Function of SREBP1 in the Milk Fat Synthesis of Dairy Cow Mammary Epithelial Cells

Abstract

Sterol regulatory element-binding proteins (SREBPs) belong to a family of nuclear transcription factors. The question of which is the most important positive regulator in milk fat synthesis in dairy cow mammary epithelial cells (DCMECs) between SREBPs or other nuclear transcription factors, such as peroxisome proliferator-activated receptor γ (PPARγ), remains a controversial one. Recent studies have found that mTORC1 (the mammalian target of rapamycin C1) regulates SREBP1 to promote fat synthesis. Thus far, however, the interaction between the SREBP1 and mTOR (the mammalian target of rapamycin) pathways in the regulation of milk fat synthesis remains poorly understood. This study aimed to identify the function of SREBP1 in milk fat synthesis and to characterize the relationship between SREBP1 and mTOR in DCMECs. The effects of SREBP1 overexpression and gene silencing on milk fat synthesis and the effects of stearic acid and serum on SREBP1 expression in the upregulation of milk fat synthesis were investigated in DCMECs using immunostaining, Western blotting, real-time quantitative PCR, lipid droplet staining, and detection kits for triglyceride content. SREBP1 was found to be a positive regulator of milk fat synthesis and was shown to be regulated by stearic acid and serum. These findings indicate that SREBP1 is the key positive regulator in milk fat synthesis.

Biosynthesis of milk fat, protein, and lactose: roles of transcriptional and posttranscriptional regulation

“…Besides the inhibition by PUFA, saturated LCFA also can affect the activity of SREBP1. This was recently demonstrated in bovine mammary cells where stearic acid treatment increased the expression and the activity of SREBP1 resulting in increased TAG synthesis (125). The authors did not provide any mechanistic explanation for such effect.…”

“…Consequently, activation of PPAR could inhibit SREBP1 activity through Lipin 1 gene upregulation in the absence of mTOR activity. Data from a recent study on bovine mammary cells indicated a potential negative effect of SREBP1 on PPAR but also indicated a role for SREBP1 in controlling the expression of MTOR (125). In that study, overexpression of SREBF1 in bovine mammary epithelial cells increased expression of MTOR and synthesis of TAG but decreased the expression of the PPAR␥ gene (gene symbol PPARG).…”

“…To provide support for the lack of effect of PPAR␥ activation in preventing milk fat depression, the same experiment carried out in mouse (232) should be performed in cows or goats. It can also be argued that the role of PPAR␥ in controlling expression of milk fat synthesis-related genes in ruminants is SREBP1 dependent, as suggested by the positive effect of PPAR␥ activation on the expression of SREBF1 (125). Because PPAR␥ only works at a transcriptional level, the decrease in milk fat synthesis by t10,c12-CLA, which physically impedes the activation of SREBP1, might not be recapitulated by the activation of PPAR␥.…”

“…A more direct demonstration of a key role of SREBP1 in controlling the expression of milk fat-related genes was recently provided by a series of experiments by suppressing expression of SREBF1 in bovine mammary epithelial cells (i.e., siRNA technology) (134,165). In addition, overexpression of SREBF1 in cultured bovine and goat mammary epithelial cells increased the expression of several genes related to milk fat synthesis and increased secretion of triacylglycerol (TAG) (125).…”

β-Hydroxybutyrate Facilitates Fatty Acids Synthesis Mediated by Sterol Regulatory Element-Binding Protein1 in Bovine Mammary Epithelial Cells

“…Sterol regulatory element-binding protein 1 (SREBP1), a member of transcription factors consists of SREBP-1a and SREBP-1c, belongs to the basic helix-loop-helix-leucinezipper (bHLH-Zip) family [12,13]. Although SREBP-1a and SREBP-1c are encoded by one gene (SREBP1), they are different in sequence at both their 5' and 3' ends [12,13].…”