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Fatty acid synthase

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https://www.readbyqxmd.com/read/29449607/6-thioguanine-is-a-noncompetitive-and-slow-binding-inhibitor-of-human-deubiquitinating-protease-usp2
#1
Shang-Ju Chuang, Shu-Chun Cheng, Hui-Chi Tang, Chiao-Yin Sun, Chi-Yuan Chou
Ubiquitin-specific protease 2 (USP2) belongs to the family of deubiquitinases that can rescue protein targets from proteasomal degradation by reversing their ubiquitination. In various cancers, including prostate cancer and ovarian carcinoma, upregulation of USP2 leads to an increase in the levels of deubiquitinated substrates such as fatty acid synthase, MDM2, cyclin D1 and Aurora-A. USP2 thus plays a critical role in tumor cells' survival and therefore represents a therapeutic target. Here a leukemia drug, 6-thioguanine, was found to be a potent inhibitor of USP2...
February 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29449592/first-evidence-for-a-multienzyme-complex-of-lipid-biosynthesis-pathway-enzymes-in-cunninghamella-bainieri
#2
Shuwahida Shuib, Izyanti Ibrahim, Mukram Mohamed Mackeen, Colin Ratledge, Aidil Abdul Hamid
Malic enzyme (ME) plays a vital role in determining the extent of lipid accumulation in oleaginous fungi being the major provider of NADPH for the activity of fatty acid synthase (FAS). We report here the first direct evidence of the existence of a lipogenic multienzyme complex (the lipid metabolon) involving ME, FAS, ATP: citrate lyase (ACL), acetyl-CoA carboxylase (ACC), pyruvate carboxylase (PC) and malate dehydrogenase (MDH) in Cunninghamella bainieri 2A1. Cell-free extracts prepared from cells taken in both growth and lipid accumulation phases were prepared by protoplasting and subjected to Blue Native (BN)-PAGE coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS)...
February 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29449326/fatty-acid-synthase-mediates-egfr-palmitoylation-in-egfr-mutated-non-small-cell-lung-cancer
#3
Azhar Ali, Elena Levantini, Jun Ting Teo, Julian Goggi, John G Clohessy, Chan Shuo Wu, Leilei Chen, Henry Yang, Indira Krishnan, Olivier Kocher, Junyan Zhang, Ross A Soo, Kishore Bhakoo, Tan Min Chin, Daniel G Tenen
Metabolic reprogramming is widely known as a hallmark of cancer cells to allow adaptation of cells to sustain survival signals. In this report, we describe a novel oncogenic signaling pathway exclusively acting in mutated epidermal growth factor receptor (EGFR) non-small cell lung cancer (NSCLC) with acquired tyrosine kinase inhibitor (TKI) resistance. Mutated EGFR mediates TKI resistance through regulation of the fatty acid synthase (FASN), which produces 16-C saturated fatty acid palmitate. Our work shows that the persistent signaling by mutated EGFR in TKI-resistant tumor cells relies on EGFR palmitoylation and can be targeted by Orlistat, an FDA-approved anti-obesity drug...
February 15, 2018: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/29441719/azd1208-a-pan-pim-kinase-inhibitor-inhibits-adipogenesis-and-induces-lipolysis-in-3t3-l1-adipocytes
#4
Yu-Kyoung Park, Brice Wilfried Obiang-Obounou, Kyung-Bok Lee, Jong-Soon Choi, Byeong-Churl Jang
The proviral integration moloney murine leukaemia virus (Pim) kinases, consisting of Pim-1, Pim-2 and Pim-3, are involved in the control of cell growth, metabolism and differentiation. Pim kinases are emerging as important mediators of adipocyte differentiation. AZD1208 is a pan-Pim kinase inhibitor and is known for its anti-cancer activity. In this study, we investigated the effect of AZD1208 on adipogenesis and lipolysis in 3T3-L1 cells, a murine preadipocyte cell line. AZD1208 markedly suppressed lipid accumulation and reduced triglyceride contents in differentiating 3T3-L1 cells, suggesting the drug's anti-adipogenic effect...
