Evidence for the existence of de novo lipogenesis in goose granulosa cells
Rui WenXiang GanShenqiang HuShanyan GaoYan DengJiamin QiuWenqiang SunLiang LiChunchun HanJiwei HuJiwen Wang
26
Citation
53
Reference
10
Related Paper
Citation Trend
Abstract:
De novo lipogenesis (DNL) is an important physiological mechanism, but it is poorly understood in avian follicles. The protein distribution patterns of three key genes related to DNL (i.e., FAS, ACC, and PPARγ) were firstly determined in geese developing follicles using immunohistochemistry, and our results showed that all three proteins were present in both prehierarchical and hierarchical follicles. Furthermore, it was revealed by qPCR that transcripts of these three genes were widely expressed in theca and granulosa layers of all staged follicles; however, the expression of DNL-related genes in granulosa cell changed significantly (P < 0.05) after follicle selection (FAS and PPARγ) and before ovulation (FAS). It is suggested that the DNL mechanism may be closely related to the follicular selection, while FAS may be closely associated with ovulation and steroidogenesis. These results suggested that DNL exists throughout follicle development and it potentially have an important role in the process of follicular selection, development, steroidogenesis, and ovulation, especially in their granulosa layers. To further demonstrate this point, granulosa cells isolated from hierarchical follicles were cultured in vitro. By analyzing the mRNA and protein expression patterns of these three genes, the fatty acid synthase enzyme activity, the contents of extracellular triglyceride, and intracellular lipids, as well as the cell activity at different time points of in vitro culture (0, 6, 12, and 18 h). These findings not only ensured the existence of DNL in the granulosa cells of goose follicles, but also suggested the complex process of lipid metabolism that associated with DNL, may play an important role in cell proliferation and physiological functions. Taken together, we first confirmed the existence of lipid metabolism, especially the DNL in goose follicles, and further suggested its role in the follicles, especially in the granulosa cells.Keywords:
Lipogenesis
Granulosa cell
Objective To explore the value of ultrasound B in observing follicle growth and developement ovulation and treatment of sterility.Methods Use ultrasound B to observe ova developement of 70 patient's 72 natural period and 50 drug ovulation period.Results The average daily growth of natural period follicle is 1.90mm,the follicle average diameter before ovulation is 21.30mm. The average growth of drug-promoted ovulation follicle is 2 42mm,the average diameter of follicle before ovulation is 23 85mm. The follicle grow at different speed before ovulation.Conclusion Through the serial observation of follicle's growth、 developement、ovulation by ultrasund B,we can find out the reasons of sterility,guide clinical treatment, increase the pregnancy rate of the patients.
Cite
Citations (0)
Abstract Metabolic diseases such as obesity, type 2 diabetes mellitus and non-alcoholic steatohepatitis (NASH) are closely linked to aberrant synthesis of endogenous fatty acids in the liver, called de novo lipogenesis, which is mediated by the enzyme fatty acid synthase (FASN). Endogenously synthesized fatty acids are either saturated or monounsaturated and can adversely affect metabolic health through mechanisms that are not sufficiently understood. Here we show that lipogenesis critically determines the use of food-derived, metabolically beneficial polyunsaturated fatty acids (PUFA). We found a patient with a hypofunctional heterozygous de novo Arg2177Cys mutation in FASN, which resulted in a cysteine-dependent, non-enzymatic acetylation of FASN and decreased protein stability. Remarkably, the patient showed markedly elevated levels of polyunsaturated fatty acids, whereas patients with high FASN expression in the liver showed diminished levels. Moreover, pharmacological intervention with the FASN-inhibitor TVB-2640 in patients with NASH was sufficient to increase the rate of PUFA use in circulating lipids. In line, the incorporation rate of supplemented omega-3 PUFA in obesogenic diet could be dramatically increased by reducing the lipogenesis rate in mice. Mechanistically, we show that fatty acid storage preferences are determined by an active, enzymatic process dependent on FASN and DGAT2. Our results demonstrate that low lipogenesis rates increase the efficiency of PUFA incorporation into complex lipids, whereas high lipogenesis rates lead to low PUFA use. This has critical clinical implications for the prediction of low therapeutic success of omega-3 supplementation in patients with high lipogenesis and provides evidence for the urgent development of combined therapy options targeting lipogenesis and PUFA supplementation.
Lipogenesis
Fatty acid synthesis
Steatohepatitis
Cite
Citations (0)
Background: Cumulating evidence underlines the crucial role of aberrant lipid biosyntesis in human hepatocellular carcinoma (HCC). Here, we investigated the oncogenic potential of fatty acid synthase (FASN), the master regulator of de novo lipogenesis, in the mouse liver.
