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https://www.readbyqxmd.com/read/28214558/small-heterodimer-partner-shp-contributes-to-insulin-resistance-in-cardiomyocytes
#1
Ricardo Rodríguez-Calvo, Dipanjan Chanda, Yvonne Oligschlaeger, Marie Miglianico, Will A Coumans, Emma Barroso, Marta Tajes, Joost Jfp Luiken, Jan Fc Glatz, Manuel Vázquez-Carrera, Dietbert Neumann
Small heterodimer partner (SHP) is an atypical nuclear receptor expressed in heart that has been shown to inhibit the hypertrophic response. Here, we assessed the role of SHP in cardiac metabolism and inflammation. Mice fed a high-fat diet (HFD) displayed glucose intolerance accompanied by increased cardiac mRNA levels of Shp. In HL-1 cardiomyocytes, SHP overexpression inhibited both basal and insulin-stimulated glucose uptake and impaired the insulin signalling pathway (evidenced by reduced AKT and AS160 phosphorylation), similar to insulin resistant cells generated by high palmitate/high insulin treatment (HP/HI; 500μM/100nM)...
February 15, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28214337/palmitate-induces-mitochondrial-superoxide-generation-and-activates-ampk-in-podocytes
#2
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/28212523/redox-regulation-in-metabolic-programming-and-inflammation
#3
REVIEW
Helen R Griffiths, Dan Gao, Chathyan Pararasa
Energy metabolism and redox state are intrinsically linked. In order to mount an adequate immune response, cells must have an adequate and rapidly available energy resource to migrate to the inflammatory site, to generate reactive oxygen species using NADPH as a cofactor and to engulf bacteria or damaged tissue. The first responder cells of the innate immune response, neutrophils, are largely dependent on glycolysis. Neutrophils are relatively short-lived, dying via apoptosis in the process of bacterial killing through production of hypochlorous acid and release of extracellular NETs...
February 12, 2017: Redox Biology
https://www.readbyqxmd.com/read/28205579/tim-3-inhibits-macrophage-control-of-listeria-monocytogenes-by-inhibiting-nrf2
#4
Zhiding Wang, Dejun Sun, Guojiang Chen, Ge Li, Shuaijie Dou, Renxi Wang, He Xiao, Chunmei Hou, Yan Li, Jiannan Feng, Beifen Shen, Gencheng Han
T cell immunoglobulin mucin-3 (Tim-3) is an immune checkpoint inhibitor and its dysregulation has been related to T cell tolerance and many immune disorders, such as tumors and infection tolerance. However, the physiopathology roles of Tim-3 in innate immunity remain elusive. Here, we demonstrate that Tim-3 inhibits macrophage phagocytosis of L. monocytogenes by inhibiting the nuclear erythroid 2-related factor 2 (Nrf2) signaling pathway and increases bacterial burden. Tim-3 signaling promotes Nrf2 degradation by increasing its ubiquitination and, as a result, decreasing its nuclear translocation...
February 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28205069/transcriptomic-analysis-of-thp-1-macrophages-exposed-to-lipoprotein-hydrolysis-products-generated-by-lipoprotein-lipase
#5
Narmadaa Thyagarajan, Jenika D Marshall, Arthur T Pickett, Clemens Schumacher, Yanbo Yang, Sherri L Christian, Robert J Brown
Macrophage lipoprotein lipase (LPL) induces lipid accumulation and promotes atherosclerosis. However, the effects of lipoprotein hydrolysis products generated by LPL on macrophage-derived foam cell formation are not clearly understood. Thus, we analyzed the transcriptomic response to hydrolysis products via microarray analyses on RNA isolated from human THP-1 macrophages incubated with total lipoprotein hydrolysis products generated by LPL. The expression of 183 transcripts was significantly upregulated and 133 transcripts were significantly downregulated...
