A Dual-Regulatory Mechanism of Estrogen on MTTPL-Mediated Hepatic Lipid Transport in Chickens: Involvement of PPARα and miR-7439-3p

High Resolution Image Download MS PowerPoint Slide The liver of laying hens is the primary site for lipid synthesis and very-low-density lipoprotein (VLDL) assembly, essential for yolk formation. Unlike mammals, chickens do not require the canonical microsomal triglyceride transfer protein (MTTP) for the VLDL assembly. A newly identified gene, microsomal triglyceride transfer protein-like ( MTTPL ), is differently expressed during peak egg production and induced by estrogen. We demonstrated that MTTPL facilitates hepatic lipid export. Overexpression of MTTPL significantly reduced intracellular triglycerides (TG), total cholesterol (TC), and VLDL levels while increasing their extracellular concentrations, accompanied by upregulated expression of lipid-transport genes. In vivo, hepatic MTTPL knockdown impaired estrogen-induced lipid export. Mechanistically, PPARα directly activates the MTTPL promoter, and miR-7439-3p represses MTTPL via its 3′UTR; estrogen regulates MTTPL through PPARα -mediated transcriptional activation and post-transcriptional miR-7439-3p inhibition. This study identified MTTPL as a key hepatic lipid-transport mediator in laying hens, illuminating poultry-specific lipid metabolic regulation.