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lipotoxicity

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https://www.readbyqxmd.com/read/28548571/correlation-of-cdc42-activity-with-cell-proliferation-and-palmitate-mediated-cell-death-in-human-umbilical-cord-wharton-s-jelly-derived-mesenchymal-stromal-cells
#1
Jun Lu, Qinghua Wang, Lianghu Huang, Huiyue Dong, Lingjing Lin, Jianming Tan
RHO GTPases regulate cell migration, cell-cycle progression, and cell survival in response to extracellular stimuli. However, the regulatory effects of RHO GTPases in mesenchymal stromal cells (MSCs) are unclear. Herein, we show that CDC42 acts as an essential factor in regulating cell proliferation and also takes part in lipotoxic effects of palmitate in human umbilical cord Wharton's jelly derived MSCs (hWJ-MSCs). Cultured human bone marrow (hBM-MSCs), adipose tissue (hAD-MSCs), and umbilical cord Wharton's jelly (hWJ-MSCs) derived cells had varying pro-inflammatory cytokine secretion levels and cell death rates when treated by palmitate...
May 26, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28544394/muscle-metabolic-alterations-induced-by-genetic-ablation-of-4e-bp1-and-4e-bp2-in-response-to-diet-induced-obesity
#2
Olivier Le Bacquer, Kristell Combe, Christophe Montaurier, Jérôme Salles, Christophe Giraudet, Véronique Patrac, Carla Domingues-Faria, Christelle Guillet, Katie Louche, Yves Boirie, Nahum Sonenberg, Cédric Moro, Stéphane Walrand
SCOPE: In recent years, several studies reported the role of eIF4E-binding proteins (4E-BPs) on the development of diet-induced obesity and insulin resistance. Our aim was to investigate the effect of 4E-BP protein deletion on lipid accumulation and metabolism in skeletal muscle in response to a high fat diet-induced obesity in 4E-BP1/2 DKO mice. METHODS AND RESULTS: Diet-induced obesity engendered increased ectopic accumulation of lipotoxic species in skeletal muscle of 4E-BP1 and 4E-BP2 double-knockout mice (4E-BP1/2 DKO), namely diacylglycerols and ceramides...
May 21, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/28538106/intramuscular-triglyceride-content-precedes-impaired-glucose-metabolism-without-evidence-for-mitochondrial-dysfunction-during-early-development-of-a-diabetic-phenotype
#3
Zachary J Callahan, Michael James Oxendine, Paul J Schaeffer
The incidence of type 2 diabetes is highly correlated with obesity; however, there is a lack of research elucidating the temporal progression. Transgenic FVB/N UCP-dta mice, which develop a diabetic phenotype, and their non-transgenic littermates were fed either a high-fat or normal-chow diet and were studied at 6, 9, 12, 15, 18, 21, and 24 weeks of age in order to test the hypothesis that increased lipid accumulation in skeletal muscle causes mitochondrial dysfunction, leading to the development of insulin resistance...
May 24, 2017: Applied Physiology, Nutrition, and Metabolism, Physiologie Appliquée, Nutrition et Métabolisme
https://www.readbyqxmd.com/read/28527893/chemistry-and-biology-of-reactive-species-with-special-reference-to-the-antioxidative-defence-status-in-pancreatic-%C3%AE-cells
#4
REVIEW
Sigurd Lenzen
BACKGROUND: Diabetes mellitus is a serious metabolic disease. Dysfunction and subsequent loss of the β-cells in the islets of Langerhans through apoptosis ultimately cause a life-threatening insulin deficiency. The underlying reason for the particular vulnerability of the β-cells is an extraordinary sensitivity to the toxicity of reactive oxygen and nitrogen species (ROS and RNS) due to its low antioxidative defense status. SCOPE REVIEW: This review considers the different aspects of the chemistry and biology of the biologically most important reactive species and their chemico-biological interactions in the β-cell toxicity of proinflammatory cytokines in type 1 diabetes and of lipotoxicity in type 2 diabetes development...
