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https://www.readbyqxmd.com/read/28806138/lipid-droplets-and-lipotoxicity-during-autophagy
#1
Truc B Nguyen, James A Olzmann
Lipid droplets (LDs) are neutral lipid storage organelles that provide a rapidly accessible source of fatty acids (FAs) for energy during periods of nutrient deprivation. Surprisingly, lipids released by the macroautophagic/autophagic breakdown of membranous organelles are packaged and stored in new LDs during periods of prolonged starvation. Why cells would store FAs during an energy crisis was unknown. In our recent study, we demonstrated that FAs released during MTORC1-regulated autophagy are selectively channeled by DGAT1 (diacylglycerol O-acyltransferase 1) into triacylglycerol (TAG)-rich LDs...
August 14, 2017: Autophagy
https://www.readbyqxmd.com/read/28805685/re-adaption-on-earth-after-spaceflights-affects-the-mouse-liver-proteome
#2
Viktoria Anselm, Svetlana Novikova, Victor Zgoda
Harsh environmental conditions including microgravity and radiation during prolonged spaceflights are known to alter hepatic metabolism. Our studies have focused on the analysis of possible changes in metabolic pathways in the livers of mice from spaceflight project "Bion-M 1". Mice experienced 30 days of spaceflight with and without an additional re-adaption period of seven days compared to control mice on Earth. To investigate mice livers we have performed proteomic profiling utilizing shotgun mass spectrometry followed by label-free quantification...
August 12, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28798193/the-role-of-vascular-endothelial-growth-factor-b-in-metabolic-homeostasis-current-evidence
#3
Mohammad Ishraq Zafar, Juan Zheng, Wen Kong, Xiaofeng Ye, Luoning Gou, Anita Regmi, Lu-Lu Chen
It has been shown that adipose tissue and skeletal muscles of lean individuals respond to meal-induced hyperinsulinemia by increases in perfusion, the effect not observed in patients with metabolic syndrome. In conditions of hyperglycaemia and hypertriglyceridemia, this insufficient vascularization leads to the liberation of reactive oxygen species, and disruption of nitric oxide synthesis and endothelial signalling responsible for the uptake of circulating fatty acids, whose accumulation in skeletal muscles and adipose tissue is widely associated with impairment of insulin signalling...
August 10, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28792632/a-simple-and-economical-strategy-for-obtaining-calibration-plots-for-relative-quantification-of-positional-isomers-of-yyx-yxy-triglycerides-using-high-performance-liquid-chromatography-tandem-mass-spectrometry
#4
Elizabeth J Judge, Dong Zheng, Swathilekha Chivukula, Robert Gakwaya, Sarah Schostarez, Xingwen Li, Melissa Liriano, Jason J Evans
RATIONAL: Positional analysis of intact triglycerides could provide greater insights into the link between fatty acid position and lipotoxic diseases. However, this methodology has been impeded by lack of commercial availability of positionally pure triglycerides. This work reports on a strategy for defining calibration plots for YXY/YYX triglyceride systems based on the product ion intensities in the collisional-induced dissociation spectra of ammoniated parent ions. METHODS: A set of triglycerides were synthesized and analyzed by electrospray tandem mass spectrometry using an ion trap mass spectrometer...
August 9, 2017: Rapid Communications in Mass Spectrometry: RCM
https://www.readbyqxmd.com/read/28781146/the-impact-of-foxo-1-to-cardiac-pathology-in-diabetes-mellitus-and-diabetes-related-metabolic-abnormalities
#5
Dimitry A Chistiakov, Alexander N Orekhov, Yuri V Bobryshev
Diabetic heart pathology has a serious social impact due to high prevalence worldwide and significant mortality/invalidation of diabetic patients suffered from cardiomyopathy. The pathogenesis of diabetic and diabetes-related cardiomyopathy is associated with progressive loss and impairment of cardiac function due to adverse effects of metabolic, prooxidant, proinflammatory, and pro-apoptotic stress factors. In the adult heart, the transcriptional factor forkhead box-1 (FOXO-1) is involved in maintaining cardiomyocytes in the homeostatic state and induction of their adaptation to metabolic and pro-oxidant stress stimuli...
