scholarly journals Short communication: Effect of inhibition of fatty acid synthase on triglyceride accumulation and effect on lipid metabolism genes in goat mammary epithelial cells

2015 ◽  
Vol 98 (5) ◽  
pp. 3485-3491 ◽  
Author(s):  
J.J. Zhu ◽  
J. Luo ◽  
Y.T. Sun ◽  
H.B. Shi ◽  
J. Li ◽  
...  
2017 ◽  
Vol 57 (8) ◽  
pp. 1624 ◽  
Author(s):  
J. Luo ◽  
J. J. Zhu ◽  
Y. T. Sun ◽  
H. B. Shi ◽  
J. Li

Fatty acid synthase (FASN) is the key enzyme for de novo fatty acid synthesis from acetyl-CoA and malonyl-CoA. All the steps involved in fatty acid synthesis by FASN have been clearly defined in monogastrics and ruminants. However, there are no data on the mechanism of how FASN affects triglyceride synthesis. Inhibition of FASN in goat mammary epithelial cells by C75, a synthetic inhibitor of FASN activity, and shRNA markedly suppressed the accumulation of triglyceride in goat mammary epithelial cells. Meanwhile, C75 treatment significantly reduced the relative content of monounsaturated fatty acids (C16:1 and C18:1). Corresponding to the suppression of lipid accumulation, both of C75 and shRNA also decreased the mRNA expression of GPAM, AGPAT6 and DGAT2, all of which are related to triglyceride synthesis. The fact that treatment of malonyl-CoA decreased the expression of these genes is consistent with the results of shRNA treatment. Furthermore, the supplement of malonyl-CoA enhanced the suppression on GPAM, AGPAT6, LPIN1, DGAT1 and DGAT2. The results underscore the role of malonyl-CoA in inhibition of FASN in regulating triglyceride synthesis in goat mammary epithelial cells.


PPAR Research ◽  
2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Hengbo Shi ◽  
Wangsheng Zhao ◽  
Changhui Zhang ◽  
Khuram Shahzad ◽  
Jun Luo ◽  
...  

To explore the large-scale effect of peroxisome proliferator-activated receptorγ(PPARG) in goat mammary epithelial cells (GMEC), an oligonucleotide microarray platform was used for transcriptome profiling in cells overexpressingPPARGand incubated with or without rosiglitazone (ROSI, a PPARγagonist). A total of 1143 differentially expressed genes (DEG) due to treatment were detected. The Dynamic Impact Approach (DIA) analysis uncovered the most impacted and induced pathways “fatty acid elongation in mitochondria,” “glycosaminoglycan biosynthesis-keratan sulfate,” and “pentose phosphate pathway.” The data highlights the central role ofPPARGin milk fatty acid metabolism via controlling fatty acid elongation, biosynthesis of unsaturated fatty acid, lipid formation, and lipid secretion; furthermore, its role related to carbohydrate metabolism promotes the production of intermediates required for milk fat synthesis. Analysis of upstream regulators indicated thatPPARGparticipates in multiple physiological processes via controlling or cross talking with other key transcription factors such asPPARDandNR1H3(also known as liver-X-receptor-α). This transcriptome-wide analysis represents the first attempt to better understand the biological relevance of PPARG expression in ruminant mammary cells. Overall, the data underscored the importance of PPARG in mammary lipid metabolism and transcription factor control.


2017 ◽  
Vol 2017 ◽  
pp. 1-12
Author(s):  
Gaoxiao Xu ◽  
Saixing Duan ◽  
Jianye Hou ◽  
Zhongxin Wei ◽  
Guangwei Zhao

It has been demonstrated that the activator protein related transcription factor Finkel-Biskis-Jinkins murine osteosarcoma B (GosB) is involved in preadipocyte differentiation and triacylglycerol synthesis. However, the role of GosB in regulating the synthesis of milk fatty acid in mouse mammary glands remains unclear. This research uncovered potentially new roles of GosB in suppressing milk fatty acid synthesis. Results revealed that GosB had the highest expression in lung tissue and showed a higher expression level during nonlactation than during lactation. GosB inhibited the expression of fatty acid synthase (FASN), stearoyl-CoA desaturase (SCD), fatty acid binding protein 4 (FABP4), diacylglycerol acyltransferase 1 (DGAT1), perilipin 2 (PLIN2), perilipin 3 (PLIN3), and C/EBPα in mouse mammary gland epithelial cells (MEC). In addition, GosB reduced cellular triglyceride content and the accumulation of lipid droplets; in particular, GosB enhanced saturated fatty acid concentration (C16:0 and C18:0). The PPARγ agonist, rosiglitazone (ROSI), promoted apoptosis and inhibited cell proliferation. GosB increased the expression of Bcl-2 and protected MEC from ROSI-induced apoptosis. Furthermore, MECs were protected from apoptosis through the GosB regulation of intracellular calcium concentrations. These findings suggest that GosB may regulate mammary epithelial cells milk fat synthesis and apoptosis via PPARγ in mouse mammary glands.


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