February 15, 2017: Lipids
https://www.readbyqxmd.com/read/28202906/bar502-a-dual-fxr-and-gpbar1-agonist-promotes-browning-of-white-adipose-tissue-and-reverses-liver-steatosis-and-fibrosis
#6
Adriana Carino, Sabrina Cipriani, Silvia Marchianò, Michele Biagioli, Chiara Santorelli, Annibale Donini, Angela Zampella, Maria Chiara Monti, Stefano Fiorucci
Non-alcoholic steatohepatitis (NASH) is a highly prevalent chronic liver disease. Here, we have investigated whether BAR502, a non-bile acid, steroidal dual ligand for FXR and GPBAR1, reverses steato-hepatitis in mice fed a high fat diet (HFD) and fructose. After 9 week, mice on HFD gained ≈30% of b.w (P < 0.01 versus naïve) and were insulin resistant. These overweighting and insulin resistant mice were randomized to receive HFD or HFD in combination with BAR502. After 18 weeks, HFD mice developed NASH like features with severe steato-hepatitis and fibrosis, increased hepatic content of triacylglycerol and cholesterol and expression of SREPB1c, FAS, ApoC2, PPARα and γ, α-SMA, α1 collagen and MCP1 mRNAs...
February 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28202387/varenicline-enhances-oxidized-ldl-uptake-by-increasing-expression-of-lox-1-and-cd36-scavenger-receptors-through-%C3%AE-7-nachr-in-macrophages
#7
Yuki Kanaoka, Mitsuhisa Koga, Keita Sugiyama, Kaoru Ohishi, Yasufumi Kataoka, Atsushi Yamauchi
Varenicline is a widely used and effective drug for smoking cessation. It is a partial agonist of the α4β2 nicotinic acetylcholine receptor (nAChR) and full agonist of α7 nAChR. We have reported that varenicline aggravates formation of atherosclerotic plaques through α7 nAChR in apolipoprotein E knockout mice. However, little is known about its effects on macrophages in atherosclerotic plaques. Here, we ascertained whether varenicline promotes oxidized low-density lipoprotein (oxLDL) uptake in mouse peritoneal macrophages in vitro and clarified its mechanism...
February 12, 2017: Toxicology
https://www.readbyqxmd.com/read/28186980/diet-induced-obesity-links-to-er-positive-breast-cancer-progression-via-lpa-pkd-1-cd36-signaling-mediated-microvascular-remodeling
#8
Liuyi Dong, Ye Yuan, Cynthia Opansky, Yiliang Chen, Irene Aguilera-Barrantes, Shiyong Wu, Rong Yuan, Qi Cao, Yee Chung Cheng, Daisy Sahoo, Roy L Silverstein, Bin Ren
Obesity increases cancer risk including breast cancer (BC). However, the direct regulatory mechanisms by which obesity promotes BC progression remain largely unknown. We show that lysophosphatidic acid/protein kinase D1 (LPA/PKD-1)-CD36 signaling is a bona fide breast cancer promoter via stimulating microvascular remodeling in chronic diet-induced obesity (DIO). We observed that the growth of an estrogen receptor (ER) positive breast cancer was markedly increased when compared to the lean control, and specifically accompanied by increased microvascular remodeling in a syngeneic BC model in female DIO mice...
February 6, 2017: Oncotarget
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/28183816/two-weeks-of-moderate-intensity-continuous-training-but-not-high-intensity-interval-training-increases-insulin-stimulated-intestinal-glucose-uptake
#10
Kumail Kumar Motiani, Anna M Savolainen, Jari-Joonas Eskelinen, Jussi Toivanen, Tamiko Ishizu, Minna Yli-Karjanmaa, Kirsi A Virtanen, Riitta Parkkola, Jukka Kapanen, Tove J Gronroos, Merja Haaparanta-Solin, Olof Solin, Nina Savisto, Markku Ahotupa, Eliisa Löyttyniemi, Juhani Knuuti, Pirjo Nuutila, Kari K Kalliokoski, Jarna C Hannukainen
Similar to muscles, the intestine is also insulin resistant in obese subjects and subjects with impaired glucose tolerance. Exercise training improves muscle insulin sensitivity, but its effects on intestinal metabolism are not known. We studied the effects of high intensity interval training (HIIT) and moderate intensity continuous training (MICT) on intestinal glucose and free fatty acid uptake from circulation in humans. Twenty-eight healthy middle-aged sedentary men were randomized for two weeks of HIIT or MICT...
