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https://www.readbyqxmd.com/read/28087336/oleate-induces-katp-channel-dependent-hyperpolarisation-in-mouse-hypothalamic-glucose-excited-neurones-without-altering-cellular-energy-charge
#1
Selma Dadak, Craig Beall, Julia M Vlachaki Walker, Marc Pm Soutar, Rory J McCrimmon, Michael L J Ashford
The unsaturated fatty acid, oleate exhibits anorexigenic properties reducing food intake and hepatic glucose output. However, its mechanism of action in the hypothalamus has not been fully determined. This study investigated the effects of oleate and glucose on GT1-7 mouse hypothalamic cells (a model of glucose-excited (GE) neurones) and mouse arcuate nucleus (ARC) neurones. Whole-cell and perforated patch-clamp recordings, immunoblotting and cell energy status measures were used to investigate oleate and glucose sensing properties of mouse hypothalamic neurones...
January 9, 2017: Neuroscience
https://www.readbyqxmd.com/read/28072841/a-small-insulinomimetic-molecule-also-improves-insulin-sensitivity-in-diabetic-mice
#2
Sandip Mukherjee, Mrittika Chattopadhyay, Sushmita Bhattacharya, Suman Dasgupta, Sahid Hussain, Saitanya K Bharadwaj, Dhrubajyoti Talukdar, Abul Usmani, Bhola S Pradhan, Subeer S Majumdar, Pronobesh Chattopadhyay, Satinath Mukhopadhyay, Tushar K Maity, Mihir K Chaudhuri, Samir Bhattacharya
Dramatic increase of diabetes over the globe is in tandem with the increase in insulin requirement. This is because destruction and dysfunction of pancreatic β-cells are of common occurrence in both Type1 diabetes and Type2 diabetes, and insulin injection becomes a compulsion. Because of several problems associated with insulin injection, orally active insulin mimetic compounds would be ideal substitute. Here we report a small molecule, a peroxyvanadate compound i.e. DmpzH[VO(O2)2(dmpz)], henceforth referred as dmp, which specifically binds to insulin receptor with considerable affinity (KD-1...
2017: PloS One
https://www.readbyqxmd.com/read/28066800/cd36-deficiency-impairs-the-small-intestinal-barrier-and-induces-subclinical-inflammation-in-mice
#3
Vincenza Cifarelli, Stoyan Ivanov, Yan Xie, Ni-Huiping Son, Brian T Saunders, Terri A Pietka, Trevor M Shew, Jun Yoshino, Sinju Sundaresan, Nicholas O Davidson, Ira J Goldberg, Andrew E Gelman, Bernd H Zinselmeyer, Gwendalyn J Randolph, Nada A Abumrad
BACKGROUND & AIMS: CD36 has immuno-metabolic actions and is abundant in the small intestine on epithelial, endothelial and immune cells. We examined the role of CD36 in gut homeostasis using mice null for CD36 (CD36KO) and with CD36 deletion specific to enterocytes (Ent-CD36KO) or endothelial cells (EC-CD36KO). METHODS: Intestinal morphology was evaluated using immunohistochemistry and electron microscopy (EM). Intestinal inflammation was determined from neutrophil infiltration and expression of cytokines, toll-like receptors and COX-2...
January 2017: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28062415/cardiomyocyte-specific-ablation-of-cd36-accelerates-the-progression-from-compensated-cardiac-hypertrophy-to-heart-failure
#4
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/28060419/a-molecular-roadmap-of-definitive-erythropoiesis-from-human-induced-pluripotent-stem-cells
#5
Muhammad A Razaq, Stephen Taylor, David J Roberts, Lee Carpenter
Human induced pluripotent stem cells (hiPSCs) are being considered for use in understanding haematopoietic disorders and as a potential source of in vitro manufactured red cells. Here, we show that hiPSCs are able to recapitulate various stages of developmental erythropoiesis. We show that primitive erythroblasts arise first, express CD31(+) with CD235a(+) , embryonic globins and red cell markers, but fail to express the hallmark red cell transcripts of adult erythropoiesis. When hiPSC-derived CD45(+) CD235a(-) haematopoietic progenitors are isolated on day 12 and further differentiated on OP9 stroma, they selectively express CD36(+) and CD235a(+) , adult erythroid transcripts for transcription factors (e...
January 6, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28059487/%C3%AE-tocopheryl-phosphate-induces-vegf-expression-via-cd36-pi3k%C3%AE-in-thp-1-monocytes
#6
Jean-Marc Zingg, Angelo Azzi, Mohsen Meydani
The CD36 scavenger receptor binds several ligands and mediates ligand uptake and ligand-dependent signal transduction and gene expression, events that may involve CD36 internalization. Here we show that CD36 internalization in THP-1 monocytes is triggered by α-tocopherol (αT) and more strongly by α-tocopheryl phosphate (αTP) and EPC-K1, a phosphate diester of αTP and L-ascorbic acid. αTP-triggered CD36 internalization is prevented by the specific covalent inhibitor of selective lipid transport by CD36, sulfo-N-succinimidyl oleate (SSO)...
