Epidermal growth factor stimulates fatty acid synthesis mainly via PLC-y1/Akt signaling pathway in dairy goat mammary epithelial cell

Authors: HUANG, JIANGTAO - Northwest A&f University; DAI, BANGGUO - Northwest A&f University; QU, HEXUAN - Northwest A&f University; ZHONG, YULING - Northwest A&f University; MA, YUE - Northwest A&f University; LUO, JUN - Northwest A&f University; HADSELL, DARRYL - Children'S Nutrition Research Center (CNRC); SHI, HUAIPING - Northwest A&f University

Submitted to: Animals
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/21/2020
Publication Date: 5/28/2020
Citation: Huang, J., Dai, B., Qu, H., Zhong, Y., Ma, Y., Luo, J., Hadsell, D., Shi, H. 2020. Epidermal growth factor stimulates fatty acid synthesis mainly via PLC-y1/Akt signaling pathway in dairy goat mammary epithelial cell. Animals. 10(6):930. https://doi.org/10.3390/ani10060930.
DOI: https://doi.org/10.3390/ani10060930

Interpretive Summary: Goat milk is the most widely consumed milk in the world and is considered to have many beneficial attributes both in terms of human health, environmental impact, and sustainability. One characteristic that contributes to the health benefits of goat milk is its fat composition. This study examines the regulation of fat synthesis by goat mammary cells. The work demonstrates that a protein growth factor known as epidermal growth factor can increase the ability of mammary cells to make fat through coordinated activation of genes known to contribute to the process. The study also identified two key signaling pathways that contribute to this increase. Application of knowledge learn from these results could lead to the development of novel strategies to influence fat composition in dairy goats.

Technical Abstract: Epidermal growth factor (EGF) acts as a ligand of the EGF receptor (EGFR) to activate the EGFR-mediated signaling pathways and is involved in the regulation of cell physiology. However, the roles of EGFR mediated signaling pathways in the regulation of lipid metabolism in goat mammary epithelial cells (GMECs) are poorly understood. To evaluate the impact of EGF on GMECs, the triglyceride (TG) content and lipid droplet were detected, using TG assay and immunofluorescence. Further, expression of lipogenic genes, the protein kinase B (Akt), phospholipase C-y1 (PLC-y1) and extracellular signal-regulated kinases (ERK)1/2 signaling pathways were measured by real-time polymerase chain reaction and Western blot, respectively. The results showed that the mRNA expression of EGFR gene was significantly upregulated in lactating goat mammary gland tissues compared to non-lactation period (p < 0.05). TG contents in EGF-treated GMECs were significantly increased (p < 0.05), and an increase of lipid droplets was also detected. In vitro studies demonstrated that the mRNA levels of lipogenesis-related FASN, ACC, SCD1, LXRa, LXRb and SP1 genes were positively correlated to the mRNA level of EGFR gene shown by gene overexpression and silencing (p < 0.05). The phosphorylations of Akt,ERK1/2 and PLC-y1 in GMECs were greatly upregulated in the presence of EGF, and specific inhibitors were capable of blocking the phosphorylation of Akt, ERK1/2 and PLC-y1. Compared with EGF-treated GMECs, the mRNA levels of FASN, ACC and SCD1 were significantly decreased in GMECs co-treated with PLC-y1 and Akt inhibitor and EGF (p < 0.05), and TG content was also dropped significantly. These observations implied that EGFR plays an important role in regulating de novo fatty acid synthesis in GMECs, mainly mediated by Akt and PLC-y1 signaling pathways.