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https://www.readbyqxmd.com/read/28445528/baicalein-protects-rat-insulinoma-ins-1-cells-from-palmitate-induced-lipotoxicity-by-inducing-ho-1
#1
Hyun Jeong Kwak, Dongki Yang, Yongha Hwang, Hee-Sook Jun, Hyae Gyeong Cheon
OBJECTIVE: β-Cell dysfunction plays a central role in the pathogenesis of type 2 diabetes (T2D), and the identification of novel approaches to improve β-cell function is essential to treat this disease. Baicalein, a flavonoid originally isolated from the root of Scutellaria Baicalensis, has been shown to have beneficial effects on β-cell function. Here, the authors investigated the molecular mechanism responsible for the protective effects of baicalein against palmitate (PA)-induced impaired β-cell function, and placed focus on the role of heme oxygenase (HO)-1...
2017: PloS One
https://www.readbyqxmd.com/read/28441156/interpreting-lipoproteins-in-nonalcoholic-fatty-liver-disease
#2
Katriina Nemes, Fredrik Åberg
PURPOSE OF REVIEW: The pathophysiologies of nonalcoholic fatty liver disease (NAFLD), metabolic syndrome, and cardiovascular disease are closely interlinked and associated with atherogenic dyslipidemia. Liver and cardiovascular disease may silently progress to advanced stages if alarming signs, such as abdominal obesity, elevated fasting and postprandial triglycerides, and low HDL cholesterol are overlooked. We review the metabolic mechanisms in NAFLD at the cellular level in the context of standard clinical lipid measurements...
April 22, 2017: Current Opinion in Lipidology
https://www.readbyqxmd.com/read/28440734/cholinergic-activation-suppresses-palmitate-induced-macrophage-activation-and-improves-acylation-stimulating-protein-resistance-in-co-cultured-adipocytes
#3
Jing Wu, Zhou-Yang Jiao, Rui-Zhen Li, Hui-Ling Lu, Hao-Hao Zhang, Katherine Cianflone
Acylation-stimulating protein (ASP), produced through activation of the alternative complement immune system, modulates lipid metabolism. Using a trans-well co-culture cell model, the mitigating role of α7-nicotinic acetylcholine receptor (α7nAChR)-mediated cholinergic pathway on ASP resistance was evaluated. ASP signaling in adipocytes via its receptor C5L2 and signaling intermediates Gαq, Gβ, phosphorylated protein kinase C-α, and protein kinase C-ζ were markedly suppressed in the presence of TNFα or medium from palmitate-treated RAW264...
May 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28437863/sirt3-acts-as-a-negative-regulator-of-autophagy-dictating-hepatocyte-susceptibility-to-lipotoxicity
#4
Songtao Li, Xiaobing Dou, Hua Ning, Qing Song, Wei Wei, Ximei Zhang, Chen Shen, Jiaxin Li, Changhao Sun, Zhenyuan Song
Lipotoxicity induced by saturated fatty acids (SFAs) plays a central role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD); however, the exact mechanism(s) remain to be fully elucidated. SIRT3 is an NAD(+) -dependent deacetylase primarily located inside mitochondria. In this study, we demonstrated that a SFAs-rich high-fat diet (HFD) was more detrimental to the liver than an isocaloric unsaturated FAs-rich HFD. Unexpectedly, SIRT3 expression/activity were significantly elevated in the livers of mice exposed to the SFAs-rich HFD...
April 24, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28430962/ulk1-prevents-cardiac-dysfunction-in-obesity-through-autophagy-meditated-regulation-of-lipid-metabolism
#5
Minae An, Dong-Ryeol Ryu, Jang Won Park, Ji Ha Choi, Eun-Mi Park, Kyung Eun Lee, Minna Woo, Minsuk Kim
Aims: Autophagy is essential to maintain tissue homeostasis, particularly in long-lived cells such as cardiomyocytes. Whereas many studies support the importance of autophagy in the mechanisms underlying obesity-related cardiac dysfunction, the role of autophagy in cardiac lipid metabolism remains unclear. In the heart, lipotoxicity is exacerbated by cardiac lipoprotein lipase (LPL), which mediates accumulation of fatty acids to the heart through intravascular triglyceride (TG) hydrolysis...
