Identification of Milk Fat Metabolism-Related Pathways of the Bovine Mammary Gland during Mid and Late Lactation and Functional Verification of the ACSL4 Gene

Abstract

The concentration of bovine milk fat changes regularly with lactation stages. In particular, milk fat percentage is higher in late lactation than mid lactation. Furthermore, milk fat composition is highly subject to a few genes. Thus, transcriptome sequencing was performed to explore the expression patterns of differentially-expressed genes (DEGs) in the parenchymal mammary gland of Holstein dairy cows between mid and late lactation. The 725 DEGs were screened (fold change > 2 and p-value < 0.05), and the peroxisome proliferator-activated receptor (PPAR) signaling pathway associated with lipid synthesis had a significant variation between the two periods (p-value < 0.05). The activation of the PPAR signal pathway may a key factor in the increasing of milk fat content in late lactation compared to mid lactation. Acyl-CoA synthetase long-chain family member 4 (ACSL4), a member of the PPAR signaling pathway, was upregulated in late lactation compared to mid lactation (p < 0.05). ACSL4 catalyzes the activation of long-chain fatty acids for cellular lipid synthesis. However, it remains uncertain that the molecular mechanism of milk fat synthesis is regulated by ACSL4 in dairy cows. Subsequently, the function verification of ACSL4 was performed in bovine mammary epithelial cells (BMECs). The upregulated expression of ACSL4 was accompanied by the increase of the concentration of intracellular triglycerides, whereas knockdown of ACSL4 decreased the concentration of intracellular triglycerides, which demonstrated that ACSL4 plays an important role in modulating milk fat synthesis. In conclusion, the results displayed that ACSL4 expression regulates triglyceride metabolism in ruminant mammary cells.

ACSL4 Directs Intramuscular Adipogenesis and Fatty Acid Composition in Pigs

“…It suggests that the ACSL4 could stimulate adipogenesis and is more effective in the early stage of adipogenic differentiation. Therefore, consistent with other studies, ACSL4 is a positive regulator of adipogenic differentiation of adipocytes [ 9 , 25 , 26 ], epithelial cells [ 27 ], and smooth muscle cells [ 28 ] from different tissue origins. Our data also showed that ACSL4 expression remains low in the matured adipocytes, indicating that ACSL4 is dispensable for the maintenance of fat cells and lipid storage.…”

The Overlooked Transformation Mechanisms of VLCFAs: Peroxisomal β-Oxidation

“…PPARγ expression increases during changes in the lactation period [55,56], thereby regulating peroxisomal β-oxidation to prevent metabolic stress. Research further confirmed the importance of PPARγ in regulating milk fat production [57,58]. Similarly, as milk-producing ruminants, goats and sheep are also regulated by PPARγ.…”

Fatty Acid Metabolism-Related lncRNAs Are Potential Biomarkers for Predicting the Overall Survival of Patients With Colorectal Cancer

“…Present studies have demonstrated that the ACSL4 dysregulation is associated with the progression of many malignant tumors, including gastric cancer, prostate cancer, and colorectal cancer ( 57 – 59 ). What’s more, ACSL4 could regulate lipogenesis by affecting the expression of FASN and ACC1 ( 60 , 61 ). Therefore, we speculated that lncRNATSPEAR-AS2 could affect fatty acid metabolism of CRC through the targeted regulation of ACSL4, which still needs further experiments to prove.…”