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https://www.readbyqxmd.com/read/28202364/fatty-acid-synthase-modern-tumor-cell-biology-insights-into-a-classical-oncology-target
#1
REVIEW
Douglas Buckley, Gregory Duke, Timothy S Heuer, Marie O'Farrell, Allan Wagman, William McCulloch, George Kemble
Decades of preclinical and natural history studies have highlighted the potential of fatty acid synthase (FASN) as a bona fide drug target for oncology. This review will highlight the foundational concepts upon which this perspective is built. Published studies have shown high levels of FASN in patient tumor tissues are present at later stages of disease and this overexpression predicts poor prognosis. Preclinical studies have shown that experimental overexpression of FASN in previously normal cells leads to changes that are critical for establishing a tumor phenotype...
February 12, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28198625/curcumin-attenuates-n-nitrosodiethylamine-induced-liver-injury-in-mice-by-utilizing-the-method-of-metabonomics
#2
Peiyu Qiu, Jiachen Sun, Shuli Man, He Yang, Long Ma, Peng Yu, Wenyuan Gao
N-Nitrosodiethylamine (DEN) as one of food additives existed in cheddar cheese, processed meats, beer, water and so forth. It possessed a potent hepatocarcinogen in animals and humans. Curcumin as a natural dietary compound decreased DEN-induced hepatocarcinogenesis in this research. According to the histopathological examination macroof liver tissues, and biomarker detection in serum and livers, it demonstrated that curcumin attenuated DEN-induced hepatocarcinogenesis through parts of regulating the oxidant stress enzymes (T-SOD and CAT), liver function (ALT and AST) and LDHA, AFP level and COX-2/PGE2 pathway...
February 15, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28197637/inhibition-of-fasn-suppresses-migration-invasion-and-growth-in-hepatoma-carcinoma-cells-by-deregulating-the-hif-1%C3%AE-igfbp1-pathway
#3
Jiaojiao Gong, Shasha Shen, Yixuan Yang, Si Qin, Lifan Huang, Hongmin Zhang, Ling Chen, Yaqin Chen, Shiying Li, Sha She, Min Yang, Hong Ren, Huaidong Hu
Hepatocellular carcinoma is the second most common cause of cancer-related deaths worldwide. Due to a high propensity to metastasize, active angiogenesis and rapid proliferation, recurrence and poor prognosis are major obstacles for treatment and cure of this disease. However, the detailed mechanisms of how fatty acid synthase (FASN) promotes migration, invasion and healing in tumor cells remain unclear. In the present study, the previous results that FASN was expressed higher in cancer samples than in non-cancerous samples, and influenced migration, invasion of hepatoma carcinoma cells, were verified by immunohistochemistry, tissue microarrays, Transwell assay and wound healing assay...
March 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28190525/central-action-of-xenin-affects-the-expression-of-lipid-metabolism-related-genes-and-proteins-in-mouse-white-adipose-tissue
#4
Sharma Bhavya, Pei San Lew, Tooru M Mizuno
Xenin is a gastrointestinal hormone that reduces food intake when administered centrally and it has been hypothesized that central action of xenin participates in the regulation of whole-body metabolism. The present study was performed to address this hypothesis by investigating the central effect of xenin on the expression of genes and proteins that are involved in the regulation of lipid metabolism in white adipose tissue (WAT). Male obese ob/ob mice received intracerebroventricular (i.c.v.) injections of xenin (5μg) twice 12h apart...
February 9, 2017: Neuropeptides
https://www.readbyqxmd.com/read/28190475/calycosin-attenuates-triglyceride-accumulation-and-hepatic-fibrosis-in-murine-model-of-non-alcoholic-steatohepatitis-via-activating-farnesoid-x-receptor
#5
Xingping Duan, Qiang Meng, Changyuan Wang, Zhihao Liu, Qi Liu, Huijun Sun, Pengyuan Sun, Xiaobo Yang, Xiaokui Huo, Jinyong Peng, Kexin Liu
BACKGROUND: Non-alcoholic steatohepatitis (NASH) represents the more severe end of hepatic steatosis and is associated with progressive liver disease. Calycosin, derived from the root of Radix Astragali, has been demonstrated to have favorable efficacy on acute liver injury. PURPOSE: The present study was to investigate the hepatoprotective effect of calycosin on attenuating triglyceride accumulation and hepatic fibrosis, as well as explore the potential mechanism in murine model of NASH...
