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Yuji Nishiura, Akira Matsumura, Naotake Kobayashi, Atsuyuki Shimazaki, Shingo Sakamoto, Naohisa Kitade, Yutaka Tonomura, Akira Ino, Takayuki Okuno
Novel acetyl-CoA carboxylase 2 (ACC2) selective inhibitors were identified by the conversion of the alkyne unit of A-908292 to the olefin linker. Modification of the center and left part of the lead compound 1b improved the ACC2 inhibitory activity and CYP450 inhibition profile, and afforded a highly selective ACC2 inhibitor 2e which showed in vivo efficacy in C57BL/6 mice.
June 4, 2018: Bioorganic & Medicinal Chemistry Letters
Yun Chen, Shiyu Zheng, Zhenzhen Ju, Chengqi Zhang, Guangfei Tang, Jing Wang, Ziyue Wen, Wei Chen, Zhonghua Ma
Peroxisomal proliferation is highly stimulated during the biosynthesis of mycotoxins and plant infection by Fusarium graminearum. Currently, the functions of the peroxisome in these cellular processes are poorly understood. In this study, we applied genetic, cell biological and biochemical analyses to investigate the functions of the peroxisomes. We constructed targeted deletion of docking machinery components, including FgPex13, FgPex14 and the filamentous fungal specific peroxin FgPex33. Our results indicated that peroxisome dysfunction resulted in a shortage of acetyl-CoA, the precursor of trichothecene biosynthesis, and subsequently decreased deoxynivalenol (DON) production...
June 14, 2018: Environmental Microbiology
Moritz Hunkeler, Anna Hagmann, Edward Stuttfeld, Mohamed Chami, Yakir Guri, Henning Stahlberg, Timm Maier
Acetyl-CoA carboxylase catalyses the ATP-dependent carboxylation of acetyl-CoA, a rate-limiting step in fatty acid biosynthesis1,2 . Eukaryotic acetyl-CoA carboxylases are large, homodimeric multienzymes. Human acetyl-CoA carboxylase occurs in two isoforms: the metabolic, cytosolic ACC1, and ACC2, which is anchored to the outer mitochondrial membrane and controls fatty acid β-oxidation1,3 . ACC1 is regulated by a complex interplay of phosphorylation, binding of allosteric regulators and protein-protein interactions, which is further linked to filament formation1,4-8 ...
June 13, 2018: Nature
Raphael Ferreira, Paulo Gonçalves Teixeira, Michael Gossing, Florian David, Verena Siewers, Jens Nielsen
Triacylglycerols (TAGs) are valuable versatile compounds that can be used as metabolites for nutrition and health, as well as feedstocks for biofuel production. Although Saccharomyces cerevisiae is the favored microbial cell factory for industrial production of biochemicals, it does not produce large amounts of lipids and TAGs comprise only ~1% of its cell dry weight. Here, we engineered S. cerevisiae to reorient its metabolism for overproduction of TAGs, by regulating lipid droplet associated-proteins involved in TAG synthesis and hydrolysis...
June 2018: Metabolic Engineering Communications
Alfonso Olaya-Abril, Jesús Hidalgo-Carrillo, Víctor M Luque-Almagro, Carlos Fuentes-Almagro, Francisco J Urbano, Conrado Moreno-Vivián, David J Richardson, María D Roldán
Denitrification is a respiratory process that produces nitrous oxide as an intermediate, which may escape to the atmosphere before its reduction to dinitrogen through the nitrous oxide reductase NosZ. In this work, the denitrification process carried out by Paracoccus denitrificans PD1222 has been explored through a quantitative proteomic analysis. Under anaerobic conditions, with nitrate as sole nitrogen source, the synthesis of all the enzymes involved in denitrification, the respiratory nitrate, nitrite, nitric oxide, and nitrous oxide reductases, was increased...
2018: Frontiers in Microbiology
(no author information available yet)
No abstract text is available yet for this article.
June 11, 2018: Proceedings of the National Academy of Sciences of the United States of America
Lile Dong, Xu Han, Xufeng Tao, Lina Xu, Youwei Xu, Linlin Fang, Lianhong Yin, Yan Qi, Hua Li, Jinyong Peng
We previously reported the effects of the total flavonoids (TFs) from Rosa laevigata Michx fruit against carbon tetrachloride-induced liver damage, non-alcoholic fatty liver disease, and liver ischemia-reperfusion injury. However, there have been no papers reporting the role of R. laevigata TFs against lipopolysaccharide (LPS)-induced liver injury. In this paper, liver injury in mice was induced by LPS, and R. Laevigata extract was intragastrically administered to the mice for 7 days. Biochemical parameters in serum and liver tissue were examined, and pathological changes were observed by transmission electron microscopy, hematoxylin and eosin (H&E) and Oil Red O staining...
