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https://www.readbyqxmd.com/read/29789539/proteasomal-degradation-of-the-histone-acetyl-transferase-p300-contributes-to-beta-cell-injury-in-a-diabetes-environment
#1
Lucie Ruiz, Tatyana Gurlo, Magalie A Ravier, Anne Wojtusciszyn, Julia Mathieu, Matthew R Brown, Christophe Broca, Gyslaine Bertrand, Peter C Butler, Aleksey V Matveyenko, Stéphane Dalle, Safia Costes
In type 2 diabetes, amyloid oligomers, chronic hyperglycemia, lipotoxicity, and pro-inflammatory cytokines are detrimental to beta-cells, causing apoptosis and impaired insulin secretion. The histone acetyl transferase p300, involved in remodeling of chromatin structure by epigenetic mechanisms, is a key ubiquitous activator of the transcriptional machinery. In this study, we report that loss of p300 acetyl transferase activity and expression leads to beta-cell apoptosis, and most importantly, that stress situations known to be associated with diabetes alter p300 levels and functional integrity...
May 22, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29783189/sall2-knockdown-exacerbates-palmitic-acid-induced-dysfunction-and-apoptosis-of-pancreatic-nit-1-beta-cells
#2
Ye Wang, Jie Liu, Zheng Liu, Jing Chen, Xuemei Hu, Yimeng Hu, Yin Yuan, Guijun Wu, Zhe Dai, Yancheng Xu
Spalt-like (Sall) proteins are a class of transcription factors. The role of Sall2 in beta cells remain poorly understood. Here, we aimed to explore whether Sall2 involved in lipotoxicity-mediated dysfunction and apoptosis in pancreatic NIT-1 beta cells. Our results showed that high concentrations of palmitic acid (PA) led to impaired cell viability and decreased Sall2 expression in NIT-1 cells. Knocking down of Sall2 in NIT-1 cells resulted in increased sensitivity to lipotoxicity and caused higher rates of cell apoptosis following PA treatment...
May 18, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29772998/partially-purified-aqueous-fraction-of-desmodium-gyrans-dc-improves-reverse-cholesterol-transport-and-lipoprotein-metabolism-in-wistar-rats-fed-with-high-fat-diet
#3
M S Indu, Jose Padikkala, Achuthan C Raghavamenon
Apart from the conventional hypolipidemic therapy, plaque regression through enhanced reverse cholesterol transport (RCT) has emerged as novel approach in atherosclerotic drug development. High-density lipoprotein (HDL) mimetics as well as agents that augment the functional HDL and RCT pathways are under intense exploration. Desmodium gyrans (Fabacea) has been shown to have hypolipidemic efficacy, with an HDL-enhancing property. In this study, a chromatographically purified active fraction of D. gyrans (DGMAF) significantly decreased the serum and lipid profiles as well as lipotoxicity in liver in Wistar rats fed with high-fat diet (HFD)...
2018: Journal of Environmental Pathology, Toxicology and Oncology
https://www.readbyqxmd.com/read/29759974/the-ceramide-transporter-cert-is-involved-in-muscle-insulin-signaling-defects-under-lipotoxic-conditions
#4
Cécile L Bandet, Rana Mahfouz, Julien Véret, Athanassia Sotiropoulos, Maxime Poirier, Paola Giussani, Mélanie Campana, Erwann Philippe, Agnieszka Blachnio-Zabielska, Raphaëlle Ballaire, Xavier Le Liepvre, Olivier Bourron, Dušan Berkeš, Jan Górski, Pascal Ferré, Hervé Le Stunff, Fabienne Foufelle, Eric Hajduch
One main mechanism of insulin resistance (IR), a key feature of type-2 diabetes, is the accumulation of saturated fatty acids (FA) in muscles of obese and type-2 diabetic patients. Understanding the mechanism underlying lipid-induced IR is therefore a crucial challenge. Saturated FA are metabolized into lipid-derivatives called ceramides and their accumulation plays a central role in the development of muscle IR. Ceramides are produced in the endoplasmic reticulum (ER) and transported to the Golgi through a transporter called CERT, where they are converted into different sphingolipid species...
May 14, 2018: Diabetes
https://www.readbyqxmd.com/read/29747667/protective-effect-of-grape-seed-and-skin-extract-against-high-fat-diet-induced-dyshomeostasis-of-energetic-metabolism-in-rat-lung
#5
Mohamed El Ayed, Safwen Kadri, Maha Mabrouk, Ezzedine Aouani, Salem Elkahoui
BACKGROUND: Obesity is currently one of the major epidemics of this millennium and affects poeples throughout the world. It causes multiple systemic complications as it significantly interferes with respiratory function. OBJECTIVE: We aimed in the present work to study the effect of high fat diet (HFD) on lung oxidative stress and energy metabolism alterations, as well as the putative protection afforded by grape seed and skin extract (GSSE). METHODS: We started by characterizing the GSSE and its composition using gas chromatography coupled to mass spectrometry (GC-MS)...
