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Zainaguli Junjvlieke, Chu-Gang Mei, Rajwali Khan, Wen-Zhen Zhang, Jie-Yun Hong, Li Wang, Shi-Jun Li, Lin-Sen Zan
The elongation of very long chain fatty acids protein 6 (ELOVL6) gene encodes a key enzyme that plays a role in lipogenesis through the catalytic elongation of both saturated and monounsaturated fatty acids. Previous studies have described the high expression of bovine ELOVL6 in adipose tissues. However, transcriptional regulation and the functional role of ELOVL6 in lipid metabolism and adipocyte proliferation remain unexplored. Here, a 1.5 kb fragment of the 5'-untranslated region promoter region of ELOVL6 was amplified from the genomic DNA of Qinchuan cattle and sequenced...
April 4, 2019: Journal of Cellular Biochemistry
Hyo-Bum Kwak, Tracey L Woodlief, Thomas D Green, Julie H Cox, Robert C Hickner, P Darrell Neufer, Ronald N Cortright
In rodent skeletal muscle, acyl-coenzyme A (CoA) synthetase 5 (ACSL-5) is suggested to localize to the mitochondria but its precise function in human skeletal muscle is unknown. The purpose of these studies was to define the role of ACSL-5 in mitochondrial fatty acid metabolism and the potential effects on insulin action in human skeletal muscle cells (HSKMC). Primary myoblasts isolated from vastus lateralis (obese women (body mass index (BMI) = 34.7 ± 3.1 kg/m²)) were transfected with ACSL-5 plasmid DNA or green fluorescent protein (GFP) vector (control), differentiated into myotubes, and harvested (7 days)...
March 31, 2019: International Journal of Environmental Research and Public Health
Chao Zhao, Guangshuai Liu, Shuai Shang, Qinguo Wei, Lei Zhang, Tian Xia, Xiufeng Yang, Guolei Sun, Honghai Zhang
Carnivores exhibit various fat contents and energy reserves to adapt to their environments. However, the molecular mechanisms underlying lipid metabolic differences among carnivores have not been well explored. Long-chain acyl-CoA synthetases (ACSLs) catalyze the initial step in lipid metabolism by activating fatty acids (FAs), and they drive acyl-CoAs toward anabolic lipid synthesis or catabolic β-oxidation. We identified the sequences of the genes of the ACSL family (ACSL1, ACSL3, ACSL4, ACSL5 and ACSL6) in the sable (Martes zibellina) via transcriptome sequencing...
March 13, 2019: Genetica
Fatema Al-Rashed, Zunair Ahmad, Mina Amin Iskandar, Jaakko Tuomilehto, Fahd Al-Mulla, Rasheed Ahmad
BACKGROUND/AIMS: TNF-α-mediated pro-inflammatory phenotypic change in monocytes is known to be implicated in the pathogenesis of metabolic inflammation and insulin resistance. However, the mechanism by which TNF-α-induces inflammatory phenotypic shift in monocytes is poorly understood. Since long-chain acyl-CoA synthetase 1 (ACSL1) is associated with inflammatory monocytes/macrophages, we investigated the role of ACSL1 in the TNF-α-driven inflammatory phenotypic shift in the monocytes...
2019: Cellular Physiology and Biochemistry
Sigal Ben-Zaken, Yoav Meckel, Dan Nemet, Eias Kassem, Alon Eliakim
Ben-Zaken, S, Meckel, Y, Nemet, D, Kassem, E, and Eliakim, A. Genetic basis for the dominance of Israeli long-distance runners of Ethiopian origin. J Strength Cond Res XX(X): 000-000, 2018-Israeli long-distance runners of Ethiopian origin have a major influence on the track and field long-distance record table. The aim of this study was to determine whether genetic characteristics contribute to this long-distance dominance. We assessed polymorphisms in genes related to endurance (PPARD T/C), endurance trainability (ACSL A/G), speed (ACTN3 R/X), strength (AGT T/C), and the recovery from training (MTC1 A/T and IL6 G/C) among top Israeli long-distance runners of Ethiopian origin (n = 37), Israeli non-Ethiopian origin runners of Caucasian origin (n = 76), and Israeli nonathletic controls (n = 55)...