May 17, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28526415/lnk-deficiency-aggregates-palmitate-induced-preadipocyte-apoptosis
#5
Jie-Yi Du, Chen-Chen Jin, Guo-Hao Wang, Xiong-Qing Huang, Jian-Ding Cheng, Xue-Jun Wen, Xiao-Miao Zhao, Guan-Lei Wang
LNK (SH2B3) is an intracellular adaptor protein that negatively regulates cellular proliferation or self-renewal of hematopoietic stem cells and some other progenitor cells. LNK is also recognized as a key regulator of insulin resistance and inflammatory responses in several tissues and organs. It is unknown the function of LNK in adipose tissue. We previously demonstrated that type 2 diabetes mellitus (T2DM) mouse model had elevated serum free fatty acids (FFAs) levels and increased preadipocyte apoptosis in visceral fat tissue, showing the occurrence of lipotoxicity...
May 16, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28522407/high-throughput-screening-and-bioinformatic-analysis-to-ascertain-compounds-that-prevent-saturated-fatty-acid-induced-%C3%AE-cell-apoptosis
#6
Seung-Hee Lee, Daniel Cunha, Carlo Piermarocchi, Giovanni Paternostro, Anthony Pinkerton, Laurence Ladriere, Piero Marchetti, Decio L Eizirik, Miriam Cnop, Fred Levine
Pancreatic β-cell lipotoxicity is a central feature of the pathogenesis of type 2 diabetes. To study the mechanism by which fatty acids cause β-cell death and develop novel approaches to prevent it, a high-throughput screen on the β-cell line INS1 was carried out. The cells were exposed to palmitate to induce cell death and compounds that reversed palmitate-induced cytotoxicity were ascertained. Hits from the screen were analyzed by an increasingly more stringent testing funnel, ending with studies on primary human islets treated with palmitate...
May 15, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28522296/oleate-protects-macrophages-from-palmitate-induced-apoptosis-through-the-downregulation-of-cd36-expression
#7
Dong Hee Kim, Yoon Mi Cho, Kyung Hye Lee, Seong-Whan Jeong, Oh-Joo Kwon
In obese patients, free fatty acids ectopically accumulated in non-adipose tissues cause cell death. Saturated fatty acids are more deleterious to non-adipose cells, and supplementation with monounsaturated fatty acids has been proposed to rescue cells from saturated fatty acid-induced cytotoxicity; however, the mechanisms are not well understood. To understand the cytoprotective role of monounsaturated fatty acids in lipotoxic cell death of macrophages, we investigated the antagonizing effect of oleate and the underlying mechanisms in palmitate-treated RAW264...
May 15, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28520897/alpha-linolenic-acid-protects-the-developmental-capacity-of-bovine-cumulus-oocyte-complexes-matured-under-lipotoxic-conditions-in-vitro
#8
W F A Marei, J De Bie, O Mohey-Elsaeed, E Wydooghe, P E J Bols, J L M R Leroy
Elevated concentrations of free fatty acids (FFAs), predominantly palmitic, stearic and oleic acids (PSO), exert detrimental effects on oocyte developmental competence. This study examined the effects of omega-3 alpha-linolenic acid (ALA) during in vitro oocyte maturation (IVM) in the presence of PSO on subsequent embryo development and quality, and the cellular mechanisms that might be involved. Bovine cumulus oocyte complexes (COCs) were supplemented during IVM with ALA (50 μM), PSO (425 μM), or PSO+ALA...
May 18, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/28520810/long-chain-saturated-and-unsaturated-fatty-acids-exert-opposing-effects-on-viability-and-function-of-glp-1-producing-cells-mechanisms-of-lipotoxicity
#9
Ketan Thombare, Stelia Ntika, Xuan Wang, Camilla Krizhanovskii
BACKGROUND AND AIM: Fatty acids acutely stimulate GLP-1 secretion from L-cells in vivo. However, a high fat diet has been shown to reduce the density of L-cells in the mouse intestine and a positive correlation has been indicated between L-cell number and GLP-1 secretion. Thus, the mechanism of fatty acid-stimulated GLP-1 secretion, potential effects of long-term exposure to elevated levels of different fatty acid species, and underlying mechanisms are not fully understood. In the present study, we sought to determine how long-term exposure to saturated (16:0) and unsaturated (18:1) fatty acids, by direct effects on GLP-1-producing cells, alter function and viability, and the underlying mechanisms...