May 10, 2018: Lipids in Health and Disease
https://www.readbyqxmd.com/read/29740166/triggering-and-resolution-of-inflammation-in-nash
#6
REVIEW
Susanne Schuster, Daniel Cabrera, Marco Arrese, Ariel E Feldstein
Nonalcoholic steatohepatitis (NASH) is considered the progressive form of nonalcoholic fatty liver disease (NAFLD) and is characterized by liver steatosis, inflammation, hepatocellular injury and different degrees of fibrosis. A central issue in this field relates to the identification of those factors that trigger inflammation, thus fuelling the transition from nonalcoholic fatty liver to NASH. These triggers of liver inflammation might have their origins outside the liver (such as in adipose tissue or the gut) as well as inside the organ (for instance, lipotoxicity, innate immune responses, cell death pathways, mitochondrial dysfunction and endoplasmic reticulum stress), both of which contribute to NASH development...
May 8, 2018: Nature Reviews. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/29738801/-p-clphse-2-stabilizes-metabolic-function-in-a-rat-model-of-neuroendocrine-obesity-induced-by-monosodium-glutamate
#7
Caroline B Quines, Suzan G Rosa, Daniela Velasquez, Vinicius C Prado, José S S Neto, Cristina W Nogueira
Obesity is a chronic and complex medical condition characterized by excessive fat accumulation and its complications include metabolic syndrome, diabetes and chronic inflammation. The aim of this study was to expand the knowledge about p-chloro-diphenyl diselenide (p-ClPhSe)2 effects on enzymes and proteins involved in the metabolism of lipids and carbohydrates in a model of neuroendocrine obesity induced by MSG. Male Wistar rats were treated during the first ten postnatal days with MSG (4 g/kg, s.c.) and received (p-ClPhSe)2 (10 mg/kg, i...
May 5, 2018: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/29733984/long-chain-metabolites-of-vitamin-e-interference-with-lipotoxicity-via-lipid-droplet-associated-protein-plin2
#8
Lisa Schmölz, Martin Schubert, Jasmin Kirschner, Stefan Kluge, Francesco Galli, Marc Birringer, Maria Wallert, Stefan Lorkowski
The long-chain metabolites of vitamin E (LCM) emerge as a new class of regulatory metabolites and have been considered as the active compounds formed during vitamin E metabolism. The bioactivity of the LCM is comparable to the already established role of other fat-soluble vitamins. The biological modes of action of the LCM are far from being unraveled, but first insights pointed to distinct effects and suggested a specific receptor, which in turn lead to the aforementioned hypothesis. Here, a new facet on the interaction of LCM with foam cell formation of THP-1 macrophages is presented...
May 4, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29733848/polyacetylene-glycoside-attenuates-ischemic-kidney-injury-by-co-inhibiting-inflammation-mitochondria-dysfunction-and-lipotoxicity
#9
Yijie Zhou, Dan Du, Shuyun Liu, Meng Zhao, Yujia Yuan, Lan Li, Younan Chen, Yanrong Lu, Jingqiu Cheng, Jingping Liu
AIMS: Ischemic acute kidney injury (AKI) is a serious clinical problem and no efficient therapeutics is available in clinic now. Natural polyacetylene glycosides (PGAs) had shown antioxidant and anti-inflammatory properties, but their effects on kidney injury have not been evaluated. This study aimed to investigate the protective effect of PGA on ischemic kidney injury in renal tubular epithelial cells (TECs) and mice. MAIN METHODS: Hypoxic HK-2 cells and renal ischemia/reperfusion injury (IRI) mice were treated with PGA from Coreopsis tinctoria, and the cell viability, renal function, apoptosis, inflammation, mitochondrial injury, lipids metabolism were analyzed...
May 4, 2018: Life Sciences
https://www.readbyqxmd.com/read/29729479/palmitate-lipotoxicity-in-enteric-glial-cells-lipid-remodeling-and-mitochondrial-ros-are-responsible-for-cyt-c-release-outside-mitochondria
#10
Lara Macchioni, Maya Petricciuolo, Magdalena Davidescu, Katia Fettucciari, Paolo Scarpelli, Rita Vitale, Leonardo Gatticchi, Pierluigi Orvietani, Andrea Marchegiani, Pierfrancesco Marconi, Gabrio Bassotti, Angela Corcelli, Lanfranco Corazzi
Enteric glial cells (EGCs) are components of the enteric nervous system, an organized structure that controls gut functions. EGCs may be vulnerable to different agents, such as bacterial infections that could alter the intestinal epithelial barrier, allowing bacterial toxins and/or other agents possessing intrinsic toxic effect to access cells. Palmitate, known to exhibit lipotoxicity, is released in the gut during the digestion process. In this study, we investigated the lipotoxic effect of palmitate in cultured EGCs, with particular emphasis on palmitate-dependent intracellular lipid remodeling...