January 6, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28053235/inactivation-of-rab11a-gtpase-in-macrophages-facilitates-phagocytosis-of-apoptotic-neutrophils
#7
Chunling Jiang, Zheng Liu, Rong Hu, Lulong Bo, Richard D Minshall, Asrar B Malik, Guochang Hu
The timely and efficient clearance of apoptotic neutrophils by macrophages (efferocytosis) is required for the resolution of inflammation and tissue repair, but the regulatory mechanisms remain unclear. In this study, we investigated the role of the small GTPase Ras-related protein in brain (Rab)11a in regulating efferocytosis, and on this basis the resolution of inflammatory lung injury. We observed that apoptotic neutrophil feeding induced a rapid loss of Rab11a activity in bone marrow-derived macrophages and found that depletion of Rab11a in macrophages by small interfering RNA dramatically increased the phagocytosis of apoptotic neutrophils compared with control cells...
January 4, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28052815/how-do-macrophages-sense-modified-low-density-lipoproteins
#8
REVIEW
Dimitry A Chistiakov, Alexandra A Melnichenko, Alexander N Orekhov, Yuri V Bobryshev
In atherosclerosis, serum lipoproteins undergo various chemical modifications that impair their normal function. Modification of low density lipoprotein (LDL) such as oxidation, glycation, carbamylation, glucooxidation, etc. makes LDL particles more proatherogenic. Macrophages are responsible for clearance of modified LDL to prevent cytotoxicity, tissue injury, inflammation, and metabolic disturbances. They develop an advanced sensing arsenal composed of various pattern recognition receptors (PRRs) capable of recognizing and binding foreign or altered-self targets for further inactivation and degradation...
December 28, 2016: International Journal of Cardiology
https://www.readbyqxmd.com/read/28040583/ros-via-btk-p300-stat1-ppar%C3%AE-signaling-activation-mediates-cholesterol-crystals-induced-cd36-expression-and-foam-cell-formation
#9
Sivareddy Kotla, Nikhlesh K Singh, Gadiparthi N Rao
In understanding the mechanisms of cholesterol in the pathogenesis of atherosclerosis, previous studies from other laboratories have demonstrated that cholesterol crystals (CC) induce scavenger receptor CD36 expression and NLRP3-mediated inflammasome formation. In elucidating the mechanisms by which CC could enhance CD36 expression and foam cell formation, here we report that CC via NADPH and xanthine oxidases-mediated ROS production activates BTK, a non-receptor tyrosine kinase. In addition, CC induce p300 tyrosine phosphorylation and activation in a BTK-dependent manner, which in turn, leads to STAT1 acetylation and its interaction with PPARγ in CD36 expression, oxLDL uptake and foam cell formation...
December 7, 2016: Redox Biology
https://www.readbyqxmd.com/read/28038998/activation-of-ampk-by-berberine-induces-hepatic-lipid-accumulation-by-upregulation-of-fatty-acid-translocase-cd36-in-mice
#10
You-Jin Choi, Kang-Yo Lee, Seung-Hwan Jung, Hyung Sik Kim, Gayong Shim, Mi-Gyeong Kim, Yu-Kyoung Oh, Seon-Hee Oh, Dae Won Jun, Byung-Hoon Lee
Emerging evidence has shown that berberine has a protective effect against metabolic syndrome such as obesity and type II diabetes mellitus by activating AMP-activated protein kinase (AMPK). AMPK induces CD36 trafficking to the sarcolemma for fatty acid uptake and oxidation in contracting muscle. However, little is known about the effects of AMPK on CD36 regulation in the liver. We investigated whether AMPK activation by berberine affects CD36 expression and fatty acid uptake in hepatocytes and whether it is linked to hepatic lipid accumulation...
December 28, 2016: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28013071/from-fat-to-fat-cd36-sr-b2-understanding-the-regulation-of-cellular-fatty-acid-uptake
#11
Jan F C Glatz, Joost J F P Luiken
The molecular mechanisms underlying the cellular uptake of long-chain fatty acids and the regulation of this process have been elucidated in appreciable detail in the last decades. Two main players in this field, each discovered in the early 1990s, are (i) a membrane-associated protein first identified in adipose ('fat') tissue and referred to as putative fatty acid translocase (FAT)/CD36 (now officially designated as SR-B2) which facilitates the transport of fatty acids across the plasma membrane, and (ii) the family of transcription factors designated peroxisome proliferator-activated receptors (PPARα, PPARγ, and PPARβ/δ) for which fatty acids and fatty acid metabolites are the preferred ligand...
