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AMPK energy metabolism

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https://www.readbyqxmd.com/read/28108519/survival-of-acute-monocytic-leukemia-cells-is-driven-by-fatty-acid-oxidation-mediated-activation-of-ampk-in-bone-marrow-adipocytes
#1
Yoko Tabe, Shinichi Yamamoto, Kaori Saitoh, Kazumasa Sekihara, Norikazu Monma, Kazuho Ikeo, Kaoru Mogushi, Masato Shikami, Vivian R Ruvolo, Jo Ishizawa, Numsen Hail, Saiko Kazuno, Mamoru Igarashi, Hiromichi Matsushita, Yasunari Yamanaka, Hajime Arai, Isao Nagaoka, Takashi Miida, Yoshihide Hayashizaki, Marina Konopleva, Michael Andreeff
Leukemia cells in the bone marrow (BM) must meet the biochemical demands of increased cell proliferation by continually adapting to fluctuations in nutrient and oxygen availability. Thus, targeting metabolic abnormalities in leukemia cells located in the BM may provide an effective therapeutic strategy. In this study, we report the discovery of a metabolic role for BM adipocytes in supporting the growth of leukemic blasts. Preventing nutrient starvation-induced apoptosis of leukemic cells by BM adipocytes, as well as the metabolic and molecular mechanisms involved in this process, were investigated using various analytical techniques...
January 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/28107516/liver-amp-activated-protein-kinase-is-unnecessary-for-gluconeogenesis-but-protects-energy-state-during-nutrient-deprivation
#2
Clinton M Hasenour, D Emerson Ridley, Freyja D James, Curtis C Hughey, E Patrick Donahue, Benoit Viollet, Marc Foretz, Jamey D Young, David H Wasserman
AMPK is an energy sensor that protects cellular energy state by attenuating anabolic and promoting catabolic processes. AMPK signaling is purported to regulate hepatic gluconeogenesis and substrate oxidation; coordination of these processes is vital during nutrient deprivation or pathogenic during overnutrition. Here we directly test hepatic AMPK function in regulating metabolic fluxes that converge to produce glucose and energy in vivo. Flux analysis was applied in mice with a liver-specific deletion of AMPK (L-KO) or floxed control littermates to assess rates of hepatic glucose producing and citric acid cycle (CAC) fluxes...
2017: PloS One
https://www.readbyqxmd.com/read/28093038/metabonomic-strategy-to-the-evaluation-of-chinese-medicine-salvia-miltiorrhiza-and-dalbergia-odorifera-interfering-myocardial-ischemia-reperfusion-injury-in-rats
#3
Fei Mu, Jialin Duan, Haixu Bian, Xiaohu Zhai, Peijin Shang, Rui Lin, Meina Zhao, Dongmei Hu, Ying Yin, Aidong Wen, Miaomiao Xi
Extract of Salvia miltiorrhiza and Dalbergia Odorifera (SM-DOO) has been traditionally used for the prevention and treatment of cardiovascular diseases. However, information regarding the pharmacodyamic material basis and potential mechanism remain unknown. Male Sprague-Dawley rats were divided into four groups: Sham, Model, Diltiazem and SM-DOO group, n=6. Rats were pretreated with homologous drugs for 7 days, then subjected to 30 min of ischemia followed by 180 min of reperfusion. Cardioprotection effects of SM-DOO on myocardial ischemia/reperfusion (MI/R) injury rats were examined by hemodynamic, infarct area, histopathology, biochemical indicators and western blot analysis...
January 16, 2017: Rejuvenation Research
https://www.readbyqxmd.com/read/28089566/metformin-inhibits-hepatic-mtorc1-signaling-via-dose-dependent-mechanisms-involving-ampk-and-the-tsc-complex
#4
Jessica J Howell, Kristina Hellberg, Marc Turner, George Talbott, Matthew J Kolar, Debbie S Ross, Gerta Hoxhaj, Alan Saghatelian, Reuben J Shaw, Brendan D Manning
Metformin is the most widely prescribed drug for the treatment of type 2 diabetes. However, knowledge of the full effects of metformin on biochemical pathways and processes in its primary target tissue, the liver, is limited. One established effect of metformin is to decrease cellular energy levels. The AMP-activated protein kinase (AMPK) and mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) are key regulators of metabolism that are respectively activated and inhibited in acute response to cellular energy depletion...
