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https://www.readbyqxmd.com/read/28230173/a-novel-physiological-role-for-cardiac-myoglobin-in-lipid-metabolism
#1
Ulrike B Hendgen-Cotta, Sonja Esfeld, Cristina Coman, Robert Ahrends, Ludger Klein-Hitpass, Ulrich Flögel, Tienush Rassaf, Matthias Totzeck
Continuous contractile activity of the heart is essential and the required energy is mostly provided by fatty acid (FA) oxidation. Myocardial lipid accumulation can lead to pathological responses, however the underlying mechanisms remain elusive. The role of myoglobin in dioxygen binding in cardiomyocytes and oxidative skeletal muscle has widely been appreciated. Our recent work established myoglobin as a protector of cardiac function in hypoxia and disease states. We here unravel a novel role of cardiac myoglobin in governing FA metabolism to ensure the physiological energy production through β-oxidation, preventing myocardial lipid accumulation and preserving cardiac functions...
February 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28218306/plin5-alleviates-myocardial-ischaemia-reperfusion-injury-by-reducing-oxidative-stress-through-inhibiting-the-lipolysis-of-lipid-droplets
#2
Pengfei Zheng, Zhonglin Xie, Yuan Yuan, Wen Sui, Chao Wang, Xing Gao, Yuanlin Zhao, Feng Zhang, Yu Gu, Peizhen Hu, Jing Ye, Xuyang Feng, Lijun Zhang
Myocardial ischaemia-reperfusion (I/R) injury is a complex pathophysiological process. Current research has suggested that energy metabolism disorders, of which the abnormal consumption of fatty acids is closely related, compose the main pathological basis for myocardial I/R injury. Lipid droplets (LD) are critical regulators of lipid metabolism by LD-associated proteins. Among the lipid droplet proteins, the perilipin family members regulate lipolysis and lipogenesis through different mechanisms. Plin5, an important perilipin protein, promotes LD generation and lowers fatty acid oxidation, thus protecting the myocardium from lipotoxicity...
February 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28215516/aisf-position-paper-on-nonalcoholic-fatty-liver-disease-nafld-updates-and-future-directions
#3
Amedeo Lonardo, Fabio Nascimbeni, Giovanni Targher, Mauro Bernardi, Ferruccio Bonino, Elisabetta Bugianesi, Alessandro Casini, Amalia Gastaldelli, Giulio Marchesini, Fabio Marra, Luca Miele, Filomena Morisco, Salvatore Petta, Fabio Piscaglia, Gianluca Svegliati-Baroni, Luca Valenti, Stefano Bellentani
This review summarizes our current understanding of nonalcoholic fatty liver disease (NAFLD), a multi-factorial systemic disease resulting from a complex interaction between a specific genetic background and multiple environmental/metabolic "hits". The role of gut microbiota, lipotoxicity, inflammation and their molecular pathways is reviewed in-depth. We also discuss the epidemiology and natural history of NAFLD by pinpointing the remarkably high prevalence of NAFLD worldwide and its inherent systemic complications: hepatic (steatohepatitis, advanced fibrosis and cirrhosis), cardio-metabolic (cardiovascular disease, cardiomyopathy, arrhythmias and type 2 diabetes) and neoplastic (primary liver cancers and extra-hepatic cancers)...
January 23, 2017: Digestive and Liver Disease
https://www.readbyqxmd.com/read/28214892/baicalin-attenuates-cardiac-dysfunction-and-myocardial-remodeling-in-a-chronic-pressure-overload-mice-model
#4
Yanqing Zhang, Pingping Liao, Meng'en Zhu, Wei Li, Dan Hu, Siming Guan, Long Chen
BACKGROUND/AIMS: Baicalin has been shown to be effective for various animal models of cardiovascular diseases, such as pulmonary hypertension, atherosclerosis and myocardial ischaemic injury. However, whether baicalin plays a role in cardiac hypertrophy remains unknown. Here we investigated the protective effects of baicalin on cardiac hypertrophy induced by pressure overload and explored the potential mechanisms involved. METHODS: C57BL/6J-mice were treated with baicalin or vehicle following transverse aortic constriction or Sham surgery for up to 8 weeks, and at different time points, cardiac function and heart size measurement and histological and biochemical examination were performed...