June 8, 2018: Foods (Basel, Switzerland)
Shivani Garg, Hao Wu, James M Clomburg, George N Bennett
Methane, the primary component of natural gas, is the second most abundant greenhouse gas (GHG) and contributes significantly to climate change. The conversion of methane to industrial platform chemicals provides an attractive opportunity to decrease GHG emissions and utilize this inexpensive and abundantly available gas as a carbon feedstock. While technologies exist for chemical conversion of methane to liquid fuels, the technical complexity of these processes mandate high capital expenditure, large-scale commercial facilities to leverage economies of scale that cannot be efficiently scaled down...
June 5, 2018: Metabolic Engineering
He Wen, Sujin Lee, Wei-Guo Zhu, Ok-Jun Lee, Seok Joong Yun, Jayoung Kim, Sunghyouk Park
Cisplatin is an important chemotherapeutic agent against metastatic bladder cancer, but resistance often limits its usage. With the recent recognition of lipid metabolic alterations in bladder cancers, we studied the metabolic implications of cisplatin resistance using cisplatin-sensitive (T24S) and resistant (T24R) bladder cancer cells. Real-time live metabolomics revealed that T24R cells consume more glucose, leading to higher production of glucose-derived acetate and fatty acids. Along with the activation of general metabolic regulators, enzymes involved in acetate usage (ACSS2) and fatty acid synthesis (ACC) and a precursor for fatty acid synthesis (acetyl-CoA) were elevated in T24R cells...
June 5, 2018: Biochimica et Biophysica Acta
Kelly A Markham, Hal S Alper
The oleaginous yeast Yarrowia lipolytica is quickly emerging as the most popular non-conventional (i.e., non-model organism) yeast in the bioproduction field. With a high propensity for flux through tricarboxylic acid (TCA) cycle intermediates and biological precursors such as acetyl-CoA and malonyl-CoA, this host is especially well suited to meet our industrial chemical production needs. Recent progress in synthetic biology tool development has greatly enhanced our ability to rewire this organism, with advances in genetic component design, CRISPR technologies, and modular cloning strategies...
June 4, 2018: Trends in Biotechnology
Haitao Pan, Chuhan Fu, Lanlan Huang, Yao Jiang, Xiaoyi Deng, Jiao Guo, Zhengquan Su
Obesity is a global disease that causes many metabolic disorders. However, effective agents for the prevention or treatment of obesity remain limited. This study investigated the anti-obesity effect and mechanism of chitosan oligosaccharide capsules (COSCs) on rats suffering from obesity induced by a high-fat diet (HFD). After the eight-week administration of COSCs on obese rats, the body weight gain, fat/body ratio, and related biochemical indices were measured. The hepatic expressions of the leptin signal pathway (JAK2-STAT3) and gene expressions of adipogenesis-related targets were also determined...
June 5, 2018: Marine Drugs
Toshihiro Aoyagi, Masaya Kobayashi, Akiko Kozaki
Increasing the yield of plant oil is an important objective to meet the demand for sustainable resources and energy. Some attempts to enhance the expression of genes involved in oil synthesis in seeds have succeeded in increasing oil content. In many cases, the promoters of seed-storage protein genes have been used as seed-specific promoters. However, conventional promoters are developmentally regulated and their expression periods are limited. We constructed a chimeric promoter that starts to express in the early stage of seed development, and high-level expression is retained until the later stage by connecting the promoters of the biotin carboxyl carrier protein 2 ( BCCP2 ) gene encoding the BCCP2 subunit of acetyl-CoA carboxylase and the fatty acid elongase 1 ( FAE1 ) gene from Arabidopsis ...
June 5, 2018: International Journal of Molecular Sciences
Sneha Sundaram, Petr Žáček, Michael R Bukowski, Aaron A Mehus, Lin Yan, Matthew J Picklo
Metabolic reprogramming of lipid metabolism is a hallmark of cancer. Consumption of a high-fat obesogenic diet enhances spontaneous metastasis using a Lewis lung carcinoma (LLC) model. In order to gain further insights into the mechanisms by which dietary fats impact cancer progression, we conducted a lipidomic analysis of primary tumors originated from LLC from mice fed with a standard AIN93G diet or a soybean oil-based high-fat diet (HFD). Hierarchical clustering heatmap analysis of phosphatidylcholine (PC) lipids and phosphatidylethanolamine (PE) lipids demonstrated an increase in polyunsaturated fatty acids (PUFA)-containing phospholipids and a decrease in monounsaturated fatty acids (MUFA)-containing lipids in tumors from mice fed the HFD...
2018: Frontiers in Oncology
Jie Hao, Kaipeng Huang, Cheng Chen, Yan Liang, Yu Wang, Xiaojian Zhang, Heqing Huang
Previous investigations on diabetic rats and palmitic corrosive instigated insulin-resistant HepG2 cells have shown that polydatin exhibits hypoglycemic and hypolipidemic impacts. The AMP-activated protein kinase (AMPK) pathway assumes a crucial part in glucose and lipid digestion. We aimed to investigate the regulatory system of polydatin on the glucose and lipid metabolism through the AMPK pathway. Glucose take-up, utilization levels, and oil red O recoloring were distinguished to confirm their impact on improving insulin resistance...