February 14, 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29440395/fatty-acid-binding-protein-5-controls-microsomal-prostaglandin-e-synthase-1-mpges-1-induction-during-inflammation
#5
Diane Bogdan, Jerome Falcone, Martha P Kanjiya, Sang Hoon Park, Gregory Carbonetti, Keith Studholme, Maria Gomez, Yong Lu, Matthew W Elmes, Norbert Smietalo, Su Yan, Iwao Ojima, Michelino Puopolo, Martin Kaczocha
Fatty acid binding proteins (FABPs) are intracellular lipid carriers that regulate inflammation, and pharmacological inhibition of FABP5 reduces inflammation and pain. The mechanism(s) underlying the anti-inflammatory effects associated with FABP5 inhibition are poorly understood. Herein, we identify a novel mechanism through which FABP5 modulates inflammation. In mice, intraplantar injection of carrageenan induces acute inflammation that is accompanied by edema, enhanced pain sensitivity, and elevations in pro-inflammatory cytokines and prostaglandin E2 (PGE2)...
February 13, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29434927/upregulation-of-pyruvate-kinase-m2-expression-by-fatty-acid-synthase-contributes-to-gemcitabine-resistance-in-pancreatic-cancer
#6
Shenghua Tian, Pingping Li, Shi Sheng, Xin Jin
Pancreatic cancer has one of the highest mortality rates of all cancer types. Fatty acid synthase (FASN) is a multifunctional protein homodimer that can convert acetyl coenzyme A (CoA) and malonyl-CoA into palmitate, thus regulating lipogenesis. FASN overexpression has also been shown to cause resistance to gemcitabine, a chemotherapy treatment for pancreatic cancer; however, the mechanism by which this happens is unclear. Analysis of gene expression of FASN and pyruvate kinase M2 (PKM2) in pancreatic cancer was performed using Oncomine microarray gene expression datasets, which demonstrated that FASN and PKM2 were upregulated in pancreatic cancer compared with normal tissue...
February 2018: Oncology Letters
https://www.readbyqxmd.com/read/29434648/hsp90%C3%AE-knockdown-in-dio-mice-reverses-insulin-resistance-and-improves-glucose-tolerance
#7
Enxuan Jing, Pragalath Sundararajan, Ishita Deb Majumdar, Suwagmani Hazarika, Samantha Fowler, Angela Szeto, Stephane Gesta, Armando J Mendez, Vivek K Vishnudas, Rangaprasad Sarangarajan, Niven R Narain
Background: Inhibition of Hsp90 has been shown to improve glucose tolerance and insulin sensitivity in mouse models of diabetes. In the present report, the specific isoform Hsp90ab1, was identified as playing a major role in regulating insulin signaling and glucose metabolism. Methods: In a diet-induced obese (DIO) mouse model of diabetes, expression of various Hsp90 isoforms in skeletal tissue was examined. Subsequent experiments characterized the role of Hsp90ab1 isoform in glucose metabolism and insulin signaling in primary human skeletal muscle myoblasts (HSMM) and a DIO mouse model...
2018: Nutrition & Metabolism
https://www.readbyqxmd.com/read/29434029/de-novo-fatty-acid-synthesis-by-schwann-cells-is-essential-for-peripheral-nervous-system-myelination
#8
Laura Montani, Jorge A Pereira, Camilla Norrmén, Hartmut B F Pohl, Elisa Tinelli, Martin Trötzmüller, Gianluca Figlia, Penelope Dimas, Belinda von Niederhäusern, Rachel Schwager, Sebastian Jessberger, Clay F Semenkovich, Harald C Köfeler, Ueli Suter
Myelination calls for a remarkable surge in cell metabolism to facilitate lipid and membrane production. Endogenous fatty acid (FA) synthesis represents a potentially critical process in myelinating glia. Using genetically modified mice, we show that Schwann cell (SC) intrinsic activity of the enzyme essential for de novo FA synthesis, fatty acid synthase (FASN), is crucial for precise lipid composition of peripheral nerves and fundamental for the correct onset of myelination and proper myelin growth. Upon FASN depletion in SCs, epineurial adipocytes undergo lipolysis, suggestive of a compensatory role...