February 16, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28214337/palmitate-induces-mitochondrial-superoxide-generation-and-activates-ampk-in-podocytes
#5
Eugene Lee, Jin Choi, Hyun Soon Lee
Studies have shown that high levels of serum free fatty acids (FFAs) are associated with lipotoxicity and type 2 diabetes. Palmitic acid (PA) is the predominant circulating saturated FFA, yet its role in the pathogenesis of diabetic nephropathy (DN) is not clear. Recently, one study suggested that mitochondrial superoxide production is related to AMP-activated protein kinase (AMPK) activity in diabetic mice kidneys. To elucidate the link between PA and oxidative stress and AMPK activity in DN, we compared the cultured murine podocytes exposed to PA and oleic acid (OA)...
February 18, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28194887/atgl-deficiency-induces-podocyte-apoptosis-and-leads-to-glomerular-filtration-barrier-damage
#6
Wen Chen, Youzhao Jiang, Jian Han, Jiongyu Hu, Ting He, Tiantian Yan, Huang Na, Qiong Zhang, Hao Mei, Yong Liao, Yuesheng Huang, Bing Chen
Abnormal lipid metabolism, renal lipid accumulation and lipotoxicity are associated with the pathological features of glomerulopathy. However, the mechanisms by which lipid accumulation leads to the development or progression of this disease have not been fully elucidated. In this work, we have identified a role for the rate-limiting enzyme in lipolysis, adipose triglyceride lipase (ATGL; also called patatin-like phospholipase domain-containing protein 2(PNPLP2), in renal lipid metabolism and kidney disease...
February 14, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28194435/foxp3-drives-oxidative-phosphorylation-and-protection-from-lipotoxicity
#7
Duncan Howie, Stephen Paul Cobbold, Elizabeth Adams, Annemieke Ten Bokum, Andra Stefania Necula, Wei Zhang, Honglei Huang, David J Roberts, Benjamin Thomas, Svenja S Hester, David J Vaux, Alexander G Betz, Herman Waldmann
Tregs can adopt a catabolic metabolic program with increased capacity for fatty acid oxidation-fueled oxidative phosphorylation (OXPHOS). It is unclear why this form of metabolism is favored in Tregs and, more specifically, whether this program represents an adaptation to the environment and developmental cues or is "hardwired" by Foxp3. Here we show, using metabolic analysis and an unbiased mass spectroscopy-based proteomics approach, that Foxp3 is both necessary and sufficient to program Treg-increased respiratory capacity and Tregs' increased ability to utilize fatty acids to fuel oxidative phosphorylation...
February 9, 2017: JCI Insight
https://www.readbyqxmd.com/read/28190774/reducing-vegf-b-signaling-ameliorates-renal-lipotoxicity-and-protects-against-diabetic-kidney-disease
#8
Annelie Falkevall, Annika Mehlem, Isolde Palombo, Benjamin Heller Sahlgren, Lwaki Ebarasi, Liqun He, A Jimmy Ytterberg, Hannes Olauson, Jonas Axelsson, Birgitta Sundelin, Jaakko Patrakka, Pierre Scotney, Andrew Nash, Ulf Eriksson
Diabetic kidney disease (DKD) is the most common cause of severe renal disease, and few treatment options are available today that prevent the progressive loss of renal function. DKD is characterized by altered glomerular filtration and proteinuria. A common observation in DKD is the presence of renal steatosis, but the mechanism(s) underlying this observation and to what extent they contribute to disease progression are unknown. Vascular endothelial growth factor B (VEGF-B) controls muscle lipid accumulation through regulation of endothelial fatty acid transport...
February 1, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28184028/long-term-administration-of-tacrolimus-and-everolimus-prevents-high-cholesterol-high-fructose-induced-steatosis-in-c57bl-6j-mice-by-inhibiting-de-novo-lipogenesis
#9
Sharma Love, Malik A Mudasir, Subhash C Bhardwaj, Gurdarshan Singh, Sheikh A Tasduq
AIM: To investigate the effects of tacrolimus (TC) and everolimus (EV) on non-alcoholic steatohepatitis (NASH) induced by high fat, high cholesterol and fructose (fast food) diet in C57BL/6J mice. MATERIALS AND METHODS: C57BL/6J mice were divided into four groups (n=8). 1) Standard Chow (SC); 2) Fast food (FF) diet; 3) FF + Tacrolimus (TC, 1mg/kg) and; 4) FF + Everolimus (EV, 1mg/kg) and treated for 16 weeks. Serum and tissue samples were analyzed for evidence of inflammation, fibrosis, lipogenesis, and apoptosis...