December 30, 2016: Cell Metabolism
https://www.readbyqxmd.com/read/28073046/olanzapine-and-aripiprazole-differentially-affect-glucose-uptake-and-energy-metabolism-in-human-mononuclear-blood-cells
#5
Britta Stapel, Alexandra Kotsiari, Michaela Scherr, Denise Hilfiker-Kleiner, Stefan Bleich, Helge Frieling, Kai G Kahl
The use of antipsychotics carries the risk of metabolic side effects, such as weight gain and new onset type-2 diabetes mellitus. The mechanisms of the observed metabolic alterations are not fully understood. We compared the effects of two atypical antipsychotics, one known to favor weight gain (olanzapine), the other not (aripiprazole), on glucose metabolism. Primary human peripheral blood mononuclear cells (PBMC) were isolated and stimulated with olanzapine or aripiprazole for 72 h. Cellular glucose uptake was analyzed in vitro by 18F-FDG uptake...
December 22, 2016: Journal of Psychiatric Research
https://www.readbyqxmd.com/read/28069379/ndrg2-overexpression-suppresses-hepatoma-cells-survival-during-metabolic-stress-through-disturbing-the-activation-of-fatty-acid-oxidation
#6
Tao Pan, Mei Zhang, Fang Zhang, Guang Yan, Yi Ru, Qinhao Wang, Yao Zhang, Xuehui Wei, Xinyuan Xu, Lan Shen, Jian Zhang, Kaichun Wu, Libo Yao, Xia Li
Because of the high nutrient consumption and inadequate vascularization, solid tumor constantly undergoes metabolic stress during tumor development. Oncogenes and tumor suppressor genes participated in cancer cells' metabolic reprogramming. N-Myc downstream regulated gene 2 (NDRG2) is a recently identified tumor suppressor gene, but its function in cancer metabolism, particularly during metabolic stress, remains unclear. In this study, we found that NDRG2 overexpression significantly reduced hepatoma cell proliferation and enhanced cell apoptosis under glucose limitation...
January 6, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28068143/adaptations-to-excess-choline-in-insulin-resistant-and-pcyt2-deficient-skeletal-muscle
#7
Adrian Taylor, Laila Cigana Schenkel, Maiya Yokich, Marica Bakovic
It was hypothesized that choline supplementation in insulin resistant (IR) CTP:phosphoethanolamine cytidylyltransferase deficient (Pcyt2(+/-)) mice would ameliorate muscle function by remodeling glucose and fatty acid (FA) metabolism. Pcyt2(+/-) mice either received no treatment or were allowed access to 2 mg/mL choline in drinking water for 4 weeks. Skeletal muscle was harvested from choline treated and untreated mice. Lipid analysis and metabolic gene expression and signaling pathways were compared between untreated Pcyt2(+/-) mice, treated Pcyt2(+/-) mice, and Pcyt2(+/+) mice...
September 6, 2016: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
https://www.readbyqxmd.com/read/28067405/lkb1-regulation-of-skeletal-muscle-development-metabolism-and-muscle-progenitor-cell-homeostasis
#8
REVIEW
Tizhong Shan, Ziye Xu, Jiaqi Liu, Weiche Wu, Yizhen Wang
Liver kinase B1 (Lkb1), also named as Serine/Threonine protein kinase 11 (STK11), is a serine/threonine kinase that plays crucial roles in various cellular processes including cell survival, cell division, cellular polarity, cell growth, cell differentiation, and cell metabolism. In metabolic tissues, Lkb1 regulates glucose homeostasis and energy metabolism through phosphorylating and activating the AMPK subfamily proteins. In skeletal muscle, Lkb1 affects muscle development and postnatal growth, lipid and fatty acid oxidation, glucose metabolism and insulin sensitivity...
