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https://www.readbyqxmd.com/read/29155055/cell-culture-models-of-fatty-acid-overload-problems-and-solutions
#1
REVIEW
Nour Alsabeeh, Bruno Chausse, Pamela A Kakimoto, Alicia J Kowaltowski, Orian Shirihai
High plasma levels of fatty acids occur in a variety of metabolic diseases. Cellular effects of fatty acid overload resulting in negative cellular responses (lipotoxicity) are often studied in vitro, in an attempt to understand mechanisms involved in these diseases. Fatty acids are poorly soluble, and thus usually studied when complexed to albumins such as bovine serum albumin (BSA). The conjugation of fatty acids to albumin requires care pertaining to preparation of the solutions, effective free fatty acid concentrations, use of different fatty acid species, types of BSA, appropriate controls and ensuring cellular fatty acid uptake...
November 15, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29154964/lipotoxicity-and-the-gut-liver-axis-in-nash-pathogenesis
#2
REVIEW
Fabio Marra, Gianluca Svegliati-Baroni
The pathogenesis of nanoalcoholic fatty liver disease is still incompletely understood, in particolar the mechanisms whereby a minority of patients develop a more severe phenotype characterized by hepatocellular damage, inflammation, and fibrosis. In this review we discuss two pivotal aspects of the pathogenesis of NASH. We first analyze the initial mechanisms responsible of hepatocellular damage and inflammation, which derive from the toxic effects of excess lipids. Accumulating data indicate that the total amount of triglycerides stored in hepatocytes is not the major determinant of lipotoxicity, and that specific lipid classes act as damaging agents on liver cells...
November 14, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/29136776/dihydroartemisinin-inhibits-er-stress-mediated-mitochondrial-pathway-to-attenuate-hepatocyte-lipoapoptosis-via-blocking-the-activation-of-the-pi3k-akt-pathway
#3
Xingran Chen, Mianli Bian, Chenxi Zhang, Jun Kai, Zhen Yao, Huanhuan Jin, Chunfeng Lu, Jiangjuan Shao, Anping Chen, Feng Zhang, Shizhong Zheng
Alcoholic liver disease (ALD), characterized by accumulation of fatty acids in liver cells, is usually caused by Chronic alcohol consumption. Our previous study has identified that DA protects against alcoholic liver injury in alcohol-fed rats through alleviating hepatocyte steatosis. It has emerged that saturated fatty acids could provoke endoplasmic reticulum (ER) stress and apoptosis in hepatocytes. This study was aimed to explore the impact of DA on ALD and further elaborate the underlying mechanisms. Results demonstrated that DA attenuates alcoholic liver injury in mice...
November 7, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29135069/impaired-secretion-of-active-glp-1-in-patients-with-hypertriglyceridaemia-a-novel-lipotoxicity-paradigm
#4
Xiangxiang Wang, Jia Liu, Chaolin Li, Meng Zhao, Lu Liu, Qingbo Guan, Haiqing Zhang, Xu Zhang, Ling Gao, Jiajun Zhao, Yongfeng Song
AIM: Lipotoxicity plays an important role in the pathogenesis of β-cell dysfunction. Glucagon-like peptide-1 (GLP-1) is an incretin hormone that exerts beneficial effects on the number and function of islet β cells. However, the effect of lipotoxicity on GLP-1 secretion is still unknown. METHODS: Twenty-five patients who were newly diagnosed with diabetes were recruited from 400 subjects based on 75 g Oral Glucose Tolerance Test (OGTT). Patients were divided into diabetes (DM) and DM combined with hypertriglyceridaemia (DM+HTG) groups according to their serum triglyceride (TG) levels...
