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ATP-citrate lyase

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
Amy C Burke, Dawn E Telford, Brian G Sutherland, Jane Y Edwards, Cynthia G Sawyez, P Hugh R Barrett, Roger S Newton, J Geoffrey Pickering, Murray W Huff
OBJECTIVE: Bempedoic acid (BemA; ETC-1002) is a novel drug that targets hepatic ATP-citrate lyase to reduce cholesterol biosynthesis. In phase 2 studies, BemA lowers elevated low-density lipoprotein cholesterol (LDL-C) in hypercholesterolemic patients. In the present study, we tested the ability of BemA to decrease plasma cholesterol and LDL-C and attenuate atherosclerosis in a large animal model of familial hypercholesterolemia. APPROACH AND RESULTS: Gene targeting has been used to generate Yucatan miniature pigs heterozygous ( LDLR +/- ) or homozygous ( LDLR -/- ) for LDL receptor deficiency (ExeGen)...
February 15, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
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
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
Mitsuru Imamura, Jong-Seok Moon, Kuei-Pin Chung, Kiichi Nakahira, Thangamani Muthukumar, Roman Shingarev, Stefan W Ryter, Augustine Mk Choi, Mary E Choi
Renal fibrosis is a common pathogenic response to injury in chronic kidney disease (CKD). The receptor-interacting protein kinase-3 (RIPK3), a regulator of necroptosis, has been implicated in disease pathogenesis. In mice subjected to unilateral ureteral obstruction-induced (UUO-induced) or adenine diet-induced (AD-induced) renal fibrosis, models of progressive kidney fibrosis, we demonstrate increased kidney expression of RIPK3. Mice genetically deficient in RIPK3 displayed decreased kidney fibrosis and improved kidney function relative to WT mice when challenged with UUO or AD...
February 8, 2018: JCI Insight
Haisen Li, Vittorio Sartorelli
Intermediates generated in several metabolic processes are used to regulate transcription through covalent histone and DNA modifications. In Cell Reports, Das et al. show that acetyl-coenzyme A (acetyl-CoA) generated by ATP citrate lyase (ACL) is utilized to acetylate histone H3 at MyoD regulatory regions, resulting in increased MyoD expression and improved muscle regeneration after injury.
January 30, 2018: Trends in Endocrinology and Metabolism: TEM
Shou-Cheng Huang, Shu-Juan Chu, Yu-Min Guo, Ya-Jing Ji, Dong-Qing Hu, Jing Cheng, Gui-Hua Lu, Rong-Wu Yang, Cheng-Yi Tang, Jin-Liang Qi, Yong-Hua Yang
Aluminium (Al) toxicity is one of the most important limiting factors for crop yield in acidic soils. However, the mechanisms that confer Al tolerance still remain largely unknown. To understand the molecular mechanism that confers different tolerance to Al, we performed global transcriptome analysis to the roots and leaves of two contrasting soybean genotypes, BX10 (Al-tolerant) and BD2 (Al-sensitive) under 0 and 50 μM Al3+ treatments, respectively. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses revealed that the expression levels of the genes involved in lipid/carbohydrate metabolism and jasmonic acid (JA)-mediated signalling pathway were highly induced in the roots and leaves of both soybean genotypes...
November 2017: AoB Plants
Udhayakumar Gopal, Salvatore V Pizzo
Acetyl coenzyme A (acetyl-CoA) is essential for histone acetylation, to promote cell proliferation by regulating gene expression. However, the underlying mechanism(s) governing acetylation remains poorly understood. Activated α2-Macroglobulin (α2M*) signals through tumor Cell Surface GRP78 (CS-GRP78) to regulate tumor cell proliferation through multiple signaling pathway. Here, we demonstrate that the α2M*/CS-GRP78 axis regulates acetyl-CoA synthesis and thus functions as an epigenetic modulator by enhancing histone acetylation in cancer cells...
December 8, 2017: Oncotarget
Suman Das, Frederic Morvan, Giulio Morozzi, Benjamin Jourde, Giulia C Minetti, Peter Kahle, Helene Rivet, Pascale Brebbia, Gauthier Toussaint, David J Glass, Mara Fornaro
ATP citrate lyase (ACL) plays a key role in regulating mitochondrial function, as well as glucose and lipid metabolism in skeletal muscle. We report here that ACL silencing impairs myoblast and satellite cell (SC) differentiation, and it is accompanied by a decrease in fast myosin heavy chain isoforms and MYOD. Conversely, overexpression of ACL enhances MYOD levels and promotes myogenesis. Myogenesis is dependent on transcriptional but also other mechanisms. We show that ACL regulates the net amount of acetyl groups available, leading to alterations in acetylation of H3(K9/14) and H3(K27) at the MYOD locus, thus increasing MYOD expression...