February 9, 2017: Journal of Applied Physiology
https://www.readbyqxmd.com/read/28178563/lipid-metabolism-fuels-cancer-s-spread
#11
Zhuo Li, Yibin Kang
The ability to prospectively identify metastasis-initiating cells is essential for developing new anti-metastasis therapeutics. In a recent issue of Nature, Pascual et al. (2017) demonstrate that the fatty acid receptor CD36 marks a subpopulation of cancer cells with unique metastasis-initiating potential, highlighting a key role of lipid metabolism in metastatic colonization.
February 7, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28176216/pcsk9-targets-important-for-lipid-metabolism
#12
Rainer Schulz, Klaus-Dieter Schlüter
Ischemic heart disease is the main cause of death worldwide and it is accelerated by increased low-density lipoprotein (LDL) cholesterol (LDL-C) and/or lipoprotein (a) (Lp(a)) concentrations. Proprotein convertase subtilisin/kexin type 9 (PCSK9) alters both LDL-C and in part Lp(a) concentrations through its ability to induce degradation of the LDL receptor (LDLR). PCSK9, however, has additional targets which are potentially involved in lipid metabolism regulation such as the very low density lipoprotein receptor (VLDL), CD36 (cluster of differentiation 36) and the epithelial cholesterol transporter (NPC1L1) and it affects expression of apolipoprotein B48...
February 7, 2017: Clinical Research in Cardiology Supplements
https://www.readbyqxmd.com/read/28168203/microvesicles-correlated-with-components-of-metabolic-syndrome-in-men-with-type-2-diabetes-mellitus-and-lowered-testosterone-levels-but-were-unaltered-by-testosterone-therapy
#13
Jaco Botha, Line Velling Magnussen, Morten Hjuler Nielsen, Tine Bo Nielsen, Kurt Højlund, Marianne Skovsager Andersen, Aase Handberg
Aims. To investigate how circulating microvesicle phenotypes correlate with insulin sensitivity, body composition, plasma lipids, and hepatic fat accumulation. We hypothesized that changes elicited by testosterone replacement therapy are reflected in levels of microvesicles. Methods. Thirty-nine type 2 diabetic males with lowered testosterone levels were assigned to either testosterone replacement therapy or placebo and evaluated at baseline and after 24 weeks. Microvesicles were analysed by flow cytometry and defined as lactadherin-binding particles within the 0...
2017: Journal of Diabetes Research
https://www.readbyqxmd.com/read/28166864/flow-cytometry-analysis-of-platelet-populations-usefulness-for-monitoring-the-storage-lesion-in-pooled-buffy-coat-platelet-concentrates
#14
Dušan Vučetić, Vesna Ilić, Danilo Vojvodić, Vesna Subota, Milena Todorović, Bela Balint
BACKGROUND: Early detection of the platelet storage lesion is still a challenge in transfusion practice. Using flow cytometry, we evaluated the appearance of the storage lesion, based on the expression of platelet activation markers, in total platelets and platelet populations. MATERIALS AND METHODS: Buffy-coat-derived platelet concentrates were stored under standard conditions for 5 days. The expression of activation antigens CD42b, CD36, CD62p and phosphatidylserine on total platelets and populations of small, medium-sized and large platelets was analysed by flow cytometry on storage days 1, 3 and 5...
December 21, 2016: Blood Transfusion, Trasfusione del Sangue
https://www.readbyqxmd.com/read/28163099/17%C3%AE-estradiol-protects-against-the-effects-of-a-high-fat-diet-on-cardiac-glucose-lipid-and-nitric-oxide-metabolism-in-rats
#15
Sonja Zafirovic, Milan Obradovic, Emina Sudar-Milovanovic, Aleksandra Jovanovic, Julijana Stanimirovic, Alan J Stewart, Samantha J Pitt, Esma R Isenovic
The aim of this study was to investigate the in vivo effects of 17β-estradiol (E2) on myocardial metabolism and inducible nitric oxide synthase (iNOS) expression/activity in obese rats. Male Wistar rats were fed with a normal or a high fat (HF) diet (42% fat) for 10 weeks. Half of the HF fed rats were treated with a single dose of E2 while the other half were placebo-treated. 24 h after treatment animals were sacrificed. E2 reduced cardiac free fatty acid (FFA) (p < 0.05), L-arginine (p < 0.01), iNOS mRNA (p < 0...
