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Tian Liao, Yuan-Jin Wang, Jia-Qian Hu, Yu Wang, Li-Tao Han, Ben Ma, Rong-Liang Shi, Ning Qu, Wen-Jun Wei, Qing Guan, Jun Xiang, Jia-Ying Chen, Guo-Hua Sun, Duan-Shu Li, Xiang-Ming Mu, Qing-Hai Ji
KMT5A (known as PR-Set7/9, SETD8 and SET8), a member of the SET domain containing methyltransferase family specifically targeting H4K20 for methylation, has been implicated in multiple biological processes. In the present study, we identified that KMT5A was elevated in 50 pairs of papillary thyroid cancer tissue samples and in cell lines K1 and TPC-1 by qRT-PCR and western blotting, as well as by immunohistochemical staining. CCK-8 assay and flow cytometric analysis revealed that inhibition of KMT5A attenuated proliferation and induced apoptosis...
March 5, 2018: Oncology Reports
Monica A Newman, Renée M Petri, Dietmar Grüll, Qendrim Zebeli, Barbara U Metzler-Zebeli
Dietary inclusion of resistant starches can promote host health through modulation of the gastrointestinal microbiota, short-chain fatty acid (SCFA) profiles, and lipid metabolism. This study investigated the impact of a transglycosylated cornstarch (TGS) on gastric, ileal, cecal, proximal-colonic, and mid-colonic bacterial community profiles and fermentation metabolites using a growing pig model. It additionally evaluated the effect of TGS on the expression of host genes related to glucose and SCFA absorption, incretins, and satiety in the gut as well as host genes related to lipid metabolism in hepatic and adipose tissue...
2018: Frontiers in Microbiology
Bandish Kapadia, Nahid M Nanaji, Kavita Bhalla, Binny Bhandary, Rena Lapidus, Afshin Beheshti, Andrew M Evens, Ronald B Gartenhaus
Altered lipid metabolism and aberrant protein translation are strongly associated with cancerous outgrowth; however, the inter-regulation of these key processes is still underexplored in diffuse large B-cell lymphoma (DLBCL). Although fatty acid synthase (FASN) activity is reported to positively correlate with PI3K-Akt-mTOR pathway that can modulate protein synthesis, the precise impact of FASN inhibition on this process is still unknown. Herein, we demonstrate that attenuating FASN expression or its activity significantly reduces eIF4B (eukaryotic initiation factor 4B) levels and consequently overall protein translation...
February 26, 2018: Nature Communications
Santosh L Saraf, Justin R Sysol, Alexandru Susma, Suman Setty, Xu Zhang, Krishnamurthy P Gudehithlu, Jose A L Arruda, Ashok K Singh, Roberto F Machado, Victor R Gordeuk
Homozygosity for the hemoglobin (Hb) S mutation (HbSS, sickle cell anemia) results in hemoglobin polymerization under hypoxic conditions leading to vaso-occlusion and hemolysis. Sickle cell anemia affects 1:500 African Americans and is a strong risk factor for kidney disease, although the mechanisms are not well understood. Heterozygous inheritance (HbAS; sickle cell trait) affects 1:10 African Americans and is associated with an increased risk for kidney disease in some reports. Using transgenic sickle mice, we investigated the histopathologic, ultrastructural, and gene expression differences with the HbS mutation...
February 2, 2018: Translational Research: the Journal of Laboratory and Clinical Medicine
Mi-Yeon Jung, Jeong-Han Kang, Danielle M Hernandez, Xueqian Yin, Mahefatiana Andrianifahanana, Youli Wang, Anatilde Gonzalez-Guerrico, Andrew H Limper, Ruth Lupu, Edward B Leof
Evidence is provided that the fibroproliferative actions of TGF-β are dependent on a metabolic adaptation that sustains pathologic growth. Specifically, profibrotic TGF-β signaling is shown to require fatty acid synthase (FASN), an essential anabolic enzyme responsible for the de novo synthesis of fatty acids. With the use of pharmacologic and genetic approaches, we show that TGF-β-stimulated FASN expression is independent of Smad2/3 and is mediated via mammalian target of rapamycin complex 1. In the absence of FASN activity or protein, TGF-β-driven fibrogenic processes are reduced with no apparent toxicity...
