COL6A1 Promotes Milk Production and Fat Synthesis Through the PI3K-Akt/Insulin/AMPK/PPAR Signaling Pathways in Dairy Cattle.

Exploring functional genes/sites and the molecular regulatory mechanisms underlying milk production traits in dairy cattle is crucial for improving the development of the dairy industry and human health. In our previous work, the gene collagen type VI alpha 1 (COL6A1) was found to be involved in milk fat metabolism from liver transcriptome data across various lactation periods of cows. Through the integration of Cattle QTLdb, FarmGTEx and qPCR data, the COL6A1 gene was found to be located within known quantitative trait loci (QTLs), adjacent to single-nucleotide polymorphisms (SNPs) associated with milk traits, and highly expressed in the mammary gland. After employing RNA interference technology, cell function and phenotype tests in bovine mammary epithelial cells revealed that the COL6A1 gene accelerated cell proliferation, cell cycle progression, and the synthesis of lipids and triglycerides by regulating the PI3K-Akt, insulin, AMPK, and PPAR signaling pathways. Notably, 22 SNPs within COL6A1 had potential breeding value because they were significantly associated with milk production traits, especially with milk fat. In summary, our findings demonstrate that the COL6A1 gene promotes milk production and fat synthesis via the PI3K-Akt/insulin/AMPK/PPAR signaling pathways, providing valuable genetic information for molecular breeding programs for dairy cattle.