transcription factor PlagL2 regulates steps in chylomicron metabolism

Enterocytes assemble dietary lipids into chylomicron particles that are taken up by intestinal lacteal vessels and peripheral tissues. Although chylomicrons are known to assemble in part within membrane secretory pathways, the modifications required for efficient vascular uptake are unknown. We report that the transcription factor Pleomorphic adenoma gene-like 2 (PLAGL2) is essential for this aspect of dietary lipid metabolism. PlagL2-/- mice die from post-natal wasting owing to failure of fat absorption. Lipids modified in the absence of PlagL2 exit from enterocytes but fail to enter interstitial lacteal vessels. Dysregulation of enterocyte genes closely linked to intracellular membrane transport identified candidate regulators of critical steps in chylomicron assembly. PlagL2 thus regulates essential and poorly understood aspects of dietary lipid absorption and its deficiency represents an authentic animal model with implications for amelioration of obesity or the metabolic syndrome. Keywords: gene expression profiling analysis Total RNA was extracted from 4 knockout and 4 wild-type mouse small intestines at 18.5 dpc using the Macherey-Nagel Nucleospin kit. cRNA synthesis and labeling, hybridization to Affymetrix (Santa Clara, CA) MOE430 2.0 expression arrays, and data acquisition occurred on the Affymetrix GeneChip Instrument System.