November 14, 2017: Diabetes/metabolism Research and Reviews
https://www.readbyqxmd.com/read/29130531/acute-hypoxic-preconditioning-prevents-palmitic-acid-induced-cardiomyocyte-apoptosis-via-switching-metabolic-glut4-glucose-pathway-back-to-cd36-fatty-acid-dependent
#5
Yeh-Peng Chen, Wei-Wen Kuo, Rathinasamy Baskaran, Cecilia-Hsuan Day, Ray-Jade Chen, Su-Ying Wen, Tsung-Jung Ho, Viswanadha Vijaya Padma, Chia-Hua Kuo, Chih-Yang Huang
Metabolic syndrome is a risk factor for the development of cardiovascular diseases. Myocardial cell damage leads to an imbalance of energy metabolism, and many studies have indicated that short-term hypoxia during myocardial cell injury has a protective effect. In our previous animal studies, we found that short-term hypoxia in the heart has a protective effect, but long-term hypoxia increases myocardial cell injury. Palmitic acid (PA)-treated H9c2 cardiomyoblasts and neonatal rat ventricle cardiomyocytes were used to simulate hyperlipidemia model, which suppress cluster of differentiation 36 (CD36) and activate glucose transporter type 4 (GLUT4)...
November 11, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29127192/lipotoxic-very-long-chain-ceramides-cause-mitochondrial-dysfunction-oxidative-stress-and-cell-death-in-cardiomyocytes
#6
Brittany A Law, Xianghai Liao, Kelsey S Moore, Abigail Southard, Patrick Roddy, Ruiping Ji, Zdzislaw Sculz, Ala Bielawska, P Christian Schulze, L Ashley Cowart
Accumulating data support a role for bioactive lipids as mediators of lipotixicity in cardiomyocytes. One class of these, the ceramides, constitutes a family of molecules that differ in structure and are synthesized by distinct enzymes, ceramide synthase (CerS)1-CerS6. Data support that specific ceramides and the enzymes that catalyze their formation play distinct roles in cell function. In a mouse model of diabetic cardiomyopathy, sphingolipid profiling revealed increases in not only the CerS5-derived ceramides but also in very long chain (VLC) ceramides derived from CerS2...
November 10, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29121068/metabolic-regulation-of-glp-1-and-pc1-3-in-pancreatic-%C3%AE-cell-line
#7
Veronica Sancho, Giuseppe Daniele, Daniela Lucchesi, Roberto Lupi, Annamaria Ciccarone, Giuseppe Penno, Cristina Bianchi, Angela Dardano, Roberto Miccoli, Stefano Del Prato
BACKGROUND AND AIMS: An intra-islet incretin system has been recently suggested to operate through modulation of the expression and activity of proconvertase 1/3 and 2 (PC1/3, PC2) in pancreatic alpha-cell accounting for local release of GLP-1. Little is known, whether this alpha-cell activity can be affected by the metabolic alterations occurring in type 2 diabetes, such as hyperglycemia, hyperlipidemia or hyperglucagonemia. MATERIALS AND METHODS: AlphaTC1/6 cells from a mice pancreatic cell line were incubated in the presence of two glucose (G) concentration (5...
2017: PloS One
https://www.readbyqxmd.com/read/29119002/mechanisms-of-liver-disease-in-patients-infected-with-hiv
#8
REVIEW
Matthew B Kaspar, Richard K Sterling
Objective: To describe the various mechanisms of liver disease in patients with HIV infection, and to link these mechanisms to disease states which may utilise them. Background: Non-AIDS causes of morbidity and mortality are becoming increasingly common in patients chronically infected with HIV. In particular, liver-related diseases have risen to become one of the leading causes of non-AIDS-related death. A thorough understanding of the mechanisms driving the development of liver disease in these patients is essential when evaluating and caring for these patients...