February 16, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Meiqiang Chu, Yong Zhao, Shuai Yu, Yanan Hao, Pengfei Zhang, Yanni Feng, Hongfu Zhang, Dongxue Ma, Jing Liu, Ming Cheng, Lan Li, Wei Shen, Hongfang Cao, Qiang Li, Lingjiang Min
Milk lipids, important for infant growth and development, are produced and secreted by mammary gland under the regulation of steroid hormones, growth factors, and microRNAs (miRNAs). miR-221 has been identified in milk and adipocytes and it plays important roles in regulating normal mammary epithelial hierarchy and breast cancer stem cells; however, its roles in lipid metabolism in mammary epithelial cells (MECs), the cells of lipid synthesis and secretion, are as yet unknown. Through overexpression or inhibition of miR-221 expression, we found that it regulated lipid metabolism in MECs and was expressed differentially at various stages during murine mammary gland development...
February 20, 2018: International Journal of Biochemistry & Cell Biology
Jackie K W Chan, Stefanie Bittner, Alex Bittner, Suman Atwal, Wen-Jun Shen, Mohammed Inayathullah, Jayakumar Rajada, Mark R R Nicolls, Fredric B Kraemer, Salman Azhar
To determine the effects of NDGA on metabolic and molecular changes in response to feeding mice typical American fast food or Western diet, mice were fed with ALIOS diet and subjected to metabolic analysis. Male C57BL/6J mice were randomly assigned to: ALIOS, ALIOS + NDGA, or control diet and maintained on the specific diet for 8 weeks. Mice fed ALIOS diet, showed increased body, liver and epididymal fat pad weight, plasma ALT and AST levels (a measure of liver injury), and liver triglyceride (TG) content. Co-administration of NDGA normalized body and epididymal fat pad weight, ALT and AST levels, and liver TG...
February 22, 2018: Journal of Pharmacology and Experimental Therapeutics
Laura Galbraith, Hing Y Leung, Imran Ahmad
The link between prostate cancer (PC) development and lipid metabolism is well established, with AR intimately involved in a number of lipogenic processes involving SREBP1, PPARG, FASN, ACC, ACLY and SCD1. Recently, there is growing evidence implicating the role of obesity and peri-prostatic adipose tissue (PPAT) in PC aggressiveness and related mortality, suggesting the importance of lipid pathways in both localised and disseminated disease. A number of promising agents are in development to target the lipogenic axis in PC, and the likelihood is that these agents will form part of combination drug strategies, with targeting of multiple metabolic pathways (e...
February 18, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Yong Liu, Patrick L Leslie, Aiwen Jin, Koji Itahana, Lee M Graves, Yanping Zhang
Sustained endoplasmic reticulum (ER) stress plays a major role in the development of many metabolic diseases, including cardiovascular disease, nonalcoholic fatty liver disease, insulin resistance, obesity, and diabetes. p32 is a multicompartmental protein involved in the regulation of oxidative phosphorylation and glucose oxidation. p32 ablation is associated with resistance to age-associated and diet-induced obesity through a mechanism that remains largely unknown. Here, we show that p32 promotes lipid biosynthesis by modulating fatty acid-induced ER stress...
February 20, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Richard G Carroll, Zbigniew Zaslona, Silvia Galván-Peña, Emma L Koppe, Daniel C Sévin, Stefano Angiari, Martha Triantafilou, Kathy Triantafilou, Louise K Modis, Luke O'Neill
Different immune activation states require distinct metabolic features and activities in immune cells. For instance, inhibition of fatty acid synthase (FASN), which catalyzes the synthesis of long-chain fatty acids, prevents the proinflammatory response in macrophages; however, the precise role of this enzyme in this response remains poorly defined. Consistent with previous studies, we found here that FASN is essential for lipopolysaccharide-induced, Toll-like receptor (TLR)-mediated macrophage activation. Interestingly, only agents that block FASN upstream of acetoacetyl-CoA synthesis, including the well-characterized FASN inhibitor C75, inhibited TLR4 signaling, while those acting downstream had no effect...
February 20, 2018: Journal of Biological Chemistry
Bao-Long Pan, Zong-Wu Tong, Ling Wu, Li Pan, Jun-E Li, You-Guang Huang, Shu-De Li, Shi-Xun Du, Xu-Dong Li
BACKGROUND/AIMS: This study aimed to investigate the mechanism by which microRNA-206 (miR-206) affects the proliferation, apoptosis, migration and invasion of osteosarcoma (OS) cells by targeting ANXA2 via the AKT signaling pathway. METHODS: A total of 132 OS tissues and 120 osteochondroma tissues were examined in this study. The targeting relationship between miR-206 and ANXA2 was verified with a dual-luciferase reporter assay. The miR-206 expression and ANXA2, AKT, PARP, FASN, Survivin, Bax, Mcl-1 and Bcl-1 mRNA and protein expression in the above two groups were examined by qRT-PCR and western blotting...