January 9, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28062415/cardiomyocyte-specific-ablation-of-cd36-accelerates-the-progression-from-compensated-cardiac-hypertrophy-to-heart-failure
#9
Miranda M Sung, Nikole J Byrne, Ty T Kim, Jody Levasseur, Grant Masson, Jamie Boisvenue, Maria Febbraio, Jason R B Dyck
Previous studies have shown that loss of CD36 protects the heart from dysfunction induced by pressure overload in the presence of diet-induced insulin resistance and/or obesity. The beneficial effects of CD36 ablation in this context are mediated by preventing excessive cardiac fatty acid (FA) entry and reducing lipotoxic injury. However, whether or not the loss of CD36 can prevent pressure overload-induced cardiac dysfunction in the absence of chronic exposure to high circulating FAs is currently unknown. To address this, we utilized a tamoxifen inducible cardiomyocyte-specific CD36 knockout (icCD36KO) mouse and genetically deleted CD36 in adulthood...
January 6, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28057356/cell-wall-synthesis-and-central-carbohydrate-metabolism-are-interconnected-by-the-snf1-mig1-pathway-in-kluyveromyces-lactis
#10
Dorthe Rippert, Katja Backhaus, Rosaura Rodicio, Jürgen J Heinisch
The trimeric AMP-activated kinase complex (AMPK) is conserved from yeast to humans and is best known for its role in balancing energy metabolism. Additional functions, including the regulation of cell wall biosynthesis, have been proposed for the SNF1 complex, the baker's yeast homolog of AMPK. We here demonstrate that this function is conserved in the Crabtree-negative milk yeast Kluyveromyces lactis. Deletion mutants in the genes encoding the subunits of the trimeric complex (Klsnf1, Klgal83, Klsnf4) displayed increased sensitivities towards cell wall stress agents and a mutant lacking the kinase subunit had a thinner cell wall in transmission electron micrographs as compared to wild type...
December 28, 2016: European Journal of Cell Biology
https://www.readbyqxmd.com/read/28054981/the-root-extract-of-pueraria-lobata-and-its-main-compound-puerarin-prevent-obesity-by-increasing-the-energy-metabolism-in-skeletal-muscle
#11
Hyo Won Jung, An Na Kang, Seok Yong Kang, Yong-Ki Park, Mi Young Song
Radix Pueraria lobata (RP) has been reported to prevent obesity and improve glucose metabolism; however, the mechanism responsible for these effects has not been elucidated. The mechanism underlying anti-obesity effect of RP was investigated in high-fat diet (HFD) induced obese mice and skeletal muscle cells (C2C12). Five-week-old C5BL/6 mice were fed a HFD containing or not containing RP (100 or 300 mg/kg) or metformin (250 mg/kg) for 16 weeks. RP reduced body weight gain, lipid accumulation in liver, and adipocyte and blood lipid levels...
January 4, 2017: Nutrients
https://www.readbyqxmd.com/read/28042024/metformin-ameliorates-high-uric-acid-induced-insulin-resistance-in-skeletal-muscle-cells
#12
Huier Yuan, Yaqiu Hu, Yuzhang Zhu, Yongneng Zhang, Chaohuan Luo, Zhi Li, Tengfei Wen, Wanling Zhuang, Jinfang Zou, Liangli Hong, Xin Zhang, Ichiro Hisatome, Tetsuya Yamamoto, Jidong Cheng
Hyperuricemia occurs together with abnormal glucose metabolism and insulin resistance. Skeletal muscle is an important organ of glucose uptake, disposal, and storage. Metformin activates adenosine monophosphate-activated protein kinase (AMPK) to regulate insulin signaling and promote the translocation of glucose transporter type 4 (GLUT4), thereby stimulating glucose uptake to maintain energy balance. Our previous study showed that high uric acid (HUA) induced insulin resistance in skeletal muscle tissue. However, the mechanism of metformin ameliorating UA-induced insulin resistance in muscle cells is unknown and we aimed to determine it...