February 15, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/28183167/detection-of-superior-genotype-of-fatty-acid-synthase-fasn-in-korean-native-cattle-by-an-environment-adjusted-statistical-model
#6
Jeayoung Lee, Dongyep Oh, Hyunji Kim, Gabsue Jang, Seunguk Lee
Objective: This study examines the genetic factors influencing the phenotypes (four economic traits: oleic acid (C18:1), monounsaturated fatty acids (MUFAs), carcass weight (CWT), and marbling score (MS)) of Hanwoo. Methods: To enhance the accuracy of the genetic analysis, the study proposes a new statistical model that excludes environmental factors. A statistically adjusted, analysis of covariance (ANCOVA) model of environmental and genetic factors was developed, and estimated environmental effects (covariate effects of age and effects of calving farms) were excluded from the model...
February 1, 2017: Asian-Australasian Journal of Animal Sciences
https://www.readbyqxmd.com/read/28180141/identification-of-diagnostic-markers-involved-in-the-pathogenesis-of-gastric-cancer-through-itraq-based-quantitative-proteomics
#7
Zhen Jiang, Hongchun Shen, Bo Tang, Hui Chen, Qin Yu, Xingli Ji, Li Wang
We provide detailed datasets from our analysis of proteins that are differentially expressed in gastric cancer tissues compared with adjacent normal gastric tissues, as identified by iTRAQ-based quantitative proteomics. Also included is a set of representative images of immunohistochemical staining of gastric cancer tissues showing four levels of expression of fatty acid binding protein (FABP1) and fatty acid synthase (FASN). The data presented in this paper support the research article "Quantitative proteomic analysis reveals that proteins required for fatty acid metabolism may serve as diagnostic markers for gastric cancer" (Jiang et al...
April 2017: Data in Brief
https://www.readbyqxmd.com/read/28168742/astrocyte-lipid-metabolism-is-critical-for-synapse-development-and-function-in-vivo
#8
Anne-Lieke F van Deijk, Nutabi Camargo, Jaap Timmerman, Tim Heistek, Jos F Brouwers, Floriana Mogavero, Huibert D Mansvelder, August B Smit, Mark H G Verheijen
The brain is considered to be autonomous in lipid synthesis with astrocytes producing lipids far more efficiently than neurons. Accordingly, it is generally assumed that astrocyte-derived lipids are taken up by neurons to support synapse formation and function. Initial confirmation of this assumption has been obtained in cell cultures, but whether astrocyte-derived lipids support synapses in vivo is not known. Here, we address this issue and determined the role of astrocyte lipid metabolism in hippocampal synapse formation and function in vivo...
February 7, 2017: Glia
https://www.readbyqxmd.com/read/28159572/fasn-inhibition-and-taxane-treatment-combine-to-enhance-anti-tumor-efficacy-in-diverse-xenograft-tumor-models-through-disruption-of-tubulin-palmitoylation-and-microtubule-organization-and-fasn-inhibition-mediated-effects-on-oncogenic-signaling-and-gene-expression
#9
Timothy S Heuer, Richard Ventura, Kasia Mordec, Julie Lai, Marina Fridlib, Douglas Buckley, George Kemble
Palmitate, the enzymatic product of FASN, and palmitate-derived lipids support cell metabolism, membrane architecture, protein localization, and intracellular signaling. Tubulins are among many proteins that are modified post-translationally by acylation with palmitate. We show that FASN inhibition with TVB-3166 or TVB-3664 significantly reduces tubulin palmitoylation and mRNA expression. Disrupted microtubule organization in tumor cells is an additional consequence of FASN inhibition. FASN inhibition combined with taxane treatment enhances inhibition of in vitro tumor cell growth compared to treatment with either agent alone...
December 24, 2016: EBioMedicine
https://www.readbyqxmd.com/read/28145418/chronic-dietary-exposure-to-branched-chain-amino-acids-impairs-glucose-disposal-in-vegans-but-not-in-omnivores
#10
J Gojda, L Rossmeislová, R Straková, J Tůmová, M Elkalaf, M Jaček, P Tůma, J Potočková, E Krauzová, P Waldauf, J Trnka, V Štich, M Anděl
BACKGROUND/OBJECTIVES: Branched chain amino acids (BCAA) are among nutrients strongly linked with insulin sensitivity (IS) measures. We investigated the effects of a chronic increase of BCAA intake on IS in two groups of healthy subjects differing in their basal consumption of BCAA, that is, vegans and omnivores. SUBJECTS/METHODS: Eight vegans and eight matched omnivores (five men and three women in each group) received 15 g (women) or 20 g (men) of BCAA daily for 3 months...