2017: BMJ Open Gastroenterology
https://www.readbyqxmd.com/read/29114203/collagen-vi-null-mice-as-a-model-for-early-onset-muscle-decline-in-aging
#9
Daniele Capitanio, Manuela Moriggi, Sara De Palma, Dario Bizzotto, Sibilla Molon, Enrica Torretta, Chiara Fania, Paolo Bonaldo, Cecilia Gelfi, Paola Braghetta
Collagen VI is an extracellular matrix (ECM) protein playing a key role in skeletal muscles and whose deficiency leads to connective tissue diseases in humans and in animal models. However, most studies have been focused on skeletal muscle features. We performed an extensive proteomic profiling in two skeletal muscles (diaphragm and gastrocnemius) of wild-type and collagen VI null (Col6a1(-/-)) mice at different ages, from 6- (adult) to 12- (aged) month-old to 24 (old) month-old. While in wild-type animals the number of proteins and the level of modification occurring during aging were comparable in the two analyzed muscles, Col6a1(-/-) mice displayed a number of muscle-type specific variations...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29114202/estradiol-uses-different-mechanisms-in-astrocytes-from-the-hippocampus-of-male-and-female-rats-to-protect-against-damage-induced-by-palmitic-acid
#10
Laura M Frago, Sandra Canelles, Alejandra Freire-Regatillo, Pilar Argente-Arizón, Vicente Barrios, Jesús Argente, Luis M Garcia-Segura, Julie A Chowen
An excess of saturated fatty acids can be toxic for tissues, including the brain, and this has been associated with the progression of neurodegenerative diseases. Since palmitic acid (PA) is a free fatty acid that is abundant in the diet and circulation and can be harmful, we have investigated the effects of this fatty acid on lipotoxicity in hippocampal astrocytes and the mechanism involved. Moreover, as males and females have different susceptibilities to some neurodegenerative diseases, we accessed the responses of astrocytes from both sexes, as well as the possible involvement of estrogens in the protection against fatty acid toxicity...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29092894/mitochondrial-reactive-oxygen-species-in-lipotoxic-hearts-induces-post-translational-modifications-of-akap121-drp1-and-opa1-that-promote-mitochondrial-fission
#11
Kensuke Tsushima, Heiko Bugger, Adam R Wende, Jamie Soto, Gregory A Jenson, Austin R Tor, Rose McGlauflin, Helena C Kenny, Yuan Zhang, Rhonda Souvenir, Xiao X Hu, Crystal L Black, Renata O Pereira, Vitor A Lira, Kenneth Spitzer, Terry L Sharp, Kooresh I Shoghi, Genevieve C Sparagna, Eva A Rog-Zielinska, Peter Kohl, Oleh Khalimonchuk, Jean E Schaffer, E Dale Abel
Rationale: Cardiac lipotoxicity, characterized by increased uptake, oxidation and accumulation of lipid intermediates, contributes to cardiac dysfunction in obesity and diabetes. However, mechanisms linking lipid overload and mitochondrial dysfunction are incompletely understood. Objective: To elucidate the mechanisms for mitochondrial adaptations to lipid overload in postnatal hearts in vivo. Methods and Results: Using a transgenic mouse model of cardiac lipotoxicity overexpressing long-chain acyl-CoA synthetase 1 in cardiomyocytes, we show that modestly increased myocardial fatty acid uptake leads to mitochondrial structural remodeling with significant reduction in minimum diameter...
November 1, 2017: Circulation Research
https://www.readbyqxmd.com/read/29081381/inflammageing-and-metaflammation-the-yin-and-yang-of-type-2-diabetes
#12
REVIEW
Francesco Prattichizzo, Valeria De Nigris, Rosangela Spiga, Elettra Mancuso, Lucia La Sala, Roberto Antonicelli, Roberto Testa, Antonio Domenico Procopio, Fabiola Olivieri, Antonio Ceriello
Type 2 diabetes mellitus (T2DM) is characterised by chronic low-grade inflammation, recently referred to as 'metaflammation', a relevant factor contributing to the development of both diabetes and its complications. Nonetheless, 'canonical' anti-inflammatory drugs do not yield satisfactory results in terms of prevention of diabetes progression and of cardiovascular events, suggesting that the causal mechanisms fostering metaflammation deserve further research to identify new druggable targets. Metaflammation resembles ageing-induced low-grade inflammation, previously referred to as inflammageing, in terms of clinical presentation and the molecular profile, pointing to a common aetiology for both conditions...