August 2, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28771229/autophagy-couteracts-weight-gain-lipotoxicity-and-pancreatic-%C3%AE-cell-death-upon-hypercaloric-pro-diabetic-regimens
#6
Álvaro F Fernández, Clea Bárcena, Gemma G Martínez-García, Isaac Tamargo-Gómez, María F Suárez, Federico Pietrocola, Francesca Castoldi, Lorena Esteban, Elena Sierra-Filardi, Patricia Boya, Carlos López-Otín, Guido Kroemer, Guillermo Mariño
In the last years, autophagy has been revealed as an essential pathway for multiple biological processes and physiological functions. As a catabolic route, autophagy regulation by nutrient availability has been evolutionarily conserved from yeast to mammals. On one hand, autophagy induction by starvation is associated with a significant loss in body weight in mice. Here, we demonstrate that both genetic and pharmacological inhibition of the autophagy process compromise weight loss induced by starvation. Moreover, autophagic potential also impacts on weight gain induced by distinct hypercaloric regimens...
August 3, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28768719/the-specialized-pro-resolving-lipid-mediator-maresin-1-protects-hepatocytes-from-lipotoxic-and-hypoxia-induced-endoplasmic-reticulum-stress
#7
Bibiana Rius, Marta Duran-Güell, Roger Flores-Costa, Cristina López-Vicario, Aritz Lopategi, José Alcaraz-Quiles, Mireia Casulleras, Juan José Lozano, Esther Titos, Joan Clària
Endoplasmic reticulum (ER) stress and activation of the unfolded protein response (UPR) are hallmarks of nonalcoholic fatty liver disease (NAFLD), which is the hepatic manifestation of the metabolic syndrome associated with obesity. The specialized pro-resolving lipid mediator maresin 1 (MaR1) preserves tissue homeostasis by exerting cytoprotective actions, dampening inflammation, and expediting its timely resolution. Here, we explored whether MaR1 protects liver cells from lipotoxic and hypoxia-induced ER stress...
August 2, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28768178/triglyceride-synthesis-by-dgat1-protects-adipocytes-from-lipid-induced-er-stress-during-lipolysis
#8
Chandramohan Chitraju, Niklas Mejhert, Joel T Haas, L Grisell Diaz-Ramirez, Carrie A Grueter, Jason E Imbriglio, Shirly Pinto, Suneil K Koliwad, Tobias C Walther, Robert V Farese
Triglyceride (TG) storage in adipose tissue provides the major reservoir for metabolic energy in mammals. During lipolysis, fatty acids (FAs) are hydrolyzed from adipocyte TG stores and transported to other tissues for fuel. For unclear reasons, a large portion of hydrolyzed FAs in adipocytes is re-esterified to TGs in a "futile," ATP-consuming, energy dissipating cycle. Here we show that FA re-esterification during adipocyte lipolysis is mediated by DGAT1, an ER-localized DGAT enzyme. Surprisingly, this re-esterification cycle does not preserve TG mass but instead functions to protect the ER from lipotoxic stress and related consequences, such as adipose tissue inflammation...
August 1, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28760262/corrigendum-to-disruption-of-calpain-reduces-lipotoxicity-induced-cardiac-injury-by-preventing-endoplasmic-reticulum-stress-biochim-biophy-acta-1862-11-2023-2033
#9
S Li, L Zhang, R Ni, T Cao, D Zheng, S Xiong, P A Greer, G C Fan, T Peng
No abstract text is available yet for this article.
September 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28753653/induction-of-sphk1-activity-in-obese-adipose-tissue-macrophages-promotes-survival
#10
Tanit L Gabriel, Mina Mirzaian, Berend Hooibrink, Roelof Ottenhoff, Cindy van Roomen, Johannes M F G Aerts, Marco van Eijk
During obesity, adipose tissue macrophages (ATM) are increased in concert with local inflammation and insulin resistance. Since the levels of sphingolipid (SLs) in adipose tissue (AT) are altered during obesity we investigated the potential impact of SLs on ATMs. For this, we first analyzed expression of SL metabolizing genes in ATMs isolated from obese mice. A marked induction of sphingosine kinase 1 (Sphk1) expression was observed in obese ATM when compared to lean ATM. This induction was observed in both MGL-ve (M1) and MGL1+ve (M2) macrophages from obese WAT...