February 6, 2019: Journal of Strength and Conditioning Research
Rosalind A Coleman
Diet, hormones, gene transcription, and post-translational modifications control the hepatic metabolism of FAs; metabolic dysregulation causes chronic diseases, including cardiovascular disease, and warrants exploration into the mechanisms directing FA and triacylglycerol (TAG) synthesis and degradation. Long-chain FA metabolism begins by formation of an acyl-CoA by a member of the acyl-CoA synthetase family (ACSL). Subsequently, TAG synthesis begins with acyl-CoA esterification to glycerol-3-phosphate by a member of the glycerol-3-phosphate acyltransferase (GPAT) family...
January 25, 2019: Journal of Lipid Research
Mingyue Jia, Danqing Meng, Mo Chen, Tingting Li, Yong Q Zhang, Aiyu Yao
Mutations in long-chain acyl-CoA synthetase 4 (ACSL4) are associated with non-syndromic X-linked intellectual disability (ID). However, the neural functions of ACSL4 and how loss of ACSL4 leads to ID remain largely unexplored. We report here that mutations in Acsl, the Drosophila ortholog of human ACSL3 and ACSL4, result in developmental defects of the mushroom body (MB), the center of olfactory learning and memory. Specifically, Acsl mutants show fewer MB neuroblasts (Nbs) due to reduced proliferation activity and premature differentiation...
December 26, 2018: Journal of Genetics and Genomics
Sujeong Park, Jinjoo Oh, Minhee Kim, Eun-Jung Jin
Here, we investigated the possible anti-cancer properties of bromelain in Kras mutant human colorectal carcinoma cell lines and a mouse model harboring a Kras mutation. Cell growth and proliferation were significantly reduced in the Kras mutant colorectal carcinoma cell lines following treatment with 50 μg/mL bromelain as assessed by crystal violet staining and a proliferation assay. To identify the molecules responsible for this action, the expression levels of genes involved in signaling pathways and miRNAs were analyzed by real-time PCR...
2018: Animal Cells and Systems
Ishita Bakshi, Simon H J Brown, Amanda E Brandon, Eurwin Suryana, Todd W Mitchell, Nigel Turner, Gregory J Cooney
Increased lipid metabolism in muscle is associated with insulin resistance and therefore, many strategies have been employed to alter fatty acid metabolism and study the impact on insulin action. Metabolism of fatty acid requires activation to fatty acyl CoA by Acyl CoA synthases (ACSL) and fatty acyl CoA can be hydrolysed by Acyl CoA thioesterases (Acot). Thioesterase activity is low in muscle, so we overexpressed Acot7 in muscle of chow and high-fat diet (HFD) rats and investigated effects on insulin action...
September 18, 2018: Scientific Reports
Pamela A Young, Can E Senkal, Amanda L Suchanek, Trisha J Grevengoed, Dennis D Lin, Liyang Zhao, Amanda E Crunk, Eric L Klett, Joachim Füllekrug, Lina M Obeid, Rosalind A Coleman
Fatty acid channeling into oxidation or storage modes depends on physiological conditions and hormonal signaling. However, the directionality of this channeling may also depend on the association of each of the five acyl-CoA synthetase isoforms with specific protein partners. Long-chain acyl-CoA synthetases (ACSLs) catalyze the conversion of long-chain fatty acids to fatty acyl-CoAs, which are then either oxidized or used in esterification reactions. In highly oxidative tissues, ACSL1 is located on the outer mitochondrial membrane (OMM) and directs fatty acids into mitochondria for β-oxidation...