April 17, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28419197/inhibition-of-sarcolemmal-fat-cd36-by-sulfo-n-succinimidyl-oleate-rapidly-corrects-metabolism-and-restores-function-in-the-diabetic-heart-following-hypoxia-reoxygenation
#6
Latt S Mansor, Maria da Luz Sousa Fialho, Georgina Yea, Will A Coumans, James A West, Matthew Kerr, Carolyn A Carr, Joost J F P Luiken, Jan F C Glatz, Rhys D Evans, Julian L Griffin, Damian J Tyler, Kieran Clarke, Lisa C Heather
Aims: The type 2 diabetic heart oxidizes more fat and less glucose, which can impair metabolic flexibility and function. Increased sarcolemmal fatty acid translocase (FAT/CD36) imports more fatty acid into the diabetic myocardium, feeding increased fatty acid oxidation and elevated lipid deposition. Unlike other metabolic modulators that target mitochondrial fatty acid oxidation, we proposed that pharmacologically inhibiting fatty acid uptake, as the primary step in the pathway, would provide an alternative mechanism to rebalance metabolism and prevent lipid accumulation following hypoxic stress...
April 17, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28411199/impact-of-fabp1-scp-2-scp-x-gene-ablation-tko-on-hepatic-phytol-metabolism-in-mice
#7
Stephen M Storey, Huan Huang, Avery L McIntosh, Gregory G Martin, Ann B Kier, Friedhelm Schroeder
Studies in vitro have suggested that both sterol carrier protein-2/sterol carrier protein-x (Scp-2/Scp-x) and liver fatty acid binding protein (Fabp1) gene products facilitate hepatic uptake and metabolism of lipotoxic dietary phytol. However, interpretation of physiological function in mice singly gene ablated in the Scp-2/Scp-x has been complicated by concomitant upregulation of FABP1. The work presented herein provides several novel insights: i) An ANS displacement assay showed that neither SCP-2 nor L-FABP bound phytol, but both had high affinity for its metabolite, phytanic acid; ii) GC/MS studies with phytol-fed wild-type (WT) and Fabp1/Scp-2/SCP-x gene ablated (TKO) mice showed that TKO exacerbated hepatic accumulation of phytol metabolites in vivo in females and less so in males...
April 14, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28397088/combination-of-anti-hypertensive-drugs-a-molecular-dynamics-simulation-study
#8
Abbas Yousefpour, Hamid Modarress, Fatemeh Goharpey, Sepideh Amjad-Iranagh
The anti-hypertensive drugs amlodipine, atenolol and lisinopril, in ordinary and PEGylated forms, with different combined-ratios, were studied by molecular dynamics simulations using GROMACS software. Twenty simulation systems were designed to evaluate the interactions of drug mixtures with a dimyristoylphosphatidylcholine (DMPC) lipid bilayer membrane, in the presence of water molecules. In the course of simulations, various properties of the systems were investigated, including drug location, diffusion and mass distribution in the membrane; drug orientation; the lipid chain disorder as a result of drug penetration into the DMPC membrane; the number of hydrogen bonds; and drug surface area...
May 2017: Journal of Molecular Modeling
https://www.readbyqxmd.com/read/28385803/insulin-receptor-signaling-in-pomc-but-not-agrp-neurons-controls-adipose-tissue-insulin-action
#9
Andrew C Shin, Nika Filatova, Claudia Lindtner, Tiffany Chi, Seta Degann, Douglas Oberlin, Christoph Buettner
Insulin is a key regulator of adipose tissue lipolysis and impaired adipose tissue insulin action results in unrestrained lipolysis and lipotoxicity, which are hallmarks of the metabolic syndrome and diabetes. Insulin regulates adipose tissue metabolism through direct effects on adipocytes and through signaling in the CNS by dampening sympathetic outflow to the adipose tissue. Here we examined the role of insulin signaling in agouti-related protein (AgRP) and pro-opiomelanocortin (POMC) neurons in regulating both hepatic and adipose tissue insulin action...
April 6, 2017: Diabetes
https://www.readbyqxmd.com/read/28385694/phosphatidylcholine-transfer-protein-stard2-promotes-microvesicular-steatosis-and-liver-injury-in-murine-experimental-steatohepatitis
#10
Hayley Tenielle Nicholls, Jason L Hornick, David E Cohen
Mice fed a methionine and choline deficient (MCD) diet develop steatohepatitis that recapitulates key features of nonalcoholic steatohepatitis (NASH) in humans. Phosphatidylcholine is the most abundant phospholipid in the surfactant monolayer that coats and stabilizes lipid droplets within cells, and choline is required for its major biosynthetic pathway. Phosphatidylcholine-transfer protein (PC-TP), which exchanges phosphatidylcholine among membranes, is enriched in hepatocytes. PC-TP also regulates fatty acid metabolism through interactions with thioesterase superfamily member 2...
