Project description:The fatty acid synthase (FASN) is the major fat synthesizing enzyme. FASN is an indispensable enzyme because mice with genetic deletion of Fasn are not viable. Apart from its physiological function, previous studies indicated that FASN could also exert a pathophysiological role, in the heart, because patients with heart failure showed up-reguation of FASN. To investigate the in vivo function of FASN up-regulation in the heart, we generated mice with myocardium-specific expression of FASN under control of the alpha-MHC promoter. Two different founder lines were generated with high and low FASN over-expression. Microarray gene expression profiling of heart tissue was performed of heart tissue from transgenic mice with high and low FASN expression Microarray gene expression profiling was performed with heart tissue isolated from three study groups: (i) Transgenic mice with high cardiac FASN expression, (ii) transgenic mice with low cardiac FASN expression, and (iii) B6 control mice.
Project description:The fatty acid synthase (FASN) is the major fat synthesizing enzyme. FASN is an indispensable enzyme because mice with genetic deletion of Fasn are not viable. Apart from its physiological function, previous studies indicated that FASN could also exert a pathophysiological role, in the heart, because patients with heart failure showed up-reguation of FASN. To investigate the in vivo function of FASN up-regulation in the heart, we generated mice with myocardium-specific expression of FASN under control of the alpha-MHC promoter. Two different founder lines were generated with high and low FASN over-expression. Microarray gene expression profiling of heart tissue was performed of heart tissue from transgenic mice with high and low FASN expression
Project description:Fatty acid synthase is a major enzyme involved in de novo lipogenesis, associated with energy homeostasis, lipid storage and signalling in normal liver cells. The effect of fatty acid synthase knockdown in normal liver cells (THLE 2) using siRNA mediated gene silencing were assesed for global gene deregulations. The deregulated metabolism, cell signalling and cell cycle pathway related gene expressions were analysed. Statistical significance values were also recorded. This expermental analysis clearly points to a important biochemical role for FASN in normal liver cell physiology. Total RNA was extracted from the THLE 2 cells transfected with FASN siRNA at 48h, along with its untransfected control cells. cDNA converted samples were run on microarray platform- Illumina HumanHT-12 V4.0 expression beadchip
Project description:Cigarette smoke has been demonstrated to stimulate the growth of existing bladder tumors by enhancing the survival and proliferation of cancer cells through the action of carcinogens present in smoke. Concurrently, Fatty Acid Synthase (FASN), a key enzyme in fatty acid synthesis crucial for lipid metabolism, exhibits dysregulation in various cancer types, often correlating with aggressive phenotypes. In this study, we reveal altered fatty acid metabolism and elevated FASN and fatty acid levels, specifically in current smokers with bladder cancer (BLCA). Notably, increased FASN levels under smoke exposure are attributed to epigenetic alterations affecting fatty acid metabolism. Cells exposed to cigarette smoke demonstrate a metabolic shift in utilizing glutamine as a carbon source and producing fatty acids. The genetic and pharmacological inhibition of FASN effectively reduces tumor growth in a CAM model exposed to smoke. FASN inhibitors like TVB 2640, currently in phase II clinical trialsclinical trials in various cancer types, may be effective for smokers with BLCA exhibiting high FASN levels. In general, FASN inhibition offers therapeutic promise for mitigating the impact of cigarette smoke on bladder cancer progression.
Project description:ATF6 is a key regulator of the unfolded protein response. Through use of zebrafish and cultured cells we demonstrate that ATF6 drives fatty liver disease by interaction with fatty acid synthase (FASN).
Project description:Myelination calls for a tremendous surge in cell metabolism towards lipids and membrane production. However, functional relevance of de novo fatty acid synthesis in myelinating cells remains unclear. We generated mutant mice in which the enzyme fatty acid synthase (FASN) was depleted conditionally in Schwann cells, the myelinating glial cells of the peripheral nervous system. To address how lack of FASN was affecting the development of the peripheral nervous system, we screened with an Affymetrix Transcriptomic approach the transcriptome of sciatic nerves and roots of P60 FASN mutant mice, comparing to control mice.
Project description:Alterations in gene expression following fatty acid synthase inhibtion were evaluated in androgen sensitive LNCaP cells and castration resistant 22Rv1 and LNCaP-95 cells. Cell were exposed to 2 concentrations (0.1 and 0.5 uM) of FASN inhibitor IPI-9119 or DMSO for 6 days.
Project description:Mammalian fatty acid synthase (FASN) is a lipogenic enzyme that catalyzes the formation of the long chain saturated fatty acid palmitate from acetyl and malonyl CoA in the presence of NADPH. Mammalian cells acquire fatty acids through dietary sources or through FASN. Although most mammalian cells express FASN at low levels, it is upregulated in cancers and during replication of many viruses. The precise role of FASN in disease pathogenesis is poorly understood, and whether de novo fatty acid synthesis contributes to host or viral protein acylation has been traditionally difficult to study. We describe a cell permeable, click-chemistry compatible alkynyl-acetate analog (5-Hexynoic acid, or "Alk-4") that functions as a reporter of FASN-dependent protein acylation. Alk-4 metabolic labeling enabled biotin-based purification and identification of more than 200 FASN-dependent acylated cellular proteins. Alk-4 also labeled the palmitoylated host protein IFITM3 (Interferon inducible transmembrane protein-3), a restriction factor for Influenza, and the myristoylated HIV-1 MA (Matrix) protein. Thus, Alk-4 is a useful bioorthogonal tool to selectively probe FASN-mediated protein acylation in normal and diseased states.
Project description:T. rubrum was treated with PH11B,a potent eucaryotic fatty acid synthase inhibtor. A cDNA microarray was constructed from the expressed sequence tags (ESTs) of different developmental stages, and transcriptional profiles of the responses to PH11B were determined. Some class-specific and mechanism-independent changes in gene expression were found. Keywords: fatty acid synthase inhibition