December 21, 2016: Biochimie
https://www.readbyqxmd.com/read/28007964/peroxisome-proliferator-activated-receptor-%C3%AE-accelerates-%C3%AE-chlorofatty-acid-catabolism
#12
Elisa N D Palladino, Wen-Yi Wang, Carolyn J Albert, Cedric Langhi, Ángel Baldán, David A Ford
α-Chlorofatty aldehydes are generated from myeloperoxidase (MPO)-derived HOCl targeting plasmalogens, and are subsequently oxidized to α-chlorofatty acids (α-ClFA). The catabolic pathway for α-ClFA is initiated by ω-oxidation. Here we examine peroxisome proliferator-activated receptor-α; (PPAR-α) activation as a mechanism to increase α-ClFA catabolism. Pretreating both HepG2 cells and primary mouse hepatocytes with the PPAR-α agonist Wy 14643 increased the production of α-chlorodicarboxylic acids (α-ClDCA) in cells treated with exogenous α-ClFA...
December 22, 2016: Journal of Lipid Research
https://www.readbyqxmd.com/read/28007141/genetic-and-pharmacological-inhibition-of-trem-1-limits-the-development-of-experimental-atherosclerosis
#13
Jeremie Joffre, Stephane Potteaux, Lynda Zeboudj, Xavier Loyer, Amir Boufenzer, Ludivine Laurans, Bruno Esposito, Marie Vandestienne, Saskia C A de Jager, Carole Hénique, Ivana Zlatanova, Soraya Taleb, Patrick Bruneval, Alain Tedgui, Ziad Mallat, Sebastien Gibot, Hafid Ait-Oufella
BACKGROUND: Innate immune responses activated through myeloid cells contribute to the initiation, progression, and complications of atherosclerosis in experimental models. However, the critical upstream pathways that link innate immune activation to foam cell formation are still poorly identified. OBJECTIVES: This study sought to investigate the hypothesis that activation of the triggering receptor expressed on myeloid cells (TREM-1) plays a determinant role in macrophage atherogenic responses...
December 27, 2016: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/28005078/hypericin-mediated-sonodynamic-therapy-induces-autophagy-and-decreases-lipids-in-thp-1-macrophage-by-promoting-ros-dependent-nuclear-translocation-of-tfeb
#14
Xuesong Li, Xin Zhang, Longbin Zheng, Jiayuan Kou, Zhaoyu Zhong, Yueqing Jiang, Wei Wang, Zengxiang Dong, Zhongni Liu, Xiaobo Han, Jing Li, Ye Tian, Yajun Zhao, Liming Yang
Lipid catabolism disorder is the primary cause of atherosclerosis. Transcription factor EB (TFEB) prevents atherosclerosis by activating macrophage autophagy to promote lipid degradation. Hypericin-mediated sonodynamic therapy (HY-SDT) has been proved non-invasively inducing THP-1-derived macrophage apoptosis; however, it is unknown whether macrophage autophagy could be triggered by HY-SDT to influence cellular lipid catabolism via regulating TFEB. Here, we report that HY-SDT resulted in the time-dependent THP-1-derived macrophage autophagy activation through AMPK/AKT/mTOR pathway...
December 22, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/28003996/scavenger-receptor-class-b-type-i-a-cd36-related-protein-in-macrobrachium-nipponense-characterization-rna-interference-and-expression-analysis-with-different-dietary-lipid-sources
#15
Zhili Ding, Na Luo, Youqin Kong, Jingfen Li, Yixiang Zhang, Fang Cao, Jinyun Ye
The scavenger receptor class B, type I (SR-BI), is a member of the CD36 superfamily comprising transmembrane proteins involved in mammalian and fish lipid homeostasis regulation. We hypothesize that this receptor plays an important role in Macrobrachium nipponense lipid metabolism. However, little attention has been paid to SR-BI in commercial crustaceans. In the present study, we report a cDNA encoding M. nipponense scavenger receptor class B, type I (designated as MnSR-BI), obtained from a hepatopancreas cDNA library...
2016: International Journal of Genomics
https://www.readbyqxmd.com/read/28003715/high-fructose-intake-impairs-the-hepatic-hypolipidemic-effects-of-a-high-fat-fish-oil-diet-in-c57bl-6-mice
#16
Joshua S Wooten, Tayler N Nick, Andrew Seija, Kaylee E Poole, Kelsey B Stout
BACKGROUND: Overnutrition of saturated fats and fructose is one of the major factors for the development of nonalcoholic fatty liver disease. Because omega-3 polyunsaturated fatty acids (n-3fa) have established lipid lowering properties, we tested the hypothesis that n-3fa prevents high-fat and fructose-induced fatty liver disease in mice. METHODS: Male C57BL/6J mice were randomly assigned to one of the following diet groups for 14 weeks: normal diet (ND), high-fat lard-based diet (HFD), HFD with fructose (HFD + Fru), high-fat fish-oil diet (FOD), or FOD + Fru...