April 6, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28375738/sirt3-deficiency-increased-the-vulnerability-of-pancreatic-beta-cells-to-oxidative-stress-induced-dysfunction
#11
Yu Zhou, Arthur C K Chung, Rongrong Fan, Heung Man Lee, Gang Xu, Brian Tomlinson, Juliana C N Chan, Alice P S Kong
AIMS: Hyperlipidemia-induced oxidative stress is considered to be one of the main pathogenic factors that contribute to pancreatic beta cell dysfunction in the development of type 2 diabetes (T2D). Sirtuin 3 (Sirt3) is abundantly expressed in the mitochondria as an NAD(+)-dependent deacetylase and regulates mitochondrial adaptive responses to oxidative stress. We examined the antioxidant defense mechanism of Sirt3 in pancreatic beta cells in the context of hyperlipidemia. RESULTS: Chronic high-fat diet (HFD) feeding caused elevated oxidative stress accompanied by reduced Sirt3 expression in the pancreatic beta cells of wild-type mice...
April 4, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28374891/short-term-hypoxia-reverses-ox-ldl-induced-cd36-and-glut4-switching-metabolic-pathways-in-h9c2-cardiomyoblast-cells
#12
Yeh-Peng Chen, Hsi-Hsien Hsu, Rathinasamy Baskaran, Su-Ying Wen, Chia-Yao Shen, Cecilia-Hsuan Day, Tsung-Jung Ho, Viswanadha Vijaya Padma, Wei-Wen Kuo, Chih-Yang Huang
High levels of circulating low-density lipoproteins (LDL, plasma proteins that carry cholesterol and triglycerides) are associated with type 2 diabetes, arteriosclerosis, obesity and hyperlipidemia. In the heart, the accumulation of oxidized low-density lipoprotein (Ox-LDL) has been proposed to play a role in the development of cardiovascular disease. We obtain cholesterol from animals and animal-derived foods such as milk, eggs and cheese. In previous studies, the ratio of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) was shown to be important for our health...
April 4, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28373637/cytoprotective-effects-and-mechanisms-of-%C3%AE-17-fatty-acid-desaturase-in-injured-human-umbilical-vein-endothelial-cells-huvecs
#13
Haoyu Zhou, Chengming Wang
BACKGROUND The beneficial effect of Δ-17 FAD is poorly understood. The aim of this study was to investigate the protective mechanism of fatty acids against atherosclerotic (AS) damage induced by oxidized low-density lipoprotein (ox-LDL) in human umbilical vein endothelial cells (HUVECs), and to identify the molecular mechanisms involved. MATERIAL AND METHODS The ox-LDL was used to induce lipotoxicity in HUVECs to establish a model of oxidative injury. HUVECs were transfected with Δ-17FAD lentivirus to induce cytoprotective effects...
April 4, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28373293/lipid-metabolism-and-its-implications-for-type-1-diabetes-associated-cardiomyopathy
#14
Rebecca H Ritchie, Eser J Zerenturk, Darnel Prakoso, Anna C Calkin
Diabetic cardiomyopathy was first defined over four decades ago. It was observed in small post-mortem studies of diabetic patients who suffered from concomitant heart failure despite the absence of hypertension, coronary disease or other likely causal factors, as well as in large population studies such as the Framingham Heart Study. Subsequent studies continue to demonstrate an increased incidence of heart failure in the setting of diabetes independent of established risk factors, suggesting direct effects of diabetes on the myocardium...
April 3, 2017: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/28359085/osteonecrosis-of-the-femoral-head-lipotoxicity-exacerbation-in-msc-and-modifications-of-the-bone-marrow-fluid
#15
Celine Gillet, Antoine Dalla Valle, Nathalie Gaspard, Delphine Spruyt, Pascale Vertongen, Jessica Lechanteur, Sabrina Rigutto, Elena-Raluca Dragan, Audrey Heuschling, Valerie Gangji, Joanne Rasschaert
Osteonecrosis of the femoral head (ON) is a multifactorial bone disease that can evolve to a progressive destruction of the hip joint. Different pathogenic processes have been proposed, among them, an increase of bone marrow (BM) fat resulting from adipocyte accumulation. Marrow adipocytes are active BM residents that influence the microenvironment by releasing cytokines, adipokines, and free fatty acids (FA). We explored the impact of palmitate (Palm) and oleate on function and survival of BM-derived mesenchymal stromal cells (MSC) of osteonecrotic patients (ONMSC) and healthy volunteers...