Lipogenesis
Fatty acid synthesis
Cite
Citations (2)
The fatty acid synthase(FASN) plays a central role in lipogenesis of mammals through the synthesis of saturated long-chain fatty acids from acetyl-CoA and malonyl-CoA.The fatty acid synthase is a key enzyme of lipogenesis and may play a crucial role in the weight variability of the abdominal adipose tissue.In this review the status,function,mapping,structure of FASN gene,and the association between genetic variation of FASN gene and production trait were summarized.
Lipogenesis
Fatty acid synthesis
Cite
Citations (1)
De novo lipogenesis (DNL) is a complex yet highly regulated metabolic pathway, and transcription factors such as liver X receptor (LXR), sterol regulatory element-binding protein-1c (SREBP-1c), and carbohydrate response element binding protein (ChREBP) exert significant control over the de novo synthesis of fatty acids. An increase in de novo lipogenesis (DNL) is an important contributor to increased fat mass, while a reduction in lipogenesis may be protective against the development of obesity. In this review, we explore fatty acid synthesis in the context of new insights gleaned from global and tissue-specific gene knockout mouse models of enzymes involved in fatty acid synthesis, namely acetyl-CoA carboxylase, fatty acid synthase, fatty acid elongase 6, and stearoyl-CoA desaturase 1. A disruption in fatty acid synthesis, induced by the deficiency of any one of these enzymes, affects lipid metabolism and in some cases may protect against obesity in a tissue and gene-specific manner, as discussed in detail in this review.
Lipogenesis
Fatty acid synthesis
Acetyl-CoA Carboxylase
De novo synthesis
Carbohydrate-responsive element-binding protein
Cite
Citations (388)
Lipogenesis
Fatty acid synthesis
Cite
Citations (41)
Lipogenesis
Retinoblastoma
Fatty acid synthesis
Cite
Citations (0)
Abstract Aberrant metabolism, including increased de novo lipogenesis, is one of the hallmarks of cancer. Fatty Acid Synthase (Fasn) catalyzes the de novo synthesis of long-chain fatty acids from acetyl-CoA and malonyl-CoA. Increased Fasn expression has been reported in multiple tumor types, and inhibition of Fasn expression has been shown to have tumor-suppressing activity. However, how increased de novo lipogenesis contributes to tumor initiation and progression, especially in vivo, remains unknown. In our previous studies, we showed that overexpression of the activated form of AKT (myr-AKT) induced de novo lipogenesis, hepatocyte proliferation and, eventually, liver cancer formation in mice. The tumorigenesis process could be significantly accelerated via co-expression of activated form of Ras. In the AKTRas tumor model, tumors were predominantly (>80%) hepatocellular carcinoma (HCC), and the remaining (<20%) were intrahepatic cholangiocarcinoma (ICC). The ICCs were induced via hepatocyte-biliary epithelial cell metaplasia in a Notch dependent manner. Intriguingly, fat droplet formation, increased expression of Fasn and other lipogenesis pathway genes were identified in HCC lesions, but not ICC lesions. To define whether Fasn-mediated de novo lipogenesis is a key metabolic event downstream of mTORC1 during AKTRas-induced hepatocarcinogenesis, we utilized Fasn flox/flox mice, and co-expressed AKTRas in the Fasn KO hepatocytes. Of note, we found that ablation of Fasn completely inhibited AKT induced lipogenesis and hepatocyte proliferation in mice. However, loss of Fasn modestly delayed AKTRas-induced liver tumor development. Histological analysis revealed that these tumor lesions were predominantly ICCs. The ICC cells were highly proliferative, and did not express Fasn or any other lipogenic pathway gene. The results suggest that Fasn-mediated de novo lipogenesis is required for AKTRas-induced HCC formation, but this process is dispensable for ICC formation. In summary, our experiments support a critical role for Fasn as a downstream effector of mTORC1 in HCC pathogenesis. However, Fasn-mediated do novo fatty acid synthesis is not required in all tumor types. It is likely that other sources of fatty acids, presumably including those derived from the diet, can be utilized by cancer cells for membrane synthesis during cell proliferation. Citation Format: Xin Chen, Lei Li, Chunmei Wang, Matthias Evert, Diego F. Calvisi, Clay F. Semenkovich. Role of fatty acid synthase and do novo lipogenesis in liver cancer development in mice. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1880. doi:10.1158/1538-7445.AM2013-1880 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
Lipogenesis
Fatty acid synthesis
Cite
Citations (0)
Lipogenesis
Fatty acid synthesis
Cite
Citations (1)