October 26, 2018: Journal of Biological Chemistry
Hong-Liang Kong, Ai-Jie Hou, Ning-Ning Liu, Bo-Han Chen, Sheng-Nan Dai, Hua-Ting Huang
Objectives: This study intended to investigate the effects of Ginsenoside-Rbl (Gs-Rbl) on fatty acid β-oxidation (FAO) in rat failing heart and to identify potential mechanisms of Gs-Rbl improving heart failure (HF) by FAO pathway dependent on AMP-activated protein kinase (AMPK). Materials and Methods: Rats with chronic HF, induced by adriamycin ( Adr ), were randomly grouped into 7 groups. Gs-Rb1, adenine 9-β-D-arabinofuranoside ( Ara A , specific AMPK inhibitor), and 5'-aminoimidazole-4-carboxamide riboside ( Aicar , specific AMPK activator) were administered to rats with HF, singly and/or combinedly...
July 2018: Iranian Journal of Basic Medical Sciences
Kuan-Ting Liu, I-Jeng Yeh, Shih-Kai Chou, Meng-Chi Yen, Po-Lin Kuo
The endoplasmic reticulum (ER) is an organelle involved in various physiological processes such as lipid metabolism, protein synthesis and folding, and cellular calcium storage. In a physiological tumor microenvironment, hypoxia, nutrient deprivation, and calcium dysregulation cause accumulation of unfolded and misfolded proteins. Such accumulation induces ER stress and unfolded protein responses (UPRs). Increased UPR signaling pathways are associated with multiple types of cancer. The influence of ER stress on acyl‑CoA metabolic enzymes is not well understood...
November 2018: Oncology Reports
Yue Tang, Jing Zhou, Shing Chuan Hooi, Yue-Ming Jiang, Guo-Dong Lu
The significance of fatty acid metabolism in cancer initiation and development is increasingly accepted by scientists and the public due to the high prevalence of overweight and obese individuals. Fatty acids have different turnovers in the body: Either breakdown into acetyl-CoA to aid ATP generation through catabolic metabolism or incorporation into triacylglycerol and phospholipid through anabolic metabolism. However, these two distinct pathways require a common initial step known as fatty acid activation...
August 2018: Oncology Letters
Karla Acosta-Virgen, Bibiana Chávez-Munguía, Daniel Talamás-Lara, Anel Lagunes-Guillén, Aaron Martínez-Higuera, Antonio Lazcano, Adolfo Martínez-Palomo, Martha Espinosa-Cantellano
The protozoan parasite Giardia lamblia has traditionally been reported as lacking peroxisomes, organelles involved in fatty acid metabolism and detoxification of reactive oxygen species. We here report the finding with transmission electron microscopy of an oxidase activity in cytoplasmic vesicles of trophozoites and cysts of G. lamblia. These vesicles were positive to 3,3'-diaminobenzidine and to cerium chloride staining. In addition, using bioinformatic tools, two peroxisomal proteins were identified in the G...
August 2018: Experimental Parasitology
Yu-Feng Song, Xiao-Ying Tan, Ya-Xiong Pan, Li-Han Zhang, Qi-Liang Chen
Although several studies have been conducted to study leptin function, information is very scarce on the molecular mechanism of leptin in fatty acid β-oxidation and oocytes maturation in fish. In this study, we investigated the potential role of fatty acid β-oxidation in leptin-mediated oocytes maturation in Pelteobagrus fulvidraco . Exp. 1 investigated the transcriptomic profiles of ovary and the differential expression of genes involved in β-oxidation and oocytes maturation following rt-hLEP injection; rt-hLEP injection was associated with significant changes in the expression of genes, including twenty-five up-regulated genes ( CPT1 , Acsl , Acadl , Acadm , Hadhb , Echsl , Hsd17b4 , Acca , PPARα , CYP8B1 , ACOX1 , ACBP , MAPK , RINGO , Cdc2 , MEK1 , IGF-1R , APC/C, Cdk2 , GnRHR, STAG3 , SMC1 , FSHβ and C-Myc ) and ten down-regulated gene ( PPARγ , FATCD36 , UBC , PDK1 , Acads , Raf , Fizzy , C3H-4 , Raf and PKC ), involved in fatty acid β-oxidation and oocytes maturation...