February 6, 2018: Journal of Cell Biology
https://www.readbyqxmd.com/read/29432553/short-term-heat-stress-altered-metabolism-and-insulin-signaling-in-skeletal-muscle
#9
Shanthi Ganesan, Corey M Summers, Sarah C Pearce, Nicholas K Gabler, Rudy J Valentine, Lance H Baumgard, Robert P Rhoads, Joshua T Selsby
Heat-related complications continue to be a major health concern for humans and animals and lead to potentially life-threatening conditions. Heat stress (HS) alters metabolic parameters and may alter glucose metabolism and insulin signaling. Therefore, the purpose of this investigation was to determine the extent to which 12 h of HS altered energetic metabolism in oxidative skeletal muscle. To address this, crossbred gilts (n=8/group) were assigned to one of three environmental treatments for 12 h: thermoneutral (TN; 21° C), heat stress (HS; 37° C), or pair-fed to HS counterparts but housed in TN conditions (PFTN)...
February 8, 2018: Journal of Animal Science
https://www.readbyqxmd.com/read/29428667/silybum-marianum-oil-attenuates-hepatic-steatosis-and-oxidative-stress-in-high-fat-diet-fed-mice
#10
Shu Yun Zhu, Ning Jiang, Jing Yang, Jie Tu, Yue Zhou, Xiang Xiao, Ying Dong
In the present study, the effects of Silybum marianum oil (SMO) on hepatic steatosis and oxidative stress were investigated during the development of nonalcoholic fatty liver disease (NAFLD) in high fat diet (HFD)-fed mice. The results showed that body weight, fat mass, and serum biochemical parameters such as triglyceride, free fatty acid, glucose and insulin were reduced by SMO treatment. Meanwhile, SMO decreased the histological injury of liver and the levels of hepatic triglyceride, cholesterol and free fatty acid in HFD-fed mice...
February 8, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29428619/effect-of-dietary-n-3-polyunsaturated-fatty-acid-rich-fish-oil-on-the-endometrial-prostaglandin-production-in-the-doe-capra-hircus
#11
Ravjibhai K Chaudhari, Ajit Singh Mahla, Amit Kumar Singh, Sanjay Kumar Singh, Abhijit M Pawde, G V P P S Ravi Kumar, GyanendraSingh, Mihir Sarkar, Harendra Kumar, Krishnaswamy Narayanan
Recently, we showed that dietary supplementation of n-3 PUFA rich fish oil (FO) decreased the metabolites of serum prostaglandin (PG) F 2α and E 2 during the window of pregnancy recognition in the doe. In this study, we investigated its effect on the changes on endometrial PG production in vitro. Cycling does (n = 12) of Rohilkhand region were divided into two equal groups and fed a concentrate diet supplemented with either FO containing 26% n-3 PUFA (TRT; n = 6) or palm oil (CON; n = 6) @ 0.6 mL/kg body weight for 57 days...
February 8, 2018: Prostaglandins & Other Lipid Mediators
https://www.readbyqxmd.com/read/29428005/effects-of-branched-chain-volatile-fatty-acids-on-lactation-performance-and-mrna-expression-of-genes-related-to-fatty-acid-synthesis-in-mammary-gland-of-dairy-cows
#12
Q Liu, C Wang, G Guo, W J Huo, S L Zhang, C X Pei, Y L Zhang, H Wang
Branched-chain volatile fatty acids (BCVFA) supplements could promote lactation performance and milk quality by improving ruminal fermentation and milk fatty acid synthesis. This study was conducted to evaluate the effects of BCVFA supplementation on milk performance, ruminal fermentation, nutrient digestibility and mRNA expression of genes related to fatty acid synthesis in mammary gland of dairy cows. A total of 36 multiparous Chinese Holstein cows averaging 606±4.7 kg of BW, 65±5.2 day in milk (DIM) with daily milk production of 30...