2017: PloS One
https://www.readbyqxmd.com/read/28515456/metabolomic-analysis-shows-differential-hepatic-effects-of-t2-and-t3-in-rats-after-short-term-feeding-with-high-fat-diet
#10
Liliana F Iannucci, Federica Cioffi, Rosalba Senese, Fernando Goglia, Antonia Lanni, Paul M Yen, Rohit A Sinha
Nonalcoholic fatty liver disease (NAFLD) is a major health problem worldwide, and is often associated with lipotoxic injury, defective mitochondrial function, and insulin resistance. Thyroid hormones (THs) are important regulators of hepatic lipid metabolism. Among the THs, diiodothyronine (T2) and triiodothyronine (T3) have shown promising results in lowering hepatic fat content in various models of NAFLD. In this study, we used a targeted metabolomics approach to investigate the differential effects of T2 and T3 on the early metabolic adaptation in the livers of rats fed high fat diet (HFD), a period when hepatosteatosis is reversible...
May 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28504910/fermented-moringa-oleifera-decreases-hepatic-adiposity-and-ameliorates-glucose-intolerance-in-high-fat-diet-induced-obese-mice
#11
Hyunchae Joung, Bobae Kim, Hyunjoon Park, Kyuyeon Lee, Hee-Hoon Kim, Ho-Cheol Sim, Hyun-Jin Do, Chang-Kee Hyun, Myoung-Sool Do
Metabolic diseases, such as glucose intolerance and nonalcoholic fatty-liver disease (NAFLD), are primary risk factors for life-threatening conditions such as diabetes, heart attack, stroke, and hepatic cancer. Extracts from the tropical tree Moringa oleifera show antidiabetic, antioxidant, anti-inflammatory, and anticancer effects. Fermentation can further improve the safety and nutritional value of certain foods. We investigated the efficacy of fermented M. oleifera extract (FM) against high-fat diet (HFD)-induced glucose intolerance and hepatic lipid accumulation and investigated the underlying mechanisms by analyzing expression of proteins and genes involved in glucose and lipid regulation...
May 2017: Journal of Medicinal Food
https://www.readbyqxmd.com/read/28500736/high-density-lipoprotein-hdl-reverses-palmitic-acid-induced-energy-metabolism-imbalance-by-switching-cd36-and-glut4-signaling-pathways-in-cardiomyocyte
#12
Su-Ying Wen, Bharath Kumar Velmurugan, Cecilia Hsuan Day, Chia-Yao Shen, Li-Chin Chun, Yi-Chieh Tsai, Yueh-Min Lin, Ray-Jade Chen, Chia-Hua Kuo, Chih-Yang Huang
In our previous study palmitic acid (PA) induced lipotoxicity and switches energy metabolism from CD36 to GLUT4 in H9c2 cells. Low level of high density lipoprotein (HDL) is an independent risk factor for cardiac hypertrophy. Therefore we in the present study investigated whether HDL can reverse PA induced lipotoxicity in H9c2 cardiomyoblast cells. In this study, we treated H9c2 cells with PA to create a hyperlipidemia model in vitro and analyzed for CD36 and GLUT4 metabolic pathway proteins. CD36 metabolic pathway proteins (phospho-AMPK, SIRT1, PGC1α, PPARα, CPT1β and CD36) were decreased by high PA (150 and 200 µg/µL) concentration...
