Chd7 regulates lipid metabolism and swim bladder inflation in zebrafish.

The chromodomain helicase remodeling enzyme, CHD7, has been directly linked to CHARGE syndrome, however recent studies show a wide variability of pathways regulated by the chromatin remodeling enzyme. Here, we show that chd7 mutant zebrafish present with a collection of dysregulated lipid metabolism enzymes in line with Pparγ regulated lipid metabolism. Consequently, we link lipid metabolism to swim bladder development and observe decreased size and non-inflated swim bladder during larval development. While loss-of-function of chd7 does not appear to affect the formation of the swim bladder during early stages and early pathways, it is required for expression of lipid metabolism enzymes, subsequently resulting in failure to inflate the swim bladder. Analysis of known underlying pathways indicate a functional role of fatty acid synthesis and lipid binding. Our investigations could show that significant depletion of fatty acid enzyme, elovl1, and the fatty acid binding protein, fabp7b, parallel to pparγ depletion, result in a dyslipidemia and subsequent failure to inflate the swim bladder. Our study is the first to investigate the multisystemic role of chd7 in correlation to swim bladder development and its fundamental underlying pathway in lipid metabolism, showing a necessity of chd7 for lipid homeostasis.