February 12, 2018: Animal: An International Journal of Animal Bioscience
https://www.readbyqxmd.com/read/29426861/deficiency-of-a-triterpene-pathway-results-in-humidity-sensitive-genic-male-sterility-in-rice
#13
Zheyong Xue, Xia Xu, Yuan Zhou, Xiaoning Wang, Yingchun Zhang, Dan Liu, Binbin Zhao, Lixin Duan, Xiaoquan Qi
In flowering plants, the pollen coat protects the released male germ cells from desiccation and damage during pollination. However, we know little about the mechanism by which the chemical composition of the pollen coat prevents dehydration of pollen grains. Here we report that deficiency of a grass conserved triterpene synthase, OsOSC12/OsPTS1, in rice leads to failure of pollen coat formation. The mutant plants are male sterile at low relative humidity (RH < 60%), but fully male fertile at high relative humidity (>80%)...
February 9, 2018: Nature Communications
https://www.readbyqxmd.com/read/29424268/bacterial-quorum-sensing-in-symbiotic-and-pathogenic-relationships-with-hosts
#14
Kenji Kai
Gram-negative bacteria communicate with each other by producing and sensing diffusible signaling molecules. This mechanism is called quorum sensing (QS) and regulates many bacterial activities from gene expression to symbiotic/pathogenic interactions with hosts. Therefore, the elucidation and control of bacterial QS systems have been attracted increasing attention over the past two decades. The most common QS signals in Gram-negative bacteria are N-acyl homoserine lactones (AHLs). There are also bacteria that employ different QS systems, for example, the plant pathogen Ralstonia solanacearum utilizes 3-hydroxy fatty acid methyl esters as its QS signals...
February 9, 2018: Bioscience, Biotechnology, and Biochemistry
https://www.readbyqxmd.com/read/29423634/critical-steps-in-carbon-metabolism-affecting-lipid-accumulation-and-their-regulation-in-oleaginous-microorganisms
#15
REVIEW
Marianna Dourou, Dimitra Aggeli, Seraphim Papanikolaou, George Aggelis
Oleaginous microorganisms are able to convert numerous agro-industrial and municipal wastes into storage lipids (single cell oil (SCO)) and are therefore considered as potential biofuel producers. While from an environmental and technological point of view the idea to convert waste materials into fuels is very attractive, the production cost of SCO is not currently competitive to that of conventional oils due to the low productivity of oleaginous microorganisms in combination with the high fermentation cost...
February 8, 2018: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/29423081/pm2-5-inhalation-induces-intracranial-atherosclerosis-which-may-be-ameliorated-by-omega-3-fatty-acids
#16
Longfei Guan, Xiaokun Geng, Jiamei Shen, James Yip, Fengwu Li, Huishan Du, Zhili Ji, Yuchuan Ding
Background: Intracranial atherosclerosis (ICA) a major health problem. This study investigated whether inhalation of fine airborne particulate matters (PM2.5) causes ICA and whether omega-3 fatty acids (O3FA) attenuated the development of ICA. Results: Twelve but not 6 week exposure significantly increased triglycerides (TG) in normal chow diet (NCD), while PM2.5 enhanced all lipid profiles (TG, low density lipoprotein (LDL) and cholesterol (CHO)) after both 6 and 12-week exposure with high-cholesterol diet (HCD)...