May 13, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28490610/mechanisms-of-insulin-resistance-in-primary-and-secondary-non-alcoholic-fatty-liver
#13
Tomas Jelenik, Kirti Kaul, Gilles Séquaris, Ulrich Flögel, Esther Phielix, Jörg Kotzka, Birgit Knebel, Pia Fahlbusch, Tina Hörbelt, Stefan Lehr, Anna Lena Reinbeck, Dirk Müller-Wieland, Irene Esposito, Gerald I Shulman, Julia Szendroedi, Michael Roden
Non-alcoholic fatty liver disease (NAFLD) is associated with hepatic insulin resistance and may result primarily from increased hepatic de novo lipogenesis (PRIM) or secondarily from adipose-tissue lipolysis (SEC). We studied mice with hepatocyte- or adipocyte-specific sterol regulatory-element binding protein-1c (SREBP-1c) overexpression as models of PRIM and SEC. PRIM mice featured increased lipogenic gene expression in liver and adipose tissue. Their selective, liver-specific insulin resistance was associated with increased C18:1-diacylglycerol (DAG) content and protein kinase C (PKC)ε translocation...
May 10, 2017: Diabetes
https://www.readbyqxmd.com/read/28486193/wogonin-mitigates-nonalcoholic-fatty-liver-disease-via-enhancing-ppar%C3%AE-adipor2-in-vivo-and-in-vitro
#14
Jing Chen, Jie Liu, Ye Wang, Xuemei Hu, Feng Zhou, Yimeng Hu, Yin Yuan, Yancheng Xu
Wogonin has been reported to attenuate hyperglycemia in diabetic mice via anti-adipogenic effect on adipocytes. The potential therapeutic role of wogonin in nonalcoholic fatty liver disease (NAFLD) remains obscure. The aim of the present study was to explore the protective effect of wogonin on NAFLD mice and cultured NCTC 1469 cells exposed to palmitate. Wogonin supplementation significantly improved metabolic parameters in NAFLD mice, including body weight, blood glucose, insulin resistance, adiponectin, blood lipids, aminotransferases and hepatic histopathology...
May 6, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28476623/syringin-attenuates-insulin-resistance-via-adiponectin-mediated-suppression-of-low-grade-chronic-inflammation-and-er-stress-in-high-fat-diet-fed-mice
#15
Bobae Kim, Min-Seok Kim, Chang-Kee Hyun
In the treatment of type 2 diabetes, improvements in glucose control are often linked to side effects such as weight gain and altered lipid metabolism, increasing the risk of cardiovascular disease. It is therefore important to develop antidiabetic drugs that exert beneficial effects on insulin sensitivity and lipid metabolism at the same time. Here we demonstrate that syringin, a naturally occurring glucoside, improves glucose tolerance without increased weight gain in high-fat diet-induced obese mice. Syringin augmented insulin-stimulated Akt phosphorylation in skeletal muscle, epididymal adipose tissue (EAT), and the liver, showing an insulin-sensitizing activity...
June 17, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28473059/nicotinamide-protects-hepatocytes-against-palmitate-induced-lipotoxicity-via-sirt1-dependent-autophagy-induction
#16
Chen Shen, Xiaobing Dou, Yue Ma, Wang Ma, Songtao Li, Zhenyuan Song
Lipotoxicity induced by saturated fatty acids (SFAs) plays a pathological role in the development of non-alcoholic fatty liver disease (NAFLD); however, the exact mechanism remains to be clearly elucidated. Palmitate is the most abundant SFA in the circulation and major lipotoxic inducer. Accumulating evidence supports that autophagy induction is protective against palmitate-induced cell death in a variety of cell types, including hepatocytes. Nicotinamide is the amide form of nicotinic acid (vitamin B3, Niacin) and a dietary supplementation as a source of vitamin B3...