December 29, 2016: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28035400/ampk-activators-suppress-breast-cancer-cell-growth-by-inhibiting-dvl3-facilitated-wnt-%C3%AE-catenin-signaling-pathway-activity
#13
Yu-Feng Zou, Chun-Wei Xie, Shi-Xin Yang, Jian-Ping Xiong
Adenosine monophosphate-activated protein kinase (AMPK) is a principal regulator of metabolism and the conservation of energy in cells, and protects them from exposure to various stressors. AMPK activators may exhibit therapeutic potential as suppressors of cell growth; however, the molecular mechanism underlying this phenomenon in various cancer cells remains to be fully elucidated. The present study investigated the effects of AMPK activators on breast cancer cell growth and specified the underlying molecular mechanism...
February 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28034771/lkb1-promotes-metabolic-flexibility-in-response-to-energy-stress
#14
Seth J Parker, Robert U Svensson, Ajit S Divakaruni, Austin E Lefebvre, Anne N Murphy, Reuben J Shaw, Christian M Metallo
The Liver Kinase B1 (LKB1) tumor suppressor acts as a metabolic energy sensor to regulate AMP-activated protein kinase (AMPK) signaling and is commonly mutated in various cancers, including non-small cell lung cancer (NSCLC). Tumor cells deficient in LKB1 may be uniquely sensitized to metabolic stresses, which may offer a therapeutic window in oncology. To address this question we have explored how functional LKB1 impacts the metabolism of NSCLC cells using (13)C metabolic flux analysis. Isogenic NSCLC cells expressing functional LKB1 exhibited higher flux through oxidative mitochondrial pathways compared to those deficient in LKB1...
December 26, 2016: Metabolic Engineering
https://www.readbyqxmd.com/read/28008135/gfat1-phosphorylation-by-ampk-promotes-vegf-induced-angiogenesis
#15
Darya Zibrova, Franck Vandermoere, Olga Göransson, Mark Peggie, Karina V Mariño, Anne Knierim, Katrin Spengler, Cora Weigert, Benoit Viollet, Nicholas A Morrice, Kei Sakamoto, Regine Heller
Activation of AMP-activated protein kinase (AMPK) in endothelial cells regulates energy homeostasis, stress protection and angiogenesis, but the underlying mechanisms are incompletely understood. Using a label-free phosphoproteomic analysis, we identified glutamine:fructose-6-phosphate amidotransferase 1 (GFAT1) as an AMPK substrate. GFAT1 is the rate-limiting enzyme in the hexosamine biosynthesis pathway (HBP) and as such controls the modification of proteins by O-linked β-N-acetylglucosamine (O-GlcNAc). In the present study, we tested the hypothesis that AMPK controls O-GlcNAc levels and function of endothelial cells via GFAT1 phosphorylation using biochemical, pharmacological, genetic and in vitro angiogenesis approaches...
22, 2016: Biochemical Journal
https://www.readbyqxmd.com/read/27966786/fibroblast-growth-factor-21-fgf21-promotes-formation-of-aerobic-myofibers-via-the-fgf21-sirt1-ampk-pgc1%C3%AE-pathway
#16
X Y Liu, Y L Wang, L M Hou, Y Z Xiong, S H Zhao
Fibroblast growth factor 21(FGF21) is a pivotal regulator of energy metabolism, which is currently being assessed as a potential drug target for the treatment of insulin-resistant conditions. However, the cellular mechanisms by which FGF21 affects myogenesis remain unclear. In this study, we explored the function of FGF21 in myogenesis both in vitro and in vivo. Our experiments showed for the first time that FGF21 promotes myoblast differentiation and serves as a switch of molecular transformation from anaerobic myofibers to aerobic myofibers via the FGF21-SIRT1-AMPK-PGC1α axis...