February 2, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28154371/oxidative-stress-and-calcium-dysregulation-by-palmitate-in-type-2-diabetes
#16
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/28150942/identification-of-inhibitors-of-cd36-amyloid-beta-binding-as-potential-agents-for-alzheimer-s-disease
#17
Deborah Doens, Pedro A Valiente, Adelphe M Mfuh, Anh X T Vo, Adilia Tristan, Lizmar Carreño, Mario Quijada, Vu T Nguyen, George Perry, Oleg V Larionov, Ricardo Lleonart, Patricia L Fernández
Neuroinflammation is one of the hallmarks of Alzheimer's disease pathology. Amyloid β has a central role in microglia activation and the subsequent secretion of inflammatory mediators that are associated with neuronal toxicity. The recognition of amyloid β by microglia depends on the expression of several receptors implicated in the clearance of amyloid and in cell activation. CD36 receptor expressed on microglia interacts with fibrils of amyloid inducing the release of proinflammatory cytokines and amyloid internalization...
February 15, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28150475/relationship-between-fat-cd36-protein-in-skeletal-muscle-and-whole-body-fat-oxidation-in-endurance-trained-mice
#18
Jisu Kim, Kiwon Lim
Purpose: We investigated the effects of endurance training on the expression of long-chain fatty acid transport proteins in the skeletal muscle and whole-body fat oxidation during endurance exercise. Methods: Seven-week-old male ICR mice (n = 12) were divided into 2 groups, namely, Sed (sedentary; non-trained) and Tr (endurance-trained) groups. The Tr group was adapted to treadmill training at a fixed intensity (15 m/min, 8° slope) for 3 days. Next, the exercise intensity was increased while maintaining the 8° slope...
December 31, 2016: Journal of Exercise Nutrition & Biochemistry
https://www.readbyqxmd.com/read/28146135/the-transcription-profile-unveils-the-cardioprotective-effect-of-aspalathin-against-lipid-toxicity-in-an-in-vitro-h9c2-model
#19
Rabia Johnson, Phiwayinkosi V Dludla, Christo J F Muller, Barbara Huisamen, M Faadiel Essop, Johan Louw
Aspalathin, a C-glucosyl dihydrochalcone, has previously been shown to protect cardiomyocytes against hyperglycemia-induced shifts in substrate preference and subsequent apoptosis. However, the precise gene regulatory network remains to be elucidated. To unravel the mechanism and provide insight into this supposition, the direct effect of aspalathin in an isolated cell-based system, without the influence of any variables, was tested using an H9c2 cardiomyocyte model. Cardiomyocytes were exposed to high glucose (33 mM) for 48 h before post-treatment with or without aspalathin...
January 31, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28131831/response-of-genes-involved-in-lipid-metabolism-in-rat-epididymal-white-adipose-tissue-to-different-fasting-conditions-after-long-term-fructose-consumption
#20
Jin-Xiu Li, Da-Zhi Ke, Ling Yao, Shang Wang, Peng Ma, Li Liu, Guo-Wei Zuo, Li-Rong Jiang, Jian-Wei Wang
There has been much concern regarding the dietary fructose contributes to the development of metabolic syndrome. High-fructose diet changes the expression of genes involved in lipid metabolism. Levels of a number of hepatic lipogenic enzymes are increased by a high-carbohydrate diet in fasted-refed model rats/mice. Both the white adipose tissue (WAT) and the liver play a key role in the maintenance of nutrient homeostasis. Here, the aim of this study was to analyze the expression of key genes related to lipid metabolism in epididymal WAT (eWAT) in response to different fasting condition after long-term chronic fructose consumption...
January 25, 2017: Biochemical and Biophysical Research Communications
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