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

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 (<i>MTTPL</i>), is differently expressed during peak egg production and induced by estrogen. We demonstrated that <i>MTTPL</i> facilitates hepatic lipid export. Overexpression of <i>MTTPL</i> 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 <i>MTTPL</i> knockdown impaired estrogen-induced lipid export. Mechanistically, <i>PPARα</i> directly activates the <i>MTTPL</i> promoter, and <i>miR-7439-3p</i> represses <i>MTTPL</i> via its 3'UTR; estrogen regulates <i>MTTPL</i> through <i>PPARα</i>-mediated transcriptional activation and post-transcriptional <i>miR-7439-3p</i> inhibition. This study identified <i>MTTPL</i> as a key hepatic lipid-transport mediator in laying hens, illuminating poultry-specific lipid metabolic regulation.