May 14, 2018: International Journal of Molecular Sciences
David Grünig, Andrea Felser, Urs Duthaler, Jamal Bouitbir, Stephan Krähenbühl
Tolcapone and entacapone are catechol-O-methyltransferase inhibitors used in patients with Parkinson's disease. For tolcapone, patients with liver failure have been reported with microvesicular steatosis observed in the liver biopsy of 1 patient. We therefore investigated the impact of tolcapone and entacapone on fatty acid metabolism in HepaRG cells exposed for 24 h and on acutely exposed mouse liver mitochondria. In HepaRG cells, tolcapone induced lipid accumulation starting at 100 µM, whereas entacapone was ineffective up to 200 µM...
August 1, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
Florencia Pascual, Jonathan C Schisler, Trisha J Grevengoed, Monte S Willis, Rosalind A Coleman
BACKGROUND: Long-chain acyl-CoA synthetases (ACSL) catalyze the conversion of long-chain fatty acids to fatty acyl-CoAs. Cardiac-specific ACSL1 temporal knockout at 2 months results in a shift from FA oxidation toward glycolysis that promotes mTORC1-mediated ventricular hypertrophy. We used unbiased metabolomics and gene expression analyses to examine the early effects of genetic inactivation of fatty acid oxidation on cardiac metabolism, hypertrophy development, and function. METHODS AND RESULTS: Global cardiac transcriptional analysis revealed differential expression of genes involved in cardiac metabolism, fibrosis, and hypertrophy development in Acsl1 H-/- hearts 2 weeks after Acsl1 ablation...
April 5, 2018: Journal of the American Heart Association
Paige V Bauer, Frank A Duca, T M Zaved Waise, Helen J Dranse, Brittany A Rasmussen, Akshita Puri, Mozhgan Rasti, Catherine A O'Brien, Tony K T Lam
Long-chain acyl-CoA synthetase (ACSL)-dependent upper small intestinal lipid metabolism activates pre-absorptive pathways to regulate metabolic homeostasis, but whether changes in the upper small intestinal microbiota alter specific fatty acid-dependent pathways to impact glucose homeostasis remains unknown. We here first find that upper small intestinal infusion of Intralipid, oleic acid, or linoleic acid pre-absorptively increases glucose tolerance and lowers glucose production in rodents. High-fat feeding impairs pre-absorptive fatty acid sensing and reduces upper small intestinal Lactobacillus gasseri levels and ACSL3 expression...
March 6, 2018: Cell Metabolism
Yassmeen Radif, Haarith Ndiaye, Vasiliki Kalantzi, Ruth Jacobs, Andrew Hall, Shane Minogue, Mark G Waugh
Fatty acid uptake and metabolism are often dysregulated in cancer cells. Fatty acid activation is a critical step that allows these biomolecules to enter cellular metabolic pathways such as mitochondrial β-oxidation for ATP generation or the lipogenic routes that generate bioactive lipids such as the inositol phospholipids. Fatty acid activation by the addition of coenzyme A is catalysed by a family of enzymes called the acyl CoA synthetase ligases (ACSL). Furthermore, enhanced expression of particular ACSL isoforms, such as ACSL4, is a feature of some more aggressive cancers and may contribute to the oncogenic phenotype...
November 2018: Molecular and Cellular Biochemistry
Eric Soupene, Frans A Kuypers
De novo lipid synthesis and scavenging of fatty acids (FA) are processes essential for the formation of the membrane of the human pathogen Chlamydia trachomatis (C.t.). Host FA are assimilated via esterification by the bacterial acyl-acyl carrier protein (ACP) synthase AasC but inhibitors of the host acyl-CoA synthetase enymes ACSL also impaired growth of C.t. in human cells. In E. coli, activity of AasC was sensitive to triacsin C and rosiglitazone G. The absence of a triacsin C-insensitive pathway and the increased inhibition by rosiglitazone G confirmed the sensitivity of the bacterial acyl-ACP synthase to these drugs in infected human cells...
November 17, 2017: Scientific Reports
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