January 9, 2018: Oncotarget
https://www.readbyqxmd.com/read/29419789/aged-oolong-tea-reduces-high-fat-diet-induced-fat-accumulation-and-dyslipidemia-by-regulating-the-ampk-acc-signaling-pathway
#17
Erdong Yuan, Xuefei Duan, Limin Xiang, Jiaoyan Ren, Xingfei Lai, Qiuhua Li, Lingli Sun, Shili Sun
While oolong tea (OT) has been shown to induce weight loss and reduce fat accumulation, the mechanisms remain poorly defined, especially for aged OT. In this study, five groups of mice (n = 9/group) were used including a normal diet with vehicle treatment, and a high-fat diet (HFD) with vehicle or the water extracts from aged OTs (EAOTs, three different storage years) by oral gavage at 1000 mg/kg·BW for 6 weeks. Body weight, fat accumulation, and serum biochemical parameters were used to evaluate obesity. The morphology of hepatocytes and adipocytes was analyzed by being stained with hematoxylin and eosin...
February 8, 2018: Nutrients
https://www.readbyqxmd.com/read/29414770/homocysteine-regulates-fatty-acid-and-lipid-metabolism-in-yeast
#18
Myriam Visram, Maja Radulovic, Sabine Steiner, Nermina Malanovic, Thomas O Eichmann, Heimo Wolinski, Gerald N Rechberger, Oksana Tehlivets
S-adenosyl-L-homocysteine hydrolase (AdoHcy hydrolase; Sah1 in yeast/AHCY in mammals) degrades AdoHcy, a byproduct and strong product inhibitor of S-adenosyl-L-methionine (AdoMet)-dependent methylation reactions, to adenosine and homocysteine (Hcy). This reaction is reversible, so any elevation of Hcy levels, such as in hyperhomocysteinemia (HHcy), drives the formation of AdoHcy, with detrimental consequences for cellular methylation reactions. HHcy, a pathological condition linked to cardiovascular and neurological disorders as well as fatty liver amongst others, is associated with a deregulation of lipid metabolism...
February 6, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29411984/two-fungicides-alter-reproduction-of-the-small-brown-planthopper-laodelphax-striatellus-by-influencing-gene-and-protein-expression
#19
You Wu, Jun Ding, Bing Xu, Linlin You, Linquan Ge, Guoqing Yang, Fang Liu, David Stanley, Qisheng Song, Jincai Wu
Aside from their intended actions, fungicides can drive pest insect outbreaks and, due to virtually continuous use, evolution. Small brown planthopper (SBPH), Laodelphax striatellus, outbreaks occurred recently in many provinces in China, with devastating rice losses.Because exposure to the fungicide jinggangmycin(JGM) increased reproduction of the brown plant hopper, Nilaparvata lugens, via its influence on fatty acid synthase, we posed the hypothesis that JGM and CBM influence SBPH reproduction via their influence on enzymes involved in other aspects of lipid metabolism...
February 7, 2018: Journal of Proteome Research
https://www.readbyqxmd.com/read/29409806/vitamin-a-deficiency-induces-endoplasmic-reticulum-stress-and-apoptosis-in-pancreatic-islet-cells-implications-of-stearoyl-coa-desaturase-1-mediated-oleic-acid-synthesis
#20
M Raja Gopal Reddy, S Mullapudi Venkata, U K Putcha, S M Jeyakumar
Previously, we reported that vitamin A deficiency resulted in the reduction of stearoyl-CoA desaturase 1 (SCD1) and monounsaturated fatty acid (MUFA) levels, which corroborated with attenuation of high fructose-induced hepatic steatosis. Here, we aimed at assessing the effect of vitamin A deficiency on SCD1, MUFA levels and their impact on pancreas' structure and functions. Male weanling Wistar rats fed one of the four diets, namely control (Con), vitamin A-deficient (VAD), highfructose (HFr) and vitamin A-deficient diet with highfructose (VADHFr) for 16 weeks period...
February 1, 2018: Experimental Cell Research
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