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Kaichun Li, Mingzhen Ying, Dan Feng, Jie Du, Shiyu Chen, Bing Dan, Cuihua Wang, Yajie Wang
Fructose-1,6-bisphosphatase (FBP1), the rate-limiting enzyme in gluconeogenesis, is a tumor suppressor that frequently down-regulated in cancers, especially breast cancer. Here, we provide both supporting and contradicting evidences about the expression pattern and function of FBP1 in breast cancer. Data mining of Oncomine database showed that FBP1 is commonly up-regulated in tumor tissues compared with non-tumor tissues regardless of histological type. Analysis of a large-scale cohort derived from Kaplan-Meier Plotter showed that lower FBP1 expression associated with poor clinical outcome...
October 22, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Min Xie, Yan Yu, Rui Kang, Shan Zhu, Liangchun Yang, Ling Zeng, Xiaofang Sun, Minghua Yang, Timothy R Billiar, Haichao Wang, Lizhi Cao, Jianxin Jiang, Daolin Tang
Sepsis, severe sepsis and septic shock are the main cause of mortality in non-cardiac intensive care units. Immunometabolism has been linked to sepsis; however, the precise mechanism by which metabolic reprogramming regulates the inflammatory response is unclear. Here we show that aerobic glycolysis contributes to sepsis by modulating inflammasome activation in macrophages. PKM2-mediated glycolysis promotes inflammasome activation by modulating EIF2AK2 phosphorylation in macrophages. Pharmacological and genetic inhibition of PKM2 or EIF2AK2 attenuates NLRP3 and AIM2 inflammasomes activation, and consequently suppresses the release of IL-1β, IL-18 and HMGB1 by macrophages...
October 25, 2016: Nature Communications
Yung-Mei Chao, You-Lin Tain, Steve Leu, Kay L H Wu, Wei-Chia Lee, Julie Y H Chan
Excessive fructose intake is related to a high prevalence of metabolic syndrome, while little attention has been paid to the impact of maternal high-fructose (HF) intake on the development of metabolic syndrome and organ-specific transcriptome alterations in the offspring. We utilized RNA next-generation sequencing (NGS) technology to analyze the transcriptome expression in four organs (kidney, brain, heart, and urinary bladder) from 1-day, 3-week, and 3-month-old male offspring exposed to maternal HF diet...
October 25, 2016: Sheng Li Xue Bao: [Acta Physiologica Sinica]
Erin M M Weisenhorn, Thomas J Van't Erve, Nicholas M Riley, John R Hess, Thomas J Raife, Joshua J Coon
Each year over 90 million units of blood are transfused worldwide. Our dependence on this blood supply mandates optimized blood management and storage. During storage, red blood cells undergo degenerative processes resulting in altered metabolic characteristics which may make blood less viable for transfusion. However, not all stored blood spoils at the same rate, a difference that has been attributed to variable rates of energy usage and metabolism in red blood cells. Specific metabolite abundances are heritable traits; however, the link between heritability of energy metabolism and red blood cell storage profiles is unclear...
October 24, 2016: Molecular & Cellular Proteomics: MCP
Sang Hyun Hwang, Jeong Won Lee, Ho Jin Cho, Kyung Sik Kim, Gi Hong Choi, Mijin Yun
PURPOSE: The aim of this article was to evaluate the prognostic value of metabolic tumor volume (MTV) and total lesion glycolysis (TLG) on preoperative F-FDG PET/CT for predicting intrahepatic recurrence-free survival (IHRFS), extrahepatic metastasis-free survival (EHMFS), and overall survival (OS) in patients with very early/early hepatocellular carcinoma (HCC). PATIENTS AND METHODS: We retrospectively enrolled 132 patients with very early/early HCC who underwent F-FDG PET/CT followed by surgery...