December 12, 2017: Cell Reports
Joshua Flees, Hossein Rajaei-Sharifabadi, Elizabeth Greene, Lesleigh Beer, Billy M Hargis, Laura Ellestad, Tom Porter, Annie Donoghue, Walter G Bottje, Sami Dridi
Heat stress (HS) has been reported to alter fat deposition in broilers, however the underlying molecular mechanisms are not well-defined. The objectives of the current study were, therefore: (1) to determine the effects of acute (2 h) and chronic (3 weeks) HS on the expression of key molecular signatures involved in hepatic lipogenic and lipolytic programs, and (2) to assess if diet supplementation with dried Noni medicinal plant (0.2% of the diet) modulates these effects. Broilers (480 males, 1 d) were randomly assigned to 12 environmental chambers, subjected to two environmental conditions (heat stress, HS, 35°C vs...
2017: Frontiers in Physiology
Yong-Jik Lee, Yoo-Na Jang, Yoon-Mi Han, Hyun-Min Kim, Jong-Min Jeong, Min Jeoung Son, Chang Bae Jin, Hyoung Ja Kim, Hong Seog Seo
Aster glehni is well known for its therapeutic properties. This study was performed to investigate the effects of A. glehni on nonalcoholic fatty liver disease (NAFLD) in atherosclerotic condition, by determining the levels of biomarkers related to lipid metabolism and inflammation in serum, liver, and adipose tissue. Body and abdominal adipose tissue weights and serum triglyceride level decreased in all groups treated with A. glehni . Serum adiponectin concentration and protein levels of peroxisome proliferator-activated receptor δ , 5' adenosine monophosphate-activated protein kinase, acetyl-CoA carboxylase, superoxide dismutase, and PPAR γ coactivator 1-alpha in liver tissues increased in the groups treated with A...
2017: PPAR Research
Nolwenn Callac, Nicole R Posth, Jayne E Rattray, Kweku K Y Yamoah, Alan Wiech, Magnus Ivarsson, Christoffer Hemmingsson, Stephanos P Kilias, Ariadne Argyraki, Curt Broman, Henrik Skogby, Rienk H Smittenberg, Ernest Chi Fru
The seafloor sediments of Spathi Bay, Milos Island, Greece, are part of the largest arsenic-CO2-rich shallow submarine hydrothermal ecosystem on Earth. Here, white and brown deposits cap chemically distinct sediments with varying hydrothermal influence. All sediments contain abundant genes for autotrophic carbon fixation used in the Calvin-Benson-Bassham (CBB) and reverse tricaboxylic acid (rTCA) cycles. Both forms of RuBisCO, together with ATP citrate lyase genes in the rTCA cycle, increase with distance from the active hydrothermal centres and decrease with sediment depth...
October 31, 2017: Scientific Reports
Stephen L Pinkosky, Pieter H E Groot, Narendra D Lalwani, Gregory R Steinberg
Chronic overnutrition and a sedentary lifestyle promote imbalances in metabolism, often manifesting as risk factors for life-threating diseases such as atherosclerotic cardiovascular disease (ASCVD) and nonalcoholic fatty liver disease (NAFLD). Nucleocytosolic acetyl-coenzyme A (CoA) has emerged as a central signaling node used to coordinate metabolic adaptations in response to a changing nutritional status. ATP-citrate lyase (ACL) is the enzyme primarily responsible for the production of extramitochondrial acetyl-CoA and is thus strategically positioned at the intersection of nutrient catabolism and lipid biosynthesis...
November 2017: Trends in Molecular Medicine
Patricia Pereira Nunes, Sandra Andreotti, Flaviane de Fátima Silva, Rogério Antonio Laurato Sertié, Rennan de Oliveira Caminhotto, Ayumi Cristina Medeiros Komino, Gabriela Boltes Reis, Fabio Bessa Lima
AIM: Most studies developed to investigate the effects of glucocorticoids chronic treatment on white adipose tissue uses high doses of these hormones. This study analyzes some effects of a chronic, continuous and steady infusion of low-dose hydrocortisone and the relationship with lipid accumulation in white adipose depots in rats. MAIN METHODS: Nineteen male Wistar rats were divided into control (CON) and cortisol (CORT) groups. Along six weeks CORT group received continuous infusion of 0...
December 1, 2017: Life Sciences
Longlong Li, Mengling Peng, Chongyang Ge, Lei Yu, Haitian Ma
BACKGROUND/AIMS: (-)-Hydroxycitric acid (HCA) had been shown to suppress fat accumulation in animals and humans, while the underlying biochemical mechanism is not fully understood, especially little information is available on whether (-)-HCA regulates energy metabolism and consequently affects fat deposition. METHODS: Hepatocytes were cultured for 24 h and then exposed to (-)-HCA (0, 1, 10, 50 µM), enzyme protein content was determined by ELISA; lipid metabolism gene mRNA levels were detected by RT-PCR...