April 2017: Nutrition Research
https://www.readbyqxmd.com/read/28468951/insulin-resistance-promotes-lysyl-oxidase-like-2induction-and-fibrosis-accumulation-in-nonalcoholic-fatty-liver-disease
#17
Paola Dongiovanni, Marica Meroni, Guido Alessandro Baselli, Giulia Alessandra Bassani, Raffaela Rametta, Alessandro Pietrelli, Marco Maggioni, Federica Facciotti, Valentina Trunzo, Sara Badiali, Silvia Fargion, Stefano Gatti, Luca Vittorio Carlo Valenti
Background & Aims: In patients with nonalcoholic fatty liver disease (NAFLD), insulin resistance (IR) associates with fibrosis progression independently of hepatic inflammation, but the mechanisms are still unclear. Methods : We modeled the independent contribution of inflammation (steatohepatitis: NASH) by exploiting the methionine-choline deficient (MCD) diet, and that of IR by insulin receptor haploinsufficiency (InsR+/-), in the pathogenesis of liver fibrosis in C57Bl/6 mice. We confirmed study findings in 96 patients with NAFLD...
May 3, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28465791/insulin-mimetic-compound-hexaquis-benzylammonium-decavanadate-is-antilipolytic-in-human-fat-cells
#18
Christian Carpéné, Silvia Garcia-Vicente, Marta Serrano, Luc Marti, Chloé Belles, Miriam Royo, Jean Galitzky, Antonio Zorzano, Xavier Testar
AIM: To assess in rodent and human adipocytes the antilipolytic capacity of hexaquis(benzylammonium) decavanadate (B6V10), previously shown to exert antidiabetic effects in rodent models, such as lowering free fatty acids (FFA) and glucose circulating levels. METHODS: Adipose tissue (AT) samples were obtained after informed consent from overweight women undergoing plastic surgery. Comparison of the effects of B6V10 and reference antilipolytic agents (insulin, benzylamine, vanadate) on the lipolytic activity was performed on adipocytes freshly isolated from rat, mouse and human AT...
April 15, 2017: World Journal of Diabetes
https://www.readbyqxmd.com/read/28461456/elovl6-deficiency-improves-glycemic-control-in-diabetic-db-db-mice-by-expanding-%C3%AE-cell-mass-and-increasing-insulin-secretory-capacity
#19
Hui Zhao, Takashi Matsuzaka, Yuta Nakano, Kaori Motomura, Nie Tang, Tomotaka Yokoo, Yuka Okajima, Song-Iee Han, Yoshinori Takeuchi, Yuichi Aita, Hitoshi Iwasaki, Shigeru Yatoh, Hiroaki Suzuki, Motohiro Sekiya, Naoya Yahagi, Yoshimi Nakagawa, Hirohito Sone, Nobuhiro Yamada, Hitoshi Shimano
Dysfunctional fatty acid (FA) metabolism plays an important role in the pathogenesis of β-cell dysfunction and loss of β-cell mass in type 2 diabetes (T2D). Elovl6 is a microsomal enzyme that is responsible for converting C16 saturated and monounsaturated FAs into C18 species. We previously showed that Elovl6 played a critical role in the development of obesity-induced insulin resistance by modifying FA composition. To further define its role in T2D development, we assessed the effects of Elovl6 deletion in leptin receptor-deficient C57BL/KsJ db/db mice, a model of T2D...
May 1, 2017: Diabetes
https://www.readbyqxmd.com/read/28456145/autophagy-plays-beneficial-effect-on-diabetic-encephalopathy-in-type-2-diabetes-studies-in-vivo-and-in-vitro
#20
Yu-Hong Jing, Lang Zhang, Li-Ping Gao, Chu-Chu Qi, Dan-Dan Lv, Yan-Feng Song, Jie Yin, De-Gui Wang
OBJECTIVES: The hypothalamus regulates metabolism and feeding behavior by perceiving the levels of peripheral insulin. However, little is known about the hypothalamic changes after aberrant metabolism. In this study, we investigated the changes of insulin and autophagy relevant signals of hypothalamus under diabetes mellitus. METHODS: C57B/L mice were injected with low-dose streptozotocin (STZ) and fed with high-fat diet to induce type 2 diabetes mellitus. In vitro, PC12 cells were treated with oleic acid to mimic lipotoxicity...
February 15, 2017: Neuro Endocrinology Letters
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