We report the transcriptional response of the zebrafish digestive organs to an acute high-fat feed using RNASeq analysis and highlight the changes in gene expression involved in the synthesis, storage, and dispersal of lipids. These key physiological responses to a high-fat meal all stem from the endoplasmic reticulum (ER), where lipids are formed and assigned to their fates. Overall design: A feeding time course was undertaken with 6.5-dpf larval zebrafish. Triplicate samples were independently prepared from pairwise crosses fed either high-fat or low-fat food. 5% egg yolk emulsion (high-fat) feeds and 10% egg white (low-fat) feeds were prepared. At the appropriate time points, digestive organs (intestine, liver, pancreas) were dissected from 10 anesthetized larval zebrafish. Unfed controls were used to determine a transcriptional baseline.