2018: Biological & Pharmaceutical Bulletin
Xiao-Lin Meng, Shuai Li, Chao-Bin Qin, Zhen-Xiang Zhu, Wen-Pan Hu, Li-Ping Yang, Rong-Hua Lu, Wen-Jun Li, Guo-Xing Nie
The present study was conducted to determine the effects of waterborne copper exposure on the lipid metabolism and intestinal microbiota of juvenile common carp (Cyprinus carpio L.). Common carp were exposed to four waterborne copper (Cu) concentrations (0 (control), 0.07 (low), 0.14 (medium), and 0.28 (high) mg Cu/L) for 8 weeks. Exposure to a high concentration of Cu had a negative effect on growth indices (weight gain rate (WGR) and specific growth rate (SGR)). The biochemical indices measured in serum (low-density lipoprotein (LDL) and triglycerides (TGs)) were significantly affected by exposure to medium concentration levels of Cu...
May 28, 2018: Ecotoxicology and Environmental Safety
Huifen Xu, Jun Luo, Huibin Tian, Jun Li, Xueying Zhang, Zhi Chen, Ming Li, Juan J Loor
In mammals, sterol regulatory element binding protein-1 (SREBP-1) is the master regulator of fatty acid and triacylglycerol synthesis. Recent gene silencing studies in mammary cells indicate that SREBP-1 has a central role in milk fat synthesis. However, SREBP-1 knockdown studies in goat mammary cells have not been performed; hence, its direct role in controlling mRNA expression of lipid metabolism genes and triacylglycerol synthesis remains unknown. Inhibition of SREBP-1 in goat mammary epithelial cells (GMEC) by small interference RNA (siRNA) markedly reduced the content of cellular triacylglycerol (~50% decrease, P < 0...
May 28, 2018: Journal of Animal Science
Kwanseob Shim, Sheila Jacobi, Jack Odle, Xi Lin
Up-regulation of peroxisome proliferator-activating receptor-α (PPARα) and increasing fatty acid oxidation are important for reducing pre-weaning mortality of pigs. We examined the time-dependent regulatory effects of PPARα activation via oral postnatal clofibrate administration (75 mg/(kg-BW·d) for up to 7 days) on mitochondrial and peroxisomal fatty acid oxidation in pigs, a species with limited hepatic fatty acid oxidative capacity due to low ketogenesis. Hepatic oxidation was increased by 44-147% (depending on fatty acid chain-length) and was attained after only 4 days of clofibrate treatment...
May 8, 2018: Oncotarget
Md Wasimul Haque, Pritha Bose, Mohd Usman Mohd Siddique, Priyashree Sunita, Antonio Lapenna, Shakti P Pattanayak
AIM: 7,12-dimethylbenz(a)anthracene(DMBA), a PAH derivative initializes cascades of signaling events that alters a variety of enzymes responsible for lipid and glucose homeostasis resulting in enhanced availability and consumption of energy producing molecules for the development of carcinogenesis. 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoAR) is a key enzyme regulating the pathway of synthesis of cholesterol whereas liver-X-receptor (LXR) regulates lipid, carbohydrate metabolism in various malignancies including mammary carcinogenesis (MC)...
May 26, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Yoann Millerioux, Muriel Mazet, Guillaume Bouyssou, Stefan Allmann, Tiila-Riikka Kiema, Eloïse Bertiaux, Laetitia Fouillen, Chandan Thapa, Marc Biran, Nicolas Plazolles, Franziska Dittrich-Domergue, Aline Crouzols, Rik K Wierenga, Brice Rotureau, Patrick Moreau, Frédéric Bringaud
De novo biosynthesis of lipids is essential for Trypanosoma brucei, a protist responsible for the sleeping sickness. Here, we demonstrate that the ketogenic carbon sources, threonine, acetate and glucose, are precursors for both fatty acid and sterol synthesis, while leucine only contributes to sterol production in the tsetse fly midgut stage of the parasite. Degradation of these carbon sources into lipids was investigated using a combination of reverse genetics and analysis of radio-labelled precursors incorporation into lipids...
May 29, 2018: PLoS Pathogens
Alexander T Eprintsev, Dmitry N Fedorin, Maria A Dobychina, Abir U Igamberdiev
Expression of genes encoding the mitochondrial and peroxisomal forms of citrate synthase (EC was studied in maize (Zea mays L.) in scutella during germination and in leaves depending on light regime. During germination, citrate synthase activity increased in scutella both in mitochondria and in fatty-acid metabolizing peroxisomes (glyoxysomes) by day 6 and then declined. This was preceded by the peak of expression of the genes encoding the mitochondrial (Csy1) and peroxisomal (Csy2) forms of citrate synthase occurring on the day 3 of germination, after which the expression of Csy1 gradually and of Csy2 sharply declined...
July 2018: Plant Science: An International Journal of Experimental Plant Biology
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