May 2, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29718175/lipotoxicty-in-yeast-a-focus-on-plasma-membrane-signalling-and-membrane-contact-sites
#11
Patrick Rockenfeller, Campbell W Gourlay
Lipotoxicity is a pathophysiological process triggered by lipid overload. In metazoans, lipotoxicity is characterised by the ectopic deposition of lipids on organs other than adipose tissue. This leads to organ dysfunction, cell death, and is intimately linked to lipid-associated diseases such as cardiac dysfunction, atherosclerosis, stroke, hepatosteatosis, cancer and the metabolic syndrome. The molecules involved in eliciting lipotoxicity include FAs and their acyl-CoA derivatives, triacylglycerol (TG), diacylglycerol (DG), ceramides, acyl-carnitines and phospholipids...
June 1, 2018: FEMS Yeast Research
https://www.readbyqxmd.com/read/29717278/role-of-obesity-in-the-release-of-extracellular-nucleosomes-in-acute-pancreatitis-a-clinical-and-experimental-study
#12
Salvador Pérez, Isabela Finamor, Pablo Martí-Andrés, Javier Pereda, Ana Campos, Rosário Domingues, Fawaz Haj, Luis Sabater, Enrique de-Madaria, Juan Sastre
BACKGROUND/OBJECTIVES: A high body mass index increases the risk of severe pancreatitis and associated mortality. Our aims were: (1) To determine whether obesity affects the release of extracellular nucleosomes in patients with pancreatitis; (2) To determine whether pancreatic ascites confers lipotoxicity and triggers the release of extracellular nucleosomes in lean and obese rats. METHODS: DNA and nucleosomes were determined in plasma from patients with mild or moderately severe acute pancreatitis either with normal or high body mass index (BMI)...
May 1, 2018: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/29713145/inhibition-of-ghrelin-o-acyltransferase-attenuated-lipotoxicity-by-inducing-autophagy-via-ampk-mtor-pathway
#13
Shaoren Zhang, Yuqing Mao, Xiaoming Fan
Background: Nonalcoholic fatty liver disease (NAFLD) has been considered the most commonly occurring chronic hepatopathy in the world. Ghrelin o -acyltransferase (GOAT) is an acylation enzyme which has an acylated position 3 serine on ghrelin. Recent investigation revealed that activated autophagy could attenuate liver steatosis. The aim of this study was to explore therapeutic roles that inhibit GOAT exerted in NAFLD, and its potential association with autophagy. Materials and methods: Human LO2 cells were pretreated with siRNA-GOAT to induce liver steatosis using free fatty acids (FFAs)...
2018: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/29709680/liver-master-and-servant-of-serum-proteome
#14
REVIEW
Deniz Kuscuoglu, Sabina Janciauskiene, Karim Hamesch, Johannes Haybaeck, Christian Trautwein, Pavel Strnad
In the endoplasmic reticulum (ER), hepatocytes synthesize the majority of serum proteins and this production is adjusted by complex local and systemic regulatory mechanisms. Accordingly, serum levels of hepatocyte-made proteins constitute important biomarkers that reflect both systemic processes and the status of the liver. For example, C-reactive protein is an established marker of inflammatory reaction, whereas transferrin emerges as a liver stress marker and an attractive mortality predictor. The high protein flow through the ER poses a continuous challenge that is handled by a complex proteostatic network consisting of ER folding machinery, ER stress response, ER-associated degradation and autophagy...
April 27, 2018: Journal of Hepatology
https://www.readbyqxmd.com/read/29709653/oleic-acid-protects-saturated-fatty-acid-mediated-lipotoxicity-in-hepatocytes-and-rat-of-non-alcoholic-steatohepatitis
#15
Xuanming Chen, Linzhao Li, Xiaohong Liu, Ruixi Luo, Guangneng Liao, Lan Li, Jingping Liu, Jingqiu Cheng, Yanrong Lu, Younan Chen
Aim This study aims to demonstrate the protective effects of monounsaturated oleic acid (OA) against saturated palmitic acid (PA) induced cellular lipotoxicity in hepatocytes and rats with non-alcoholic steatohepatitis (NASH). MAIN METHODS: Human hepatoma cell line HepG2 cells and neonatal rat primary hepatocytes were treated with PA or/and OA for 24 h. SD rats were fed with high fat diet (HFD) to induce NASH. From the 16th w, the HFD was full or half replaced by olive oil to observe the protective effects...