December 2016: Journal of Clinical and Experimental Hepatology
https://www.readbyqxmd.com/read/28003580/identification-of-the-odor-active-volatile-compound-z-z-4-7-tridecadienal-as-a-potential-ligand-for-the-transmembrane-receptor-cd36
#17
Satoshi Tsuzuki, Takahiko Amitsuka, Tatsuya Okahashi, Yuki Kozai, Masayuki Yamasaki, Kazuo Inoue, Tohru Fushiki
Cluster of differentiation 36 (CD36) is a broadly expressed transmembrane protein that has multiple ligands, including oxidized low-density lipoproteins. We found recently that CD36 is expressed in olfactory sensory neurons and postulated that it plays a role in the detection of distinct odorants in the nasal cavity. To date, however, there have been few examples of attempts to identify CD36-recognizable odorants. In this study, by an in vitro assay using a peptide mimic of the receptor, we provided evidence that CD36 recognizes (Z,Z)-4,7-tridecadienal, an odor-active volatile compound that is known to occur in Katsuobushi (dried, fermented, and smoked skipjack tuna commonly used in Japanese cuisine as a seasoning) and in the preorbital secretion of male oribi...
2016: Biomedical Research
https://www.readbyqxmd.com/read/27997977/regulation-of-hepatocellular-fatty-acid-uptake-in-mouse-models-of-fatty-liver-disease-with-and-without-functional-leptin-signaling-roles-of-nfkb-and-srebp-1c-and-the-effects-of-spexin
#18
Jasmine F Ge, J L Walewski, D Anglade, P D Berk
The processes causing increased hepatic triglycerides (TGs) in mouse models of hepatic steatosis (HS) due to high fat diet (HFD)-induced obesity (DIO), EtOH consumption, or obesity mutations (ob/ob, db/db) are uncertain. This report summarizes two studies. Study 1 focused on regulation by five transcription factors (TFs) (NfKb, Srebp-lc, AMPK, PPARα, PPARγ) of seven, much-studied hepatic long-chain fatty acid (LCFA) transporters (FABPpm, CD36, FATPl, FATP2, FATP4, FATP5, & Caveolin-1 [CAV-1]), and expression of genes for enzymes of LCFA synthesis (SCD-1, FASN) in mice with HS from various causes...
September 2016: Seminars in Liver Disease
https://www.readbyqxmd.com/read/27995732/oxldl-antibody-inhibits-mcp-1-release-in-monocytes-macrophages-by-regulating-ca-2-k-channel-flow
#19
Jinyu Su, Hui Zhou, Xianyan Liu, Jan Nilsson, Gunilla Nordin Fredrikson, Ming Zhao
oxLDL peptide vaccine and its antibody adoptive transferring have shown a significantly preventive or therapeutic effect in atherosclerotic animal model. The molecular mechanism behind this is obscure. Here, we report that oxLDL induces MCP-1 release in monocytes/macrophages through their TLR-4 (Toll-like receptor 4) and ERK MAPK pathway and is calcium/potassium channel-dependent. Using blocking antibodies against CD36, TLR-4, SR-AI and LOX-1, only TLR-4 antibody was found to have an inhibitory effect and ERK MAPK-specific inhibitor (PD98059) was found to have a dramatic inhibitory effect compared to inhibitors of other MAPK group members (p38 and JNK MAPKs) on oxLDL-induced MCP-1 release...
December 20, 2016: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/27995417/high-density-lipoprotein-from-subjects-with-coronary-artery-disease-promotes-macrophage-foam-cell-formation-role-of-scavenger-receptor-cd36-and-erk-mapk-signaling
#20
S Sini, D Deepa, S Harikrishnan, N Jayakumari
Although high-density lipoprotein is atheroprotective, it can become dysfunctional in chronic inflammatory conditions and increase cardiovascular risk. We previously demonstrated that HDL from subjects with documented coronary artery disease is dysfunctional and is pro-oxidant/proinflammatory in macrophages. Here we examined the influence of dysfunctional/proinflammatory HDL (piHDL) on lipid accumulation in human macrophages, in comparison to functional HDL (nHDL). Exposure of macrophages to piHDL, in contrast to nHDL, resulted in oxidative stress and marked uptake of lipids from piHDL, leading to the formation of foam cell phenotype as noted by oil red O staining with concomitant increase in total cellular cholesterol content...
December 19, 2016: Molecular and Cellular Biochemistry
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