Fatty acid elongase7 is regulated via SP1 and is involved in lipid accumulation in bovine mammary epithelial cells

Abstract

Fatty Acid Elongase 7 (ELOVL7) is the newly discovered protein on human that catalyzes the rate-limiting step towards the synthesis of very long-chain fatty acids and exhibits the highest activity toward C18: 3 (n-3) acyl-CoAs, which is the precursor of eicosapentaenoic acid (EPA, 20: 5n-3). However, in ruminants, an overall understanding of ELOVLs gene family and the transcriptional regulation of ELOVL7 remain unknown. The purpose of this study is to investigate the transcriptional regulation and the influence of bovine ELOVL7 in bovine mammary epithelial cells (bMECs). Quantitative real-time PCR analysis demonstrated that ELOVLs gene family had differential expression patterns in bMECs, and bovine ELOVL7 was expressed in a tissue-specific manner, which was high in kidney, followed by in abdominal fat and in bMECs. Promoter analysis of bovine ELOVL7, including bioinformatics analyzes, dual-luciferase reporter assays, protein pull-down assay, Western blot assay, over-expression and RNA interference assay, have independently and synthetically demonstrated that transcription factor Sp1 (SP1) specifically interacted with the GC-box at -143 to -128 base pair on ELOVL7 promoter. Furthermore, the exogenous α-linolenic acid (ALA, 18: 3n-3), strengthened the binding of SP1 to the ELOVL7 proximal promoter, resulting in the accumulation of lipid droplets in bMECs. In conclusion, these data suggest that the transcription of bovine ELOVL7 is affected by the binding of SP1 and the treatment of ALA, moreover, enlightening us the profound role of SP1 in modulating lipid synthesis of the mammary gland in cattle.

Quantitative proteomics analysis of young and elderly skin with DIA mass spectrometry reveals new skin aging-related proteins

“…Therefore, we speculate that these two proteins may be associated with reduced sebum secretion in the elderly, leading to a dry and desquamating phenotype. Other upregulated DEPs included fatty acid elongase 7 (ELOVL7), which participates in the synthesis and extension of very long-chain fatty acids [ 28 ], and arachidonate 15-lipoxygenase B (ALOX15B), a key enzyme in the metabolism of polyunsaturated fatty acids. The latter finding deserves further scrutiny, since downregulation of ALOX15B gene expression in light-damaged skin has been reported previously [ 29 ].…”

Characteristics of the fads2 gene promoter in marine teleost Epinephelus coioides and role of Sp1-binding site in determining promoter activity

“…labrax fads 2 gene promoters without an Sp1 site showed lower activity, and thus it is speculated that the low expression of fads 2 can be attributed to their incomplete and less active promoter 11 , 17 . Recently, the Sp1 binding site was detected in mammalian FADS and ELOVL7 promoters, and Sp1 up-regulated the expression of Fads2 and Elovl7 40 , 41 . These results suggested that the lack of Sp1 binding site maybe a reason leading to the low promoter activity of fads 2, and thus result in low hepatic fads 2 expression in carnivorous marine teleost, like E .…”

Effect of diets supplemented with starch and corn oil, marine algae, or hydrogenated palm oil on mammary lipogenic gene expression in cows and goats: A comparative study

“…Among those in goats, 2 positive correlations were observed between SCD5 and the milk desaturation ratios of cis-9 14:1/14:0 and cis-9,trans-11 18:2/trans-11 18:1, and 3 positive correlations were observed between LPL and cis-9,trans-11 CLA, trans-8,cis-10 CLA, and 20:3n-6; however, these associations require further investigation. Notably, specifically in cows, the transcription factor SP1 was correlated with the yield (g/d) of 14 individual FA (6:0, 8:0, cis-9 10: 1, iso-13:0, iso-14:0, iso-15:0, iso-16:0, 14:0, trans-9 14:1, anteiso-15:0, anteiso-17:0, cis-7 16:1, 18:3n-3, 24:0) or FA sum (C4-C14, <C16) or desaturation ratios, which require further investigation because of the role of this transcription factor in a wide range of cellular processes in mammalian cells (Chen et al, 2018).…”