December 14, 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27941940/kefir-peptides-prevent-high-fructose-corn-syrup-induced-non-alcoholic-fatty-liver-disease-in-a-murine-model-by-modulation-of-inflammation-and-the-jak2-signaling-pathway
#17
H L Chen, T C Tsai, Y C Tsai, J W Liao, C C Yen, C M Chen
OBJECTIVE: In recent years, people have changed their eating habits, and high-fructose-containing bubble tea has become very popular. High-fructose intake has been suggested to be a key factor that induces non-alcoholic fatty liver disease (NAFLD). Kefir, a fermented milk product composed of microbial symbionts, has demonstrated numerous biological activities, including antibacterial, antioxidant and immunostimulating effects. The present study aims to evaluate the effects of kefir peptides on high-fructose-induced hepatic steatosis and the possible molecular mechanism...
December 12, 2016: Nutrition & Diabetes
https://www.readbyqxmd.com/read/27934965/role-and-mechanism-of-the-ampk-pathway-in-waterborne-zn-exposure-influencing-the-hepatic-energy-metabolism-of-synechogobius-hasta
#18
Kun Wu, Chao Huang, Xi Shi, Feng Chen, Yi-Huan Xu, Ya-Xiong Pan, Zhi Luo, Xu Liu
Previous studies have investigated the physiological responses in the liver of Synechogobius hasta exposed to waterborne zinc (Zn). However, at present, very little is known about the underlying molecular mechanisms of these responses. In this study, RNA sequencing (RNA-seq) was performed to analyse the differences in the hepatic transcriptomes between control and Zn-exposed S. hasta. A total of 36,339 unigenes and 1,615 bp of unigene N50 were detected. These genes were further annotated to the Nonredundant protein (NR), Nonredundant nucleotide (Nt), Swiss-Prot, Kyoto Encyclopedia of Genes and Genomes (KEGG), Clusters of Orthologous Groups (COG) and Gene Ontology (GO) databases...
December 9, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27931848/human-peripheral-late-exhausted-memory-b-cells-express-a-senescent-associated-secretory-phenotype-and-preferentially-utilize-metabolic-signaling-pathways
#19
Daniela Frasca, Alain Diaz, Maria Romero, Bonnie B Blomberg
The percentage of late/exhausted memory (LM) B cells increases with age and we show here that this is associated with a lower influenza vaccine response. To identify novel contributors to the phenotypic and functional changes observed in aged B cells, we sorted the major peripheral B cell subsets [naïve, IgM memory, switched memory (swIg) and late/exhausted memory (LM)] and determined their percentages in the peripheral blood as well as their level of immune activation by measuring basal levels of expression of multiple senescence-associated secretory phenotype (SASP) markers, such as pro-inflammatory cytokines (TNF-α/IL-6/IL-8), inflammatory micro-RNAs (miRs, miR-155/16/93), cell cycle regulators (p16(INK4))...
January 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/27923067/chronological-lifespan-in-yeast-is-dependent-on-the-accumulation-of-storage-carbohydrates-mediated-by-yak1-mck1-and-rim15-kinases
#20
Lu Cao, Yingzhi Tang, Zhenzhen Quan, Zhe Zhang, Stephen G Oliver, Nianshu Zhang
Upon starvation for glucose or any other macronutrient, yeast cells exit from the mitotic cell cycle and acquire a set of characteristics that are specific to quiescent cells to ensure longevity. Little is known about the molecular determinants that orchestrate quiescence entry and lifespan extension. Using starvation-specific gene reporters, we screened a subset of the yeast deletion library representing the genes encoding 'signaling' proteins. Apart from the previously characterised Rim15, Mck1 and Yak1 kinases, the SNF1/AMPK complex, the cell wall integrity pathway and a number of cell cycle regulators were shown to be necessary for proper quiescence establishment and for extension of chronological lifespan (CLS), suggesting that entry into quiescence requires the integration of starvation signals transmitted via multiple signaling pathways...
December 2016: PLoS Genetics
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