October 31, 2017: Ageing Research Reviews
https://www.readbyqxmd.com/read/29075199/brain-ceramide-metabolism-in-the-control-of-energy-balance
#13
REVIEW
Céline Cruciani-Guglielmacci, Miguel López, Mélanie Campana, Hervé le Stunff
The regulation of energy balance by the central nervous system (CNS) is a key actor of energy homeostasis in mammals, and deregulations of the fine mechanisms of nutrient sensing in the brain could lead to several metabolic diseases such as obesity and type 2 diabetes (T2D). Indeed, while neuronal activity primarily relies on glucose (lactate, pyruvate), the brain expresses at high level enzymes responsible for the transport, utilization and storage of lipids. It has been demonstrated that discrete neuronal networks in the hypothalamus have the ability to detect variation of circulating long chain fatty acids (FA) to regulate food intake and peripheral glucose metabolism...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/29070903/increasing-dietary-medium-chain-fatty-acid-ratio-mitigates-high-fat-diet-induced-non-alcoholic-steatohepatitis-by-regulating-autophagy
#14
Mu-En Wang, Brijesh K Singh, Meng-Chieh Hsu, Chien Huang, Paul M Yen, Leang-Shin Wu, De-Shien Jong, Chih-Hsien Chiu
Previous studies have demonstrated that saturated fatty acids (SFAs) are more lipotoxic than unsaturated fatty acids (UFAs) in inhibiting hepatic autophagy and promoting non-alcoholic steatohepatitis (NASH). However, there have been few studies have investigated the effects of carbon chain length on SFA-induced autophagy impairment and lipotoxicity. To investigate whether SFAs with shorter carbon chain lengths have differential effects on hepatic autophagy and NASH development, we partially replaced lard with coconut oil to elevate the ratio of medium-chain fatty acids (MCFAs) to long-chain fatty acids (LCFAs) in a mouse high-fat diet (HFD) and fed mice for 16 weeks...
October 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29070436/western-diet-increases-cardiac-ceramide-content-in-healthy-and-hypertrophied-hearts
#15
T J Butler, D Ashford, A-M Seymour
BACKGROUND AND AIMS: Obesity and cardiac left ventricular hypertrophy (LVH) are recognised independent risk factors in the development of heart failure (HF). However, the combination of these factors may exacerbate the onset of cardiovascular disease by mechanisms as yet unclear. LVH leads to significant cellular remodelling, including alterations in metabolism which may result in an inappropriate accumulation of lipids and eventual lipotoxicity and apoptosis. The aim of the study was to determine the impact of dietary manipulation on cardiac metabolism in the obese and hypertrophied heart...
September 7, 2017: Nutrition, Metabolism, and Cardiovascular Diseases: NMCD
https://www.readbyqxmd.com/read/29065430/lipidomic-changes-in-skeletal-muscle-in-patients-after-biliopancreatic-diversion
#16
Carola Sabine Mehnert, Juergen Graessler, Virginia Kamvissi-Lorenz, Lidia Castagneto Gissey, James R Casella Mariolo, Giovanni Casella, Geltrude Mingrone, Stefan R Bornstein
The mechanisms behind the fast improvements of insulin sensitivity and release of the diabetic metabolic state after bariatric surgery are still not completely understood. To further elucidate the effects on the individual cellular level, we applied mass spectrometry to investigate the changes in the lipidomic profile of skeletal muscle cells before and after biliopancreatic diversion in six patients. We found a decrease in lipid storage species, mainly triacylglycerides (e. g., TAG 52:2 from 19.84 to 13...