October 21, 2016: Clinical Nuclear Medicine
Jari E Kaikkonen, Peter Würtz, Emmi Suomela, Miia Lehtovirta, Antti J Kangas, Antti Jula, Vera Mikkilä, Jorma S A Viikari, Markus Juonala, Tapani Rönnemaa, Nina Hutri-Kähönen, Mika Kähönen, Terho Lehtimäki, Pasi Soininen, Mika Ala-Korpela, Olli T Raitakari
: Non-alcoholic fatty liver is associated with obesity-related metabolic disturbances, but little is known about the metabolic perturbations preceding fatty liver disease. We performed comprehensive metabolic profiling to assess how circulating metabolites, such as lipoprotein lipids, fatty acids, amino acids and glycolysis-related metabolites, reflect the presence of and future risk for fatty liver in young adults. Sixty-eight lipids and metabolites were quantified by nuclear magnetic resonance metabolomics in the population-based Young Finns Study from serum collected in 2001 (n=1,575), 2007 (n=1,509) and 2011 (n=2,002)...
October 24, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
R-H Xu, B Liu, J-D Wu, Y-Y Yan, J-N Wang
OBJECTIVE: Atherosclerosis is recognized as a chronic inflammatory disease leading to hardening of the vessel wall and narrowing of arteries. Endothelial cells (ECs) exhibit highly active glycolysis, the dysfunction of which leads to accumulation of lipids in the arterial wall and formation of atherosclerotic plaque. MATERIALS AND METHODS: qRT-PCR was performed to compare the deregulated miR-143 between atherosclerotic plaque and normal vessel tissues. The direct target of miR-143 was verified by Western blot and luciferase assay...
October 2016: European Review for Medical and Pharmacological Sciences
A Blomme, B Costanza, P de Tullio, M Thiry, G Van Simaeys, S Boutry, G Doumont, E Di Valentin, T Hirano, T Yokobori, S Gofflot, O Peulen, A Bellahcène, F Sherer, C Le Goff, E Cavalier, A Mouithys-Mickalad, F Jouret, P G Cusumano, E Lifrange, R N Muller, S Goldman, P Delvenne, E De Pauw, M Nishiyama, V Castronovo, A Turtoi
Myoferlin is a multiple C2-domain-containing protein that regulates membrane repair, tyrosine kinase receptor function and endocytosis in myoblasts and endothelial cells. Recently it has been reported as overexpressed in several cancers and shown to contribute to proliferation, migration and invasion of cancer cells. We have previously demonstrated that myoferlin regulates epidermal growth factor receptor activity in breast cancer. In the current study, we report a consistent overexpression of myoferlin in triple-negative breast cancer cells (TNBC) over cells originating from other breast cancer subtypes...
October 24, 2016: Oncogene
María-Victoria Hinckelmann, Amandine Virlogeux, Christian Niehage, Christel Poujol, Daniel Choquet, Bernard Hoflack, Diana Zala, Frédéric Saudou
The glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) facilitates fast axonal transport in neurons. However, given that GAPDH does not produce ATP, it is unclear whether glycolysis per se is sufficient to propel vesicles. Although many proteins regulating transport have been identified, the molecular composition of transported vesicles in neurons has yet to be fully elucidated. Here we selectively enrich motile vesicles and perform quantitative proteomic analysis. In addition to the expected molecular motors and vesicular proteins, we find an enrichment of all the glycolytic enzymes...
October 24, 2016: Nature Communications
György Miklós Buzás
Although fructose was discovered in 1794, it was realised in recent decades only that its malabsorption can lead to intestinal symptoms while its excessive consumption induces metabolic disturbances. Fructose is a monosaccharide found naturally in most fruits and vegetables. Dietary intake of fructose has gradually increased in the past decades, especially because of the consumption of high fructose corn syrup. With its 16.4 kg/year consumption, Hungary ranks secondly after the United States. Fructose is absorbed in the small intestine by facilitated transport mediated by glucose transporter proteins-2 and -5, and arrives in the liver cells...
October 2016: Orvosi Hetilap
Hongli Hu, Wenwei Zhu, Jun Qin, Min Chen, Liyan Gong, Long Li, Xiangyuan Liu, Yongzhen Tao, Huiyong Yin, Hu Zhou, Lisha Zhou, Dan Ye, Qinghai Ye, Daming Gao
: Phosphoglycerate kinase 1(PGK1) is an important enzyme in metabolic glycolysis pathway. In this study, we observed a significant over-expression of PGK1 in liver cancer tissues and a negative correlation between PGK1 expression and liver cancer patients survival. Furthermore, depletion of PGK1 dramatically reduced cancer cell proliferation and tumorigenesis, indicating an oncogenic role of PGK1 in liver cancer progression. Moreover, we identified the acetylation at K323 site of PGK1 as an important regulatory mechanism for promoting its enzymatic activity and cancer cell metabolism...