2017: Cellular Physiology and Biochemistry
Chen Chen, Chenlong Li, Ying Wang, Justin Renaud, Gang Tian, Shrikaar Kambhampati, Behnaz Saatian, Vi Nguyen, Abdelali Hannoufa, Frédéric Marsolais, Ze-Chun Yuan, Kangfu Yu, Ryan S Austin, Jun Liu, Susanne E Kohalmi, Keqiang Wu, Shangzhi Huang, Yuhai Cui
Acetyl-coenzyme A (acetyl-CoA) is a central metabolite and the acetyl source for protein acetylation, particularly histone acetylation that promotes gene expression. However, the effect of acetyl-CoA levels on histone acetylation status in plants remains unknown. Here, we show that malfunctioned cytosolic acetyl-CoA carboxylase1 (ACC1) in Arabidopsis leads to elevated levels of acetyl-CoA and promotes histone hyperacetylation predominantly at lysine 27 of histone H3 (H3K27). The increase of H3K27 acetylation (H3K27ac) is dependent on adenosine triphosphate (ATP)-citrate lyase which cleaves citrate to acetyl-CoA in the cytoplasm, and requires histone acetyltransferase GCN5...
October 2017: Nature Plants
Catalina Arroyave, Roser Tolrà, Livia Chaves, Marcelo Claro de Souza, Juan Barceló, Charlotte Poschenrieder
The mechanisms of extreme Al-resistance in Urochloa decumbens are not established. Full resistance expression requires a lag time of 72-96h and is preceded by a sensitive phase (24-48h) with Al-induced root growth inhibition. The aim here was to identify key processes of the activation phase of Al-resistance analysing both root exudates and comparative root proteome. Samples were taken after 0, 24 and 96h exposure to 0 or 200μM Al. Al-induced stimulation of citrate and oxalate efflux was limited to the sensitive phase...
September 10, 2017: Journal of Inorganic Biochemistry
Yunsheng Cheng, Benli Jia, Yong Wang, Shengyun Wan
MicroRNAs (miRNAs/miRs) are a class of small noncoding RNAs that negatively regulate protein expression by binding to protein-coding mRNAs and suppressing translation. Accumulating evidence suggests that miRNAs are involved in the development and progression of cancer by regulating cancer metabolism. Meanwhile, the cytosolic enzyme ATP citrate lyase (ACLY) is a promising target in the prevention and treatment of cancer. In the present study we revealed by western blot analysis and reverse transcription‑quantitative PCR that miR-133b was downregulated in human gastric cancer (GC) tissues and cell lines, while ACLY was upregulated...
November 2017: Oncology Reports
Dingdong Zhang, Yanan Yan, Hongyan Tian, Guangzhen Jiang, Xiangfei Li, Wenbin Liu
Here, we aimed to investigate whether resveratrol (RSV) can ameliorate high-fat diet (HFD)-induced metabolic disorder in fish. Blunt snout bream (Megalobrama amblycephala) with average weight 27.99 ± 0.56 g were fed a normal fat diet (NFD, 5% fat, w/w), a HFD (11% fat), or a HFD supplemented with 0.04, 0.36, or 1.08% RSV for 10 weeks. As expected, fish fed a HFD developed hepatic steatosis, as shown by elevated hepatic and plasma triglycerides, raised whole body fat, intraperitoneal fat ratio and hepatosomatic index, and increased plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST)...
September 10, 2017: Fish Physiology and Biochemistry
Lucas Carminatti Pantaleão, Gilson Murata, Caio Jordão Teixeira, Tanyara Baliani Payolla, Junia Carolina Santos-Silva, Daniella Esteves Duque-Guimaraes, Frhancielly S Sodré, Camilo Lellis-Santos, Juliana Camargo Vieira, Dailson Nogueira de Souza, Patrícia Rodrigues Gomes, Sandra Campos Rodrigues, Gabriel Forato Anhe, Silvana Bordin
We investigated the effect of dexamethasone during the last week of pregnancy on glucose and lipid metabolism in male offspring. Twelve-week old offspring were evaluated after fasting for 12-hours (physiological) and 60-hours (prolonged). Physiological fasting resulted in glucose intolerance, decreased glucose clearance after pyruvate load and increased PEPCK expression in rats born to dexamethasone-treated mothers (DEX). Prolonged fasting resulted in increased glucose tolerance and increased glucose clearance after pyruvate load in DEX...
September 4, 2017: Scientific Reports
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