February 1, 2017: European Journal of Clinical Nutrition
https://www.readbyqxmd.com/read/28143451/distinct-prostate-cancer-related-mrna-cargo-in-extracellular-vesicle-subsets-from-prostate-cell-lines
#11
Elisa Lázaro-Ibáñez, Taral R Lunavat, Su Chul Jang, Carmen Escobedo-Lucea, Jorge Oliver-De La Cruz, Pia Siljander, Jan Lötvall, Marjo Yliperttula
BACKGROUND: Multiple types of extracellular vesicles (EVs), including microvesicles (MVs) and exosomes (EXOs), are released by all cells constituting part of the cellular EV secretome. The bioactive cargo of EVs can be shuffled between cells and consists of lipids, metabolites, proteins, and nucleic acids, including multiple RNA species from non-coding RNAs to messenger RNAs (mRNAs). In this study, we hypothesized that the mRNA cargo of EVs could differ based on the EV cellular origin and subpopulation analyzed...
February 1, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28137779/cardiolipin-promotes-electron-transport-between-ubiquinone-and-complex-i-to-rescue-pink1-deficiency
#12
Melissa Vos, Ann Geens, Claudia Böhm, Liesbeth Deaulmerie, Jef Swerts, Matteo Rossi, Katleen Craessaerts, Elvira P Leites, Philip Seibler, Aleksandar Rakovic, Thora Lohnau, Bart De Strooper, Sarah-Maria Fendt, Vanessa A Morais, Christine Klein, Patrik Verstreken
PINK1 is mutated in Parkinson's disease (PD), and mutations cause mitochondrial defects that include inefficient electron transport between complex I and ubiquinone. Neurodegeneration is also connected to changes in lipid homeostasis, but how these are related to PINK1-induced mitochondrial dysfunction is unknown. Based on an unbiased genetic screen, we found that partial genetic and pharmacological inhibition of fatty acid synthase (FASN) suppresses toxicity induced by PINK1 deficiency in flies, mouse cells, patient-derived fibroblasts, and induced pluripotent stem cell-derived dopaminergic neurons...
January 30, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28131578/mrna-abundance-of-genes-involved-in-mammary-lipogenesis-during-fish-oil-or-trans-10-cis-12-cla-induced-milk-fat-depression-in-dairy-ewes
#13
P G Toral, G Hervás, A Belenguer, D Carreño, P Frutos
Milk fat depression (MFD) caused by trans-10,cis-12 18:2 is known to be mediated in cows and ewes by downregulation of mammary lipogenic genes. However, transcriptional mechanisms underlying marine lipid-induced MFD have not been well defined yet and the few available studies in ovine are not consistent. This trial was conducted to directly compare changes in animal performance, milk fatty acid composition, and particularly mammary mRNA abundance of candidate lipogenic genes and transcription factors in response to the inclusion of fish oil or trans-10,cis-12 18:2 in the dairy sheep diet...
January 25, 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28124996/expression-of-lipid-metabolism-related-proteins-differs-between-invasive-lobular-carcinoma-and-invasive-ductal-carcinoma
#14
Yoon Jin Cha, Hye Min Kim, Ja Seung Koo
We comparatively investigated the expression and clinical implications of lipid metabolism-related proteins in invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) of the breast. A total of 584 breast cancers (108 ILC and 476 IDC) were subjected to tissue microarray and immunohistochemical analysis for lipid metabolism-related proteins including hormone-sensitive lipase (HSL), perilipin A, fatty acid binding protein (FABP)4, carnitine palmitoyltransferase (CPT)-1, acyl-CoA oxidase 1, and fatty acid synthetase (FASN)...
January 23, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28119133/breast-cancer-metabolic-cross-talk-fibroblasts-are-hubs-and-breast-cancer-cells-are-gatherers-of-lipids
#15
Filipa Lopes-Coelho, Saudade André, Ana Félix, Jacinta Serpa
The cellular components of microenvironment are partners of cancer cells, sharing soluble factors and organic molecules to accomplish tumor energy and biomass demands. We tested the role of fibroblasts in fatty acids metabolism in breast cancer, addressing fatty acid synthase (FASN) expression and activity, the expression of lipids chaperons (FABPs) and transporters (FATPs) and lipids cellular content. We showed that the lipids increased in cancer cells exposed to fibroblasts conditioned media, showing that lipids transfer is crucial in this metabolic cross-talk...