2017: PloS One
https://www.readbyqxmd.com/read/28751022/er-resident-antioxidative-gpx7-and-gpx8-enzyme-isoforms-protect-insulin-secreting-ins-1e-%C3%AE-cells-against-lipotoxicity-by-improving-the-er-antioxidative-capacity
#11
Ilir Mehmeti, Stephan Lortz, Edward Avezov, Anne Jörns, Sigurd Lenzen
Increased circulating levels of saturated fatty acids (FFAs) and glucose are considered to be major mediators of β-cell dysfunction and death in T2DM. Although it has been proposed that endoplasmic reticulum (ER) and oxidative stress play a crucial role in gluco/lipotoxicity, their interplay and relative contribution to β-cell dysfunction and apoptosis has not been fully elucidated. In addition it is still unclear how palmitate - the physiologically most abundant long-chain saturated FFA - elicits ER stress and which immediate signals commit β-cells to apoptosis...
July 24, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28741157/eicosapentaenoic-acid-protects-cardiomyoblasts-from-lipotoxicity-in-an-autophagy-dependent-manner
#12
Hsiu-Ching Hsu, Sin-Jin Li, Ching-Yi Chen, Ming-Fong Chen
BACKGROUND AND AIMS: The cardiovascular health benefits of eicosapentaenoic acid (EPA) have been demonstrated previously; however, the exact mechanism underlying them remains unclear. Our previous study found that lipotoxicity induced cardiomyocyte apoptosis via the inhibition of autophagy. Accordingly, in this study, we investigated whether EPA attenuated lipotoxicity-induced cardiomyocyte apoptosis through autophagy regulation. The role of EPA in mitochondrial dynamics was analyzed as well...
July 24, 2017: Cell Biology and Toxicology
https://www.readbyqxmd.com/read/28737815/isofraxidin-a-coumarin-component-improves-high-fat-diet-induced-hepatic-lipid-homeostasis-disorder-and-macrophage-inflammation-in-mice
#13
Jian Li, Xiaofei Li, Zhike Li, Lu Zhang, Yonggang Liu, Hong Ding, Shanye Yin
Isofraxidin (IF) is a coumarin compound produced in the functional foods Siberian ginseng and Apium graveolens. The first objective of this study was to investigate the protective effects and putative methods of IF in combating lipotoxicity in vitro and in vivo. Oleic acid was used to induce lipid turbulence in human hepatoma cells (HepG2). Alterations in triglyceride metabolism, inflammation and oxidative status were monitored. Results show that IF mainly reduced triglyceride accumulation, TNF-α release and ROS activation in metabolic disordered cells...
August 1, 2017: Food & Function
https://www.readbyqxmd.com/read/28724742/the-myokine-irisin-is-released-in-response-to-saturated-fatty-acids-and-promotes-pancreatic-beta-cell-survival-and-insulin-secretion
#14
Annalisa Natalicchio, Nicola Marrano, Giuseppina Biondi, Rosaria Spagnuolo, Rossella Labarbuta, Immacolata Porreca, Angelo Cignarelli, Marco Bugliani, Piero Marchetti, Sebastio Perrini, Luigi Laviola, Francesco Giorgino
This study explored the role of irisin as a new pancreatic beta-cell secretagogue and survival factor and its potential role in the communication between skeletal muscle and pancreatic beta-cells under lipotoxic conditions. Recombinant irisin stimulated insulin biosynthesis and glucose-stimulated insulin secretion (GSIS) in a PKA-dependent manner, and prevented saturated fatty acid-induced apoptosis in human and rat pancreatic beta-cells, as well as in human and murine pancreatic islets, via AKT/BCL2 signaling...
July 19, 2017: Diabetes
https://www.readbyqxmd.com/read/28719397/obesity-and-pancreatitis
#15
Biswajit Khatua, Bara El-Kurdi, Vijay P Singh
PURPOSE OF REVIEW: The obesity pandemic poses a unique set of problems for acute pancreatitis - both by increasing acute pancreatitis incidence, and worsening acute pancreatitis severity. This review explores these associations, underlying mechanisms, and potential therapies. RECENT FINDINGS: We review how the obesity associated increase in gallstones, surgical, and endoscopic interventions for obesity management, diabetes, and related medications such as incretin-based therapies and hypertriglyceridemia may increase the incidence of acute pancreatitis...