February 15, 2018: Cellular Physiology and Biochemistry
B Renaville, N Bacciu, M Lanzoni, F Mossa, E Piasentier
Dietary and organoleptic qualities of pork products are largely influenced by the profiles of fatty acids (FAs) of meat and fat. The objective of this work was to investigate the potential associations between FA profile in subcutaneous adipose (back fat and leg fat) and muscular (longissimus dorsi and biceps femoris) tissues in heavy pigs (n = 129, 9-month-old) with single nucleotide polymorphisms (SNPs) in six candidate genes involved in fat metabolism: Stearoyl-CoA desaturase (SCD), Diacylglycerol acyltransferase 1 and 2 (DGAT1 &DGAT2), Microsomal Triglyceride Transfer Protein (MTTP), Fatty Acid Synthase (FASN) and Heart- fatty acid binding protein (H-FABP)...
February 7, 2018: Meat Science
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
Weiwei Wang, Xiaona Zhang, Zihao Wang, Jingyu Qin, Wei Wang, Hua Tian, Shaoguo Ru
It has been suggested that dramatic increase in obesity may be caused by growing exposure to environmental chemicals. In vitro data has suggested bisphenol S (BPS), a compound widely used in polycarbonate plastic production, can induce lipid accumulation in preadipocytes. However, the mechanisms responsible for BPS-induced obesity in vivo remain unclear. In this study, we used translucent zebrafish (Danio rerio) larvae as a model to investigate the effect of environmentally relevant BPS exposure (1, 10, and 100 μg/L from 2 h to 15 d post fertilization) on lipid accumulation, triacylglycerol (TAG) and lipoproteins content, and mRNA expression of genes involved in the regulation of lipid synthesis, transport, degradation, and storage...
February 3, 2018: Chemosphere
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
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
Linda Saxe Einbond, Fabiana Manservisi, Hsan-Au Wu, Michael Balick, Victoria Antonetti, Andrea Vornoli, Ilaria Menghetti, Fiorella Belpoggi, Stephen Redenti, Alan Roter
The spice turmeric (Curcuma longa L.) has a long history of use as an anti-inflammatory agent. The active component curcumin induces a variety of diverse biological effects and forms a series of degradation and metabolic products in vivo. Our hypothesis is that the field of toxicogenomics provides tools that can be used to characterize the mode of action and toxicity of turmeric components and to predict turmeric-drug interactions. Male Sprague-Dawley rats were treated for 4 days with turmeric root containing about 3% curcumin (comparable to what people consume in the fresh or dried root) or a fraction of turmeric enriched for curcumin (∼74%) and liver tissue collected for gene expression analysis...
February 3, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Shanshan Zhang, Xiaoxing Li, Hui-Yun Wang, X F Steven Zheng
MAF1 was discovered as a master repressor of Pol III-dependent transcription in response to diverse extracellular signals, including growth factor, nutrient and stress. It is regulated through posttranslational mechanisms such as phosphorylation. A prominent upstream regulator of MAF1 is the mechanistic target of rapamycin (mTOR) pathway. mTOR kinase directly phosphorylates MAF1, controlling its localization and transcriptional activity. In mammals, MAF1 has also been shown to regulate Pol I- and Pol II-dependent transcription...
January 30, 2018: Biochimica et Biophysica Acta
Tim Martin Knutsen, Hanne Gro Olsen, Valeria Tafintseva, Morten Svendsen, Achim Kohler, Matthew Peter Kent, Sigbjørn Lien
The relative abundance of specific fatty acids in milk can be important for consumer health and manufacturing properties of dairy products. Understanding of genes controlling milk fat synthesis may contribute to the development of dairy products with high quality and nutritional value. This study aims to identify key genes and genetic variants affecting de novo synthesis of the short- and medium-chained fatty acids C4:0 to C14:0. A genome-wide association study using 609,361 SNP markers and 1,811 animals was performed to detect genomic regions affecting fatty acid levels...
February 1, 2018: Scientific Reports
Linjie Wang, Ke Xue, Yan Wang, Lili Niu, Li Li, Tao Zhong, Jiazhong Guo, Jing Feng, Tianzeng Song, Hongping Zhang
Objective: It is commonly accepted that adiponectin binds to its two receptors to regulate fatty acid metabolism in adipocytes. To better understand their functions in the regulation of intramuscular adipogenesis in goats, we cloned the three genes (AdipoQ, AdipoR1 and AdipoR2) encoding these proteins and detected their mRNA distribution in different tissues. We also determined the role of AdipoQ in the adipogenic differentiation of goat skeletal muscle satellite cells (SMSCs). Methods: SMSCs were isolated using 1 mg/ml Pronase E from the longissimus dorsi muscles of 3-day-old female Nanjiang brown goats...
January 30, 2018: Asian-Australasian Journal of Animal Sciences
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