January 21, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28118080/oncogene-dependent-requirement-of-fatty-acid-synthase-in-hepatocellular-carcinoma
#16
Li Che, Maria G Pilo, Antonio Cigliano, Gavinella Latte, Maria M Simile, Silvia Ribback, Frank Dombrowski, Matthias Evert, Xin Chen, Diego F Calvisi
Hepatocellular carcinoma (HCC), the most frequent primary tumor of the liver, is an aggressive cancer type with limited treatment options. Cumulating evidence underlines a crucial role of aberrant lipid biosynthesis (a process known as de novo lipogenesis) along carcinogenesis. Previous studies showed that suppression of fatty acid synthase (FASN), the major enzyme responsible for de novo lipogenesis, is highly detrimental for the in vitro growth of HCC cell lines. To assess whether de novo lipogenesis is required for liver carcinogenesis, we have generated various mouse models of liver cancer by stably overexpressing candidate oncogenes in the mouse liver via hydrodynamic gene delivery...
January 24, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28109099/-effect-of-hugan-qingzhi-tablets-on-ampk-pathway-activation-and-nf-%C3%AE%C2%BAb-p65-protein-expression-in-the-liver-of-rats-with-nonalcoholic-fatty-liver-disease
#17
Xiao-Rui Yao, Fan Xia, Wai-Jiao Tang, Ben-Jie Zhou
OBJECTIVE: To investigate the effect of Hugan Qingzhi tablets on lipid metabolism and inflammation in rats fed on high-fat diet and explore the underlying mechanisms. METHODS: Sixty male Sprague-Dawley rats were randomly divided into 6 groups, namely HFD group (with high-fat diet and distilled water), control group (with normal diet and distilled water), fenofibrate group (with high-fat diet and treatment with 0.1 g<kg fenofibrate suspension), and low-, moderate- and high-dose Hugan Qingzhi tablet groups (with high-fat diet and treatment with 0...
January 20, 2017: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
https://www.readbyqxmd.com/read/28107461/inhibition-of-fatty-acid-synthase-reduces-blastocyst-hatching-through-regulation-of-the-akt-pathway-in-pigs
#18
Jing Guo, Nam-Hyung Kim, Xiang-Shun Cui
Fatty acid synthase (FASN) is an enzyme responsible for the de novo synthesis of long-chain fatty acids. During oncogenesis, FASN plays a role in growth and survival rather than acting within the energy storage pathways. Here, the function of FASN during early embryonic development was studied using its specific inhibitor, C75. We found that the presence of the inhibitor reduced blastocyst hatching. FASN inhibition decreased Cpt1 expression, leading to a reduction in mitochondria numbers and ATP content. This inhibition of FASN resulted in the down-regulation of the AKT pathway, thereby triggering apoptosis through the activation of the p53 pathway...
2017: PloS One
https://www.readbyqxmd.com/read/28095627/melatonin-regulates-lipid-metabolism-in-porcine-oocytes
#19
Jun-Xue Jin, Sanghoon Lee, Anukul Taweechaipaisankul, Geon A Kim, Byeong Chun Lee
It is being increasingly recognized that the processes of lipogenesis and lipolysis are important for providing an essential energy source during oocyte maturation and embryo development. Recent studies demonstrated that melatonin has a role in lipid metabolism regulation, including lipogenesis, lipolysis and mitochondrial biogenesis. In this study, we attempted to investigate the effects of melatonin on lipid metabolism during porcine oocyte in vitro maturation. Melatonin treatment significantly enhanced the number of lipid droplets (LDs) and upregulated gene expression related to lipogenesis (ACACA, FASN, PPARγ, and SREBF1)...
January 17, 2017: Journal of Pineal Research
https://www.readbyqxmd.com/read/28088781/mir-30c-5p-ameliorates-hepatic-steatosis-in-leptin-receptor-deficient-db-db-mice-via-down-regulating-fasn
#20
Jiahui Fan, Huaping Li, Xiang Nie, Zhongwei Yin, Yanru Zhao, Chen Chen, Dao Wen Wang
Approximately 15-40% of the general adult population suffers from non-alcoholic fatty liver disease (NAFLD) worldwide. However, no drug is currently licensed for its treatment. In this study, we observed a significant reduction of miR-30c-5p in the liver of leptin receptor-deficient (db/db) mice. Remarkably, recombinant adeno-associated virus (rAAV)-mediated delivery of miR-30c-5p was sufficient to attenuate triglyceride accumulation and hepatic steatosis in db/db mice. Through computational prediction, KEGG analysis and Ago2 co-immunoprecipitation, we identified that miR-30c-5p directly targeted fatty acid synthase, a key enzyme in fatty acid biosynthesis...
January 9, 2017: Oncotarget
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