October 24, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Hermann Koepsell
Orally applied SGLT2 (SLC5A2) inhibitors that enter the blood and decrease renal reabsorption of glucose have been approved as antidiabetic drugs. They decrease blood glucose levels, slightly reduce body weight and blood pressure, and decrease the risk for diabetic nephropathy. The SGLT2 inhibitor empagliflozin has been shown to reduce the risk of severe cardiac failure. This review summarizes knowledge about the functions of SGLT2 and the pathophysiology of type 2 diabetes (T2D) and diabetic follow-up diseases...
October 20, 2016: Pharmacology & Therapeutics
Clara Bien Peek, Daniel C Levine, Jonathan Cedernaes, Akihiko Taguchi, Yumiko Kobayashi, Stacy J Tsai, Nicolle A Bonar, Maureen R McNulty, Kathryn Moynihan Ramsey, Joseph Bass
Circadian clocks are encoded by a transcription-translation feedback loop that aligns energetic processes with the solar cycle. We show that genetic disruption of the clock activator BMAL1 in skeletal myotubes and fibroblasts increased levels of the hypoxia-inducible factor 1α (HIF1α) under hypoxic conditions. Bmal1(-/-) myotubes displayed reduced anaerobic glycolysis, mitochondrial respiration with glycolytic fuel, and transcription of HIF1α targets Phd3, Vegfa, Mct4, Pk-m, and Ldha, whereas abrogation of the clock repressors CRY1/2 stabilized HIF1α in response to hypoxia...
October 19, 2016: Cell Metabolism
Mathias Wenes, Min Shang, Mario Di Matteo, Jermaine Goveia, Rosa Martín-Pérez, Jens Serneels, Hans Prenen, Bart Ghesquière, Peter Carmeliet, Massimiliano Mazzone
Hypoxic tumor-associated macrophages (TAMs) acquire angiogenic and immunosuppressive properties. Yet it remains unknown if metabolic changes influence these functions. Here, we argue that hypoxic TAMs strongly upregulate the expression of REDD1, a negative regulator of mTOR. REDD1-mediated mTOR inhibition hinders glycolysis in TAMs and curtails their excessive angiogenic response, with consequent formation of abnormal blood vessels. Accordingly, REDD1 deficiency in TAMs leads to the formation of smoothly aligned, pericyte-covered, functional vessels, which prevents vessel leakiness, hypoxia, and metastases...
October 13, 2016: Cell Metabolism
Margaret O James, Stephan C Jahn, Guo Zhong, Marci G Smeltz, Zhiwei Hu, Peter W Stacpoole
Dichloroacetate (DCA) has several therapeutic applications based on its pharmacological property of inhibiting pyruvate dehydrogenase kinase. DCA has been used to treat inherited mitochondrial disorders that result in lactic acidosis, as well as pulmonary hypertension and several different solid tumors, the latter through its ability to reverse the Warburg effect in cancer cells and restore aerobic glycolysis. The main clinically limiting toxicity is reversible peripheral neuropathy. Although administration of high doses to rodents can result in liver cancer, there is no evidence that DCA is a human carcinogen...
October 19, 2016: Pharmacology & Therapeutics
Michael Karlsson, Johannes K Ehinger, Sarah Piel, Fredrik Sjövall, Johanna Henriksnäs, Urban Höglund, Magnus J Hansson, Eskil Elmér
Metabolic crisis is a clinical condition primarily affecting patients with inherent mitochondrial dysfunction in situations of augmented demand. To model this, ten pigs received an infusion of rotenone, a mitochondrial complex I inhibitor, or vehicle. Clinical parameters, blood gases, continuous indirect calorimetry, in vivo muscle oxygen tension, ex vivo mitochondrial respiration and metabolomics were assessed. Rotenone induced a progressive increase in lactate which was paralleled by an increase in oxygen tension in venous blood and skeletal muscle...