February 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28181428/new-potential-targets-of-glucagon-like-peptide-1-receptor-agonists-in-pancreatic-%C3%AE-cells-and-hepatocytes
#10
Won Young Lee
It is well known that both insulin resistance and decreased insulin secretory capacity are important factors in the pathogenesis of type 2 diabetes mellitus (T2DM). In addition to genetic factors, obesity and lipotoxicity can increase the risk of T2DM. Glucagon-like peptide 1 (GLP-1) receptor agonists are novel antidiabetic drugs with multiple effects. They can stimulate glucose-dependent insulin secretion, inhibit postprandial glucagon release, delay gastric emptying, and induce pancreatic β-cell proliferation...
February 8, 2017: Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28166809/b-cells-interactions-in-lipid-immune-responses-implications-in-atherosclerotic-disease
#11
REVIEW
Laura C Echeverri Tirado, Lina M Yassin
Atherosclerosis is considered as an inflammatory and chronic disorder with an important immunologic component, which underlies the majority of cardiovascular diseases; condition that belongs to a group of noncommunicable diseases that to date and despite of prevention and treatment approaches, they remain as the main cause of death worldwide, with 17.5 million of deaths every year. The impact of lipids in human health and disease is taking center stage in research, due to lipotoxicity explained by elevated concentration of circulating lipids, in addition to altered adipose tissue metabolism, and aberrant intracellular signaling...
February 6, 2017: Lipids in Health and Disease
https://www.readbyqxmd.com/read/28165842/stagnation-of-autophagy-a-novel-mechanism-of-renal-lipotoxicity
#12
Yoshitsugu Takabatake, Takeshi Yamamoto, Yoshitaka Isaka
Excessive fat intake can lead to cellular injury and inflammation (termed lipotoxicity), but studies on lipid metabolism in the kidney have been scarce. We recently identified a novel mechanism of lipotoxicity in the kidney proximal tubules especially focusing on the effect of lipid overload on lysosomal function and autophagic activity. Lipid overload basically stimulates macroautophagy/autophagy for renovation of the plasma and organelle membranes, which plays an essential role in maintaining the integrity of proximal tubules...
February 6, 2017: Autophagy
https://www.readbyqxmd.com/read/28162008/clinical-implications-of-understanding-the-association-between-oxidative-stress-and-pediatric-nafld
#13
Jake P Mann, Massimiliano Raponi, Valerio Nobili
Oxidative stress is central to the pathogenesis of non-alcoholic steatohepatitis. The reactive oxygen species (ROS) that characterise oxidative stress are generated in several cellular sites and their production is influence by multi-organ interactions. Areas covered: Mitochondrial dysfunction is the main source of ROS in fatty liver and is closely related to endoplasmic reticulum stress. Both are caused by lipotoxicity and together these three factors form a cycle of progressive organelle damage, resulting in sterile inflammation and apoptosis...
February 6, 2017: Expert Review of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28154371/oxidative-stress-and-calcium-dysregulation-by-palmitate-in-type-2-diabetes
#14
REVIEW
Luong Dai Ly, Shanhua Xu, Seong-Kyung Choi, Chae-Myeong Ha, Themis Thoudam, Seung-Kuy Cha, Andreas Wiederkehr, Claes B Wollheim, In-Kyu Lee, Kyu-Sang Park
Free fatty acids (FFAs) are important substrates for mitochondrial oxidative metabolism and ATP synthesis but also cause serious stress to various tissues, contributing to the development of metabolic diseases. CD36 is a major mediator of cellular FFA uptake. Inside the cell, saturated FFAs are able to induce the production of cytosolic and mitochondrial reactive oxygen species (ROS), which can be prevented by co-exposure to unsaturated FFAs. There are close connections between oxidative stress and organellar Ca(2+) homeostasis...
February 3, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28142119/ginkgolide-a-ameliorates-non-alcoholic-fatty-liver-diseases-on-high-fat-diet-mice
#15
Hyeon-Soo Jeong, Kang-Hoon Kim, In-Seung Lee, Ji Young Park, Yumi Kim, Ki-Suk Kim, Hyeung-Jin Jang
Non-alcoholic fatty liver disease (NAFLD) is one of the most common diseases worldwide and has continuously increased. NAFLD refers to a spectrum of diseases ranging from fatty liver to steatohepatitis, cirrhosis, and even to hepatocyte carcinoma. Excessive fatty acid enters the cell and the mitochondria undergo stress and unremoved ROS can trigger a form of cell apoptosis known as 'lipoapoptosis'. NASH arises from damaged liver hepatocytes due to lipotoxicity. NASH not only involves lipid accumulation and apoptosis but also inflammation...