September 2017: Current Opinion in Gastroenterology
https://www.readbyqxmd.com/read/28715446/active-subfractions-of-abelmoschus-esculentus-substantially-prevent-free-fatty-acid-induced-%C3%AE-cell-apoptosis-via-inhibiting-dipeptidyl-peptidase-4
#16
Chien-Ning Huang, Chau-Jong Wang, Yi-Ju Lee, Chiung-Huei Peng
Lipotoxicity plays an important role in exacerbating type 2 diabetes mellitus (T2DM) and leads to apoptosis of β cells. Recently dipeptidyl peptidase-4 (DPP-4) inhibitors have emerged as a useful tool in the treatment of T2DM. DPP-4 degrades type 1 glucagon-like peptide (GLP-1), and GLP-1 receptor (GLP-1R) signaling has been shown to protect β cells by modulating AMPK/mTOR, PI3K, and Bax. The anti-hyperglycemic effect of Abelmoschus esculentus (AE) is well known, however its mucilage makes it difficult to further examine this effect...
2017: PloS One
https://www.readbyqxmd.com/read/28698383/pancreatic-%C3%AE-cell-protection-from-inflammatory-stress-by-the-endoplasmic-reticulum-proteins-thrombospondin-1-and-mesencephalic-astrocyte-derived-neutrotrophic-factor-manf
#17
Daniel A Cunha, Monia Cito, Fabio A Grieco, Cristina Cosentino, Tatiana Danilova, Laurence Ladriere, Maria Lindahl, Andrii Domanskyi, Marco Bugliani, Piero Marchetti, Decio L Eizirik, Miriam Cnop
Cytokine-induced endoplasmic reticulum (ER) stress is one of the molecular mechanisms underlying pancreatic β-cell demise in type 1 diabetes. Thrombospondin-1 (THBS1) was recently shown to promote β-cell survival during lipotoxic stress. Here we show that ER-localized THBS1 is cytoprotective to rat, mouse and human β-cells exposed to cytokines or thapsigargin-induced ER stress. THBS1 confers cytoprotection by maintaining expression of mesencephalic astrocyte-derived neutrotrophic factor (MANF) in β-cells, and thereby prevents the BH3-only protein BIM-dependent triggering of the mitochondrial pathway of apoptosis...
July 11, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28697336/dgat1-dependent-lipid-droplet-biogenesis-protects-mitochondrial-function-during-starvation-induced-autophagy
#18
Truc B Nguyen, Sharon M Louie, Joseph R Daniele, Quan Tran, Andrew Dillin, Roberto Zoncu, Daniel K Nomura, James A Olzmann
Lipid droplets (LDs) provide an "on-demand" source of fatty acids (FAs) that can be mobilized in response to fluctuations in nutrient abundance. Surprisingly, the amount of LDs increases during prolonged periods of nutrient deprivation. Why cells store FAs in LDs during an energy crisis is unknown. Our data demonstrate that mTORC1-regulated autophagy is necessary and sufficient for starvation-induced LD biogenesis. The ER-resident diacylglycerol acyltransferase 1 (DGAT1) selectively channels autophagy-liberated FAs into new, clustered LDs that are in close proximity to mitochondria and are lipolytically degraded...
July 10, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28694473/5-lo-inhibition-ameliorates-palmitic-acid-induced-er-stress-oxidative-stress-and-insulin-resistance-via-ampk-activation-in-murine-myotubes
#19
Hyun Jeong Kwak, Hye-Eun Choi, Hyae Gyeong Cheon
Leukotriene B4 (LTB4) production via the 5-lipoxygenase (5-LO) pathway contributes to the development of insulin resistance in adipose and hepatic tissues, but the role of LTB4 in skeletal muscle is relatively unknown. Here, the authors investigated the role of LTB4 in C2C12 myotubes in palmitic acid (PA)-induced ER stress, inflammation and insulin resistance. PA (750 μM) evoked lipotoxicity (ER stress, oxidative stress, inflammation and insulin resistance) in association with LTB4 production. 5-LO inhibition reduced all the lipotoxic effects induced by PA...
July 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28693962/the-impact-of-triglycerides-on-glucose-tolerance-lipotoxicity-revisited
#20
REVIEW
M Seghieri, D Tricò, A Natali
Elevated plasma triglycerides (TGs) are early key features of conditions associated with a dysregulation in glucose metabolism and may predict the development of type 2 diabetes (T2D) over time. Although the acute ingestion of lipid, either mixed with or shortly before the meal, is neutral or slightly beneficial on glucose tolerance, a short-term increase in plasma TGs induced by either an i.v. lipid infusion or a high-fat diet produces a deterioration of glucose control. Accordingly, chronic lowering of plasma TGs by fibrates improves glucose homeostasis and may also prevent T2D...
July 7, 2017: Diabetes & Metabolism
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