April 27, 2018: Life Sciences
https://www.readbyqxmd.com/read/29704577/food-drug-interaction-anabolic-steroids-aggravate-hepatic-lipotoxicity-and-nonalcoholic-fatty-liver-disease-induced-by-trans-fatty-acids
#16
Jamili D B Santos, Andrea A S Mendonça, Rafaela C Sousa, Thaiany G S Silva, Solange M Bigonha, Eliziária C Santos, Reggiani V Gonçalves, Romulo D Novaes
Remains unknown if dietary lipids and anabolic steroids (AS) can interact to modify energy metabolism, hepatic structure and function. We investigated the impact of AS on gene expression, lipid profile, redox status and the development of nonalcoholic fatty liver disease (NAFLD) in mice treated with a diet rich in trans fatty acids. Seventy-two C57BL/6 mice were equally randomized into six groups and treated with a standard diet (SD) or high-fat diet (HFD) alone or combined with testosterone cypionate (10 or 20 mg/kg) for 12 weeks...
April 25, 2018: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/29695452/ppar%C3%AE-agonist-pioglitazone-reverses-pulmonary-hypertension-and-prevents-right-heart-failure-via-fatty-acid-oxidation
#17
Ekaterina Legchenko, Philippe Chouvarine, Paul Borchert, Angeles Fernandez-Gonzalez, Erin Snay, Martin Meier, Lavinia Maegel, S Alex Mitsialis, Eva A Rog-Zielinska, Stella Kourembanas, Danny Jonigk, Georg Hansmann
Right ventricular (RV) heart failure is the leading cause of death in pulmonary arterial hypertension (PAH). Peroxisome proliferator-activated receptor γ (PPARγ) acts as a vasoprotective metabolic regulator in smooth muscle and endothelial cells; however, its role in the heart is unclear. We report that deletion of PPARγ in cardiomyocytes leads to biventricular systolic dysfunction and intramyocellular lipid accumulation in mice. In the SU5416/hypoxia (SuHx) rat model, oral treatment with the PPARγ agonist pioglitazone completely reverses severe PAH and vascular remodeling and prevents RV failure...
April 25, 2018: Science Translational Medicine
https://www.readbyqxmd.com/read/29688808/dna-methylation-and-the-potential-role-of-demethylating-agents-in-prevention-of-progressive-chronic-kidney-disease
#18
Benjamin P Larkin, Sarah J Glastras, Hui Chen, Carol A Pollock, Sonia Saad
Chronic kidney disease (CKD) is a global epidemic, and its major risk factors include obesity and type 2 diabetes. Obesity not only promotes metabolic dysregulation and the development of diabetic kidney disease but also may independently lead to CKD by a variety of mechanisms, including endocrine and metabolic dysfunction, inflammation, oxidative stress, altered renal hemodynamics, and lipotoxicity. Deleterious renal effects of obesity can also be transmitted from one generation to the next, and it is increasingly recognized that offspring of obese mothers are predisposed to CKD...
April 24, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29684344/er-stress-attenuation-by-aloe-derived-polysaccharides-in-the-protection-of-pancreatic-%C3%AE-cells-from-free-fatty-acid-induced-lipotoxicity
#19
Kisoo Kim, Min Hwa Chung, Soyoung Park, Jimin Cha, Jin Hong Baek, Shin-Young Lee, Sang-Yun Choi
Insulin resistance, a pathophysiology of type 2 diabetes, is associated with obesity. Lipotoxicity in obesity leads to the dysfunction and death of pancreatic β-cells and inadequate insulin production, thereby aggravating type 2 diabetes. The present study was conducted to determine the effect of Aloe vera polysaccharides (APs) as an anti-hyperglycemic agent and their mechanisms of action. Gel polysaccharides from Aloe extracts were separated using ultrafiltration devices with molecular weight-cutoff membranes, and the protective effect of APs on pancreatic β-cells in response to free fatty acids (FFAs) was determined...
June 7, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29679627/diabetes-and-cancer-pathophysiological-fundamentals-of-a-dangerous-affair
#20
REVIEW
Angelo Cignarelli, Valentina Annamaria Genchi, Irene Caruso, Annalisa Natalicchio, Sebastio Perrini, Luigi Laviola, Francesco Giorgino
Diabetes and cancer are worldwide chronic diseases with a major impact on the quality and expectancy of life. Metabolic abnormalities observed during the onset and progression of diabetes may have a critical role on the initiation and progression of carcinogenesis. To date, there are no conclusive data on the mechanisms underlying the relationship between diabetes and any type of human cancer. However, recent evidence suggests that both hyperglycemia and hyperinsulinemia in diabetes could elicit cell damage responses, such as glucotoxicity, lipotoxicity and oxidative stress, which participate in the cell transformation process raising the risk of cancer development...
April 19, 2018: Diabetes Research and Clinical Practice
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