January 28, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28132808/store-operated-ca-2-entry-controls-induction-of-lipolysis-and-the-transcriptional-reprogramming-to-lipid-metabolism
#16
Mate Maus, Mario Cuk, Bindi Patel, Jayson Lian, Mireille Ouimet, Ulrike Kaufmann, Jun Yang, Rita Horvath, Hue-Tran Hornig-Do, Zofia M Chrzanowska-Lightowlers, Kathryn J Moore, Ana Maria Cuervo, Stefan Feske
Ca(2+) signals were reported to control lipid homeostasis, but the Ca(2+) channels and pathways involved are largely unknown. Store-operated Ca(2+) entry (SOCE) is a ubiquitous Ca(2+) influx pathway regulated by stromal interaction molecule 1 (STIM1), STIM2, and the Ca(2+) channel ORAI1. We show that SOCE-deficient mice accumulate pathological amounts of lipid droplets in the liver, heart, and skeletal muscle. Cells from patients with loss-of-function mutations in STIM1 or ORAI1 show a similar phenotype, suggesting a cell-intrinsic role for SOCE in the regulation of lipid metabolism...
January 21, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28128379/regulation-of-lipids-is-central-to-replicative-senescence
#17
Darleny Y Lizardo, Yen-Lung Lin, Omer Gokcumen, G Ekin Atilla-Gokcumen
Cellular replicative senescence, a state of permanent cell-cycle arrest, has been linked to organismal aging, tissue repair and tumorigenesis. In this study, we comparatively investigated the global lipid profiles and mRNA content of proliferating and senescent-state BJ fibroblasts. We found that both expression levels of lipid-regulating genes and the abundance of specific lipid families, are actively regulated. We further found that 19 specific polyunsaturated triacylglycerol species constituted the most prominent changes in lipid composition during replicative senescence...
January 27, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28119423/lipid-droplet-biogenesis-and-function-in-the-endothelium
#18
Andrew Kuo, Monica Y Lee, William C Sessa
RATIONALE: Fatty acids (FA) are transported across the capillary endothelium to parenchymal tissues. However, it is not known how endothelial cells (EC) process a post-prandial surge of FA. OBJECTIVE: This study was designed to characterize lipid droplet (LD) formation and function in EC. METHODS AND RESULTS: LD form and degrade in EC in vivo after FA loading. In cultured EC, LD synthesis and turnover is dynamic and function to protect EC from lipotoxic stress and provide FA for metabolic needs...
January 24, 2017: Circulation Research
https://www.readbyqxmd.com/read/28110829/lipidomic-analysis-reveals-significant-lipogenesis-and-accumulation-of-lipotoxic-components-in-ob-ob-mouse-organs
#19
Jun Hayakawa, Miao Wang, Chunyan Wang, Rowland H Han, Zhen Y Jiang, Xianlin Han
To further understand the role of lipogenesis and lipotoxicity in the development of obesity and diabetes, lipidomes of various organs from ob/ob mice and their wild type controls were analyzed by shotgun lipidomics at 10, 12, and 16 weeks of age. We observed that the amounts of fatty acyl (FA) chains corresponding to those from de novo synthesis (e.g., 16:0, 16:1, and 18:1 FA) were substantially elevated in ob/ob mice, consistent with increased expression of genes and proteins involved in biosynthesis. Polyunsaturated fatty acid species were moderately increased in the examined tissues of ob/ob mice, since they can only be absorbed from diets or elongated from the ingested n-3 or n-6 FA...
January 11, 2017: Prostaglandins, Leukotrienes, and Essential Fatty Acids
https://www.readbyqxmd.com/read/28107086/interaction-between-lipid-droplets-and-endoplasmic-reticulum-in-human-atherosclerotic-plaques
#20
Ida Perrotta
Lipid droplets (LDs) are intracellular organelles that are found in nearly all cell types, where they serve fundamental roles in lipid metabolism and energy homeostasis. Traditionally considered as simple lipid storage deposits, these dynamic and remarkable organelles have recently been implicated in a number of other cellular functions, ranging from protein storage and degradation to virus replication. Intracellular accumulation of LDs is also a hallmark feature of diverse human diseases including diabetes type II, obesity, hepatosteatosis, cancer, and atherosclerosis...
January 20, 2017: Ultrastructural Pathology
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