March 1, 2017: Endocrinology
https://www.readbyqxmd.com/read/28351695/antihyperlipidemic-and-hepatoprotective-effects-of-gardenin-a-in-cellular-and-high-fat-diet-fed-rodent-models
#16
Erenius Toppo, S Sylvester Darvin, S Esakkimuthu, A Stalin, K Balakrishna, K Sivasankaran, P Pandikumar, S Ignacimuthu, N A Al-Dhabi
The gum of Gardenia resinifera Roth., is one of the important drugs used in the Indian system of medicine and a source of unique polymethoxylated flavones. This study was aimed to evaluate the antihyperlipidemic and anti-NAFLD effects of Gardenin A (Gar-A) from G. resinifera gum using in vitro and in vivo models. Gar-A was isolated from G. resinifera gum and was identified on the basis of the physical and spectral data. Toxicity of Gar-A to HepG2 cells was evaluated using MTT assay. The ability of Gar-A to reduce steatosis was assessed using oleate-palmitate induced HepG2 cell lines by estimating the lipid levels by ORO staining and by estimating the intracellular triglyceride content...
May 1, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28339731/obesity-associated-cardiac-pathogenesis-in-broiler-breeder-hens-development-of-metabolic-cardiomyopathy2-3
#17
C Y Chen, Y F Huang, Y J Ko, Y J Liu, Y H Chen, R L Walzem, S E Chen
Feed intake is typically restricted (R) in broiler hens to avoid obesity and improve egg production and livability. To determine whether improved heart health contributes to improved livability, fully adult 45-week-old R hens were allowed to consume feed to appetite (ad libitum; AL) up to 10 wk (70 d). Mortality, contractile functions, and morphology at 70 d, and measurements of cardiac hypertrophic remodeling at 7 d and 21 d were made and compared between R and AL hens. Outcomes for cardiac electrophysiology and mortality, reported separately, found increased mortality in AL hens in association with cardiac pathological hypertrophy and contractile dysfunction...
February 22, 2017: Poultry Science
https://www.readbyqxmd.com/read/28339345/alanine-aminotransferase-is-a-marker-of-lipotoxicity-consequences-and-hyperandrogenemia-in-women-with-polycystic-ovary-syndrome
#18
Matea Belan, Chloé Pelletier, Jean-Patrice Baillargeon
BACKGROUND: Several studies have reported higher levels of Alanine aminotransferase (ALT) in women with polycystic ovary syndrome (PCOS) compared with control subjects. Plasma ALT levels are considered a marker of hepatic lipotoxicity because of their significant associations with different hepatic metabolic dysfunctions, such as hepatic steatosis and hepatic insulin resistance. METHODS: Retrospective chart review aiming to assess, in PCOS women, the relationship between ALT levels and measures of lipotoxicity consequences that are available clinically, both during fasting and using the oral glucose tolerance test...
April 2017: Metabolic Syndrome and related Disorders
https://www.readbyqxmd.com/read/28337030/prenatal-steroid-administration-leads-to-adult-pericardial-and-hepatic-steatosis-in-male-baboons
#19
A H Kuo, J Li, C Li, H F Huber, M Schwab, P W Nathanielsz, G D Clarke
Developmental programming studies indicate that glucocorticoids modify fetal development. We hypothesized that administration of the synthetic glucocorticoid (sGC) betamethasone to pregnant baboons at doses and stages of fetal life equivalent to human obstetric practice to decrease premature offspring morbidity and mortality, programs lipid metabolism. In 10-year-old male baboons (human equivalent 40) exposed in fetal life to betamethasone or saline, we quantified pericardial fat and hepatic lipid content with magnetic resonance imaging and spectroscopy...
April 18, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28323924/guanabenz-sensitizes-pancreatic-%C3%AE-cells-to-lipotoxic-endoplasmic-reticulum-stress-and-apoptosis
#20
Baroj Abdulkarim, Miriam Hernangomez, Mariana Igoillo Esteve, Daniel A Cunha, Lorella Marselli, Piero Marchetti, Laurence Ladriere, Miriam Cnop
Deficient as well as excessive/prolonged endoplasmic reticulum (ER) stress signaling can lead to pancreatic β cell failure and the development of diabetes. Saturated free fatty acids (FFAs) such as palmitate induce lipotoxic ER stress in pancreatic β cells. One of the main ER stress response pathways is under the control of the protein kinase R-like endoplasmic reticulum kinase (PERK), leading to phosphorylation of the eukaryotic translation initiation factor 2 (eIF2α). The antihypertensive drug guanabenz has been shown to inhibit eIF2α dephosphorylation and protect cells from ER stress...
March 1, 2017: Endocrinology
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