November 2017: Hormone and Metabolic Research, Hormon- und Stoffwechselforschung, Hormones et Métabolisme
https://www.readbyqxmd.com/read/29064461/endocrine-disruptors-leading-to-obesity-and-related-diseases
#17
REVIEW
Demetrios Petrakis, Loukia Vassilopoulou, Charalampos Mamoulakis, Christos Psycharakis, Aliki Anifantaki, Stavros Sifakis, Anca Oana Docea, John Tsiaoussis, Antonios Makrigiannakis, Aristides M Tsatsakis
The review aims to comprehensively present the impact of exposure to endocrine disruptors (EDs) in relation to the clinical manifestation of obesity and related diseases, including diabetes mellitus, metabolic syndrome, cardiovascular diseases, carcinogenesis and infertility. EDs are strong participants in the obesity epidemic scenery by interfering with cellular morphological and biochemical processes; by inducing inflammatory responses; and by presenting transcriptional and oncogenic activity. Obesity and lipotoxicity enhancement occur through reprogramming and/or remodeling of germline epigenome by exposure to EDs...
October 24, 2017: International Journal of Environmental Research and Public Health
https://www.readbyqxmd.com/read/29058819/involvement-of-dying-beta-cell-originated-messenger-molecules-in-differentiation-of-pancreatic-mesenchymal-stem-cells-under-glucotoxic-and-glucolipotoxic-conditions
#18
Selda Gezginci-Oktayoglu, Evren Onay-Ucar, Serap Sancar-Bas, Ayse Karatug-Kacar, Emine Sekure Nazli Arda, Sehnaz Bolkent
Beta cell mass regulation represents a critical issue for understanding and treatment of diabetes. The most important process in the development of diabetes is beta cell death, generally induced by glucotoxicity or glucolipotoxicity, and the regeneration mechanism of new beta cells that will replace dead beta cells is still not fully understood. The aim of this study was to investigate the generation mechanism of new beta cells by considering the compensation phase of type2 diabetes mellitus. Pancreatic islet derived mesenchymal stem cells (PI-MSCs) were isolated from adult rats and characterized...
October 23, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29055392/sleep-apnea-an-overlooked-cause-of-lipotoxicity
#19
Chenjuan Gu, Haris Younas, Jonathan C Jun
Obstructive sleep apnea (OSA) is a common sleep disorder associated with diabetes and cardiovascular disease. However, the mechanisms by which OSA causes cardiometabolic dysfunction are not fully elucidated. OSA increases plasma free fatty acids (FFA) during sleep, reflecting excessive adipose tissue lipolysis. In animal studies, intermittent hypoxia simulating OSA also increases FFA, and the increase is attenuated by beta-adrenergic blockade. In other contexts, excessive plasma FFA can lead to ectopic fat accumulation, insulin resistance, vascular dysfunction, and dyslipidemia...
October 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/29044173/palmitate-induced-lipotoxicity-alters-acetylation-of-multiple-proteins-in-clonal-%C3%AE-cells-and-human-pancreatic-islets
#20
Federica Ciregia, Marco Bugliani, Maurizio Ronci, Laura Giusti, Claudia Boldrini, Maria R Mazzoni, Sandra Mossuto, Francesca Grano, Miriam Cnop, Lorella Marselli, Gino Giannaccini, Andrea Urbani, Antonio Lucacchini, Piero Marchetti
Type 2 diabetes is characterized by progressive β cell dysfunction, with lipotoxicity playing a possible pathogenetic role. Palmitate is often used to examine the direct effects of lipotoxicity and it may cause mitochondrial alterations by activating protein acetylation. However, it is unknown whether palmitate influences protein acetylation in β cells. We investigated lysine acetylation in mitochondrial proteins from INS-1E β cells (INS-1E) and in proteins from human pancreatic islets (HPI) after 24 h palmitate exposure...
October 18, 2017: Scientific Reports
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