr ), sterol regulatory element binding protein ( srebp ) 1/2 , and HMG-CoA reductase ( Hmgcr ) ( 18-29 ).…”

Dietary Protein Source Influence on Body Size and Composition in Growing Zebrafish

“…Additionally, tank densities were different between the two studies, with the current study having three times the density of the previous work (e.g., current: *5.5 fish/L vs. *1.6 fish/L). 24 Although the zebrafish model has garnered much recent attention for its potential use in lipid and obesity research, [41][42][43][44][45][46][47] few studies have reported overall body composition outcomes. In the present work, the dietary protein source significantly impacted lean and fat mass outcomes.…”