October 18, 2016: Mitochondrion
Ruinan Gu, Fali Zhang, Gang Chen, Chaojun Han, Jay Liu, Zhaoxiang Ren, Yi Zhu, John L Waddington, Long Tai Zheng, Xuechu Zhen
Clock (Clk)1/COQ7 is a mitochondrial hydroxylase that is necessary for the biosynthesis of ubiquinone (coenzyme Q or UQ). Here, we investigate the role of Clk1 in neuroinflammation and consequentially dopaminergic (DA) neuron survival. Reduced expression of Clk1 in microglia enhanced the LPS-induced proinflammatory response and promoted aerobic glycolysis. Inhibition of glycolysis abolished Clk1 deficiency-induced hypersensitivity to the inflammatory stimulation. Mechanistic studies demonstrated that mTOR/HIF-1α and ROS/HIF-1α signaling pathways were involved in Clk1 deficiency-induced aerobic glycolysis...
October 18, 2016: Brain, Behavior, and Immunity
Yuxin Shu, Yan Lu, Xiaojuan Pang, Wei Zheng, Yahong Huang, Jiahong Li, Jianguo Ji, Can Zhang, Pingping Shen
Peroxisome proliferator-activating receptor γ (PPARγ), a transcription factor, is involved in many important biological processes, including cell terminal differentiation, survival and apoptosis. However, the role of PPARγ, which regulates tumour promoter and oncogene expression, is not well understood in hepatocellular carcinoma (HCC). In the present study, based on evidence from clinical samples that phosphorylation of PPARγ at Ser84 is up-regulated in human liver tumours, we confirmed that phosphorylation of PPARγ was also significantly increased in an HCC mouse model and was increased by Mitogen-activated protein kinase (MEK)/ Extracellular-signal-regulated kinases (ERK) kinase...
October 19, 2016: Oncotarget
Shin Yup Lee, Cheng Cheng Jin, Jin Eun Choi, Mi Jeong Hong, Deuk Kju Jung, Sook Kyung Do, Sun Ah Baek, Hyo Jung Kang, Hyo-Gyoung Kang, Sun Ha Choi, Won Kee Lee, Yangki Seok, Eung Bae Lee, Ji Yun Jeong, Kyung Min Shin, Sukki Cho, Seung Soo Yoo, Jaehee Lee, Seung Ick Cha, Chang Ho Kim, You Mie Lee, In-Kyu Lee, Sanghoon Jheon, Jae Yong Park
This study was conducted to investigate whether polymorphisms of genes involved in glycolysis are associated with the prognosis of patients with non-small cell lung cancer (NSCLC) after surgical resection. Forty-four single nucleotide polymorphisms (SNPs) of 17 genes in glycolytic pathway were investigated in a total of 782 patients with NSCLC who underwent curative surgical resection. The association of the SNPs with overall survival (OS) and disease free survival (DFS) were analyzed. Among the 44 SNPs investigated, four SNPs (ENO1 rs2274971A > G, PFKM rs11168417C > T, PFKP rs1132173C > T, PDK2 rs3785921G > A) were significantly associated with survival outcomes in multivariate analyses...
October 21, 2016: Scientific Reports
Whitney D Hollinshead, Sarah Rodriguez, Hector Garcia Martin, George Wang, Edward E K Baidoo, Kenneth L Sale, Jay D Keasling, Aindrila Mukhopadhyay, Yinjie J Tang
BACKGROUND: Glycolysis breakdowns glucose into essential building blocks and ATP/NAD(P)H for the cell, occupying a central role in its growth and bio-production. Among glycolytic pathways, the Entner Doudoroff pathway (EDP) is a more thermodynamically favorable pathway with fewer enzymatic steps than either the Embden-Meyerhof-Parnas pathway (EMPP) or the oxidative pentose phosphate pathway (OPPP). However, Escherichia coli do not use their native EDP for glucose metabolism. RESULTS: Overexpression of edd and eda in E...
2016: Biotechnology for Biofuels
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