Thyroid hormone responsive protein spot 14 enhances lipogenesis in bovine mammary epithelial cells

Abstract

Thyroid hormone responsive spot 14 (THRSP, Spot14, S14) is a nuclear protein that regulates milk fat synthesis. To investigate the role of THRSP in lipogenesis in the dairy cow mammary gland, first, we examined the association between milk fat concentration and THRSP expression in the mammary gland. We found that the dairy cow mammary glands that produced milk with high fat had high THRSP mRNA and protein levels. Additionally, the study described the consequences of overexpression or depletion of THRSP on lipogenesis in cultured bovine mammary epithelial cells (BMECs). We found that BMECs with overexpressed THRSP increased triacylglycerol levels and enhanced the expression of FAS, PPARγ, and SREBP1, compared with the control BMECs. Depletion of THRSP produced the opposite effects. Overall, increased mammary expression of THRSP can be a marker of high fat. In addition, our results provide evidence that THRSP may regulate expression of PPARγ and SREBP1 and can regulate milk fat synthesis by directly affecting the activity of some classical lipogenic enzymes.

Sebaceous Gland Atrophy in Psoriasis: An Explanation for Psoriatic Alopecia?

“…Expression of S14 is controlled by nutritional and hormonal factors and is restricted to liver and adipose tissue, particularly in lipomatous nodules. Suggestive of a role in lipid metabolism, it is also expressed in lipogenic breast cancers (Moncur et al, 1998) and upregulates lipogenesis in bovine mammary epithelial cells (Cui et al, 2015)…”

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

“…Very recently it was demonstrated in bovine mammary epithelial cells that the overexpression of Spot14 increases TAG synthesis and the expression of FASN, SREBF1, and PPARG (57). Opposite results were obtained from the inhibition of Spot14 expression (57). It remains to be determined whether Spot14 is able to bind directly to the promoter region of any milk-fat related genes, including SREBF1 and PPARG, and if it can bind and be directly activated or inhibited by nutrients, including LCFA.…”

“…In Spot14-null and Spot14-overexpressing mice, it was observed that only a decrease of milk fat synthesis in the former and an increase in the proportion of medium-chain FA in milk TAG in the latter (but no change in total milk fat) occurred. In addition, the main finding was that there was increased activity of fatty acid synthase without any effect on expression of proteins involved in milk fat synthesis (57).…”

Effects of Dietary Vegetable Oils on Mammary Lipid-Related Genes in Holstein Dairy Cows

“…Thyroid hormone-inducible hepatic protein (THRSP) was upregulated on days 21 and 42 with OO (Table 4), whereas this protein was upregulated on day 42 and downregulated on day 63 with HVO ( Table 5). Cui et al [29] reported that dairy cow mammary glands producing milk with high fat content could have high THRSP mRNA and protein levels. They also observed that mammary epithelial cells with overexpressed THRSP can increase TAG levels and enhanced abundance of FASN, PPARG, and SREBP1, resulting in a critical role in de novo lipogenesis and consequently influencing milk fat synthesis.…”