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https://www.readbyqxmd.com/read/28102311/plin2-is-a-key-regulator-of-the-unfolded-protein-response-and-endoplasmic-reticulum-stress-resolution-in-pancreatic-%C3%AE-cells
#1
Elaine Chen, Tsung Huang Tsai, Lan Li, Pradip Saha, Lawrence Chan, Benny Hung-Junn Chang
Progressive pancreatic β cell failure underlies the transition of impaired glucose tolerance to overt diabetes; endoplasmic reticulum (ER) stress expedites β cell failure in this situation. ER stress can be elicited by lipotoxicity and an increased demand for insulin in diabetes. We previously reported that the lipid droplet protein perilipin 2 (PLIN2) modulates lipid homeostasis in the liver. Here, we show that PLIN2 modulates the unfolded protein response (UPR) and ER stress in pancreatic β cells. PLIN2 expression goes up when β cells are exposed to a lipid load or to chemical ER stress inducers...
January 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28094778/adipocyte-fatty-acid-binding-protein-potentiates-toxic-lipids-induced-endoplasmic-reticulum-stress-in-macrophages-via-inhibition-of-janus-kinase-2-dependent-autophagy
#2
Ruby L C Hoo, Lingling Shu, Kenneth K Y Cheng, Xiaoping Wu, Boya Liao, Donghai Wu, Zhiguang Zhou, Aimin Xu
Lipotoxicity is implicated in the pathogenesis of obesity-related inflammatory complications by promoting macrophage infiltration and activation. Endoplasmic reticulum (ER) stress and adipocyte fatty acid binding protein (A-FABP) play key roles in obesity and mediate inflammatory activity through similar signaling pathways. However, little is known about their interplay in lipid-induced inflammatory responses. Here, we showed that prolonged treatment of palmitic acid (PA) increased ER stress and expression of A-FABP, which was accompanied by reduced autophagic flux in macrophages...
January 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28088331/eicosapentaenoic-acid-ameliorates-palmitate-induced-lipotoxicity-via-the-amp-kinase-dynamin-related-protein-1-signaling-pathway-in-differentiated-h9c2-myocytes
#3
Atsushi Sakamoto, Masao Saotome, Prottoy Hasan, Terumori Satoh, Hayato Ohtani, Tsuyoshi Urushida, Hideki Katoh, Hiroshi Satoh, Hideharu Hayashi
BACKGROUND: Emerging evidence suggested the preferable effects of eicosapentaenoic acid (EPA; n-3 polyunsaturated fatty acid) against cardiac lipotoxicity, which worsens cardiac function by means of excessive serum free fatty acids due to chronic adrenergic stimulation under heart failure. Nonetheless, the precise molecular mechanisms remain elusive. In this study, we focused on dynamin-related protein-1 (Drp1) as a possible modulator of the EPA-mediated cardiac protection against cardiac lipotoxicity, and investigated the causal relation between AMP-activated protein kinase (AMPK) and Drp1...
January 11, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28087695/novel-interconnections-in-lipid-metabolism-revealed-by-overexpression-of-sphingomyelin-synthase-1
#4
Gergana M Deevska, Patrick P Dotson, Alexander A Karakashian, Giorgis Isaac, Mark Wrona, Samuel B Kelly, Alfred H Merrill, Mariana N Nikolova-Karakashian
This study investigates the consequences of elevating sphingomyelin synthase 1 (SMS1) activity, which generates the main mammalian sphingolipid, sphingomyelin. HepG2 cells stably transfected with SMS1 (HepG2-SMS1), exhibit elevated enzyme activity in vitro and increased sphingomyelin content (mainly C22:0- and C24:0-sphingomyelin), but lower hexosylceramide (Hex-Cer) levels. HepG2-SMS1 cells have less triacylglycerols than controls but similar diacylglycerol acyltransferase activity, triacylglycerol secretion, and mitochondrial function...
January 13, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28086863/exercise-mediated-protection-of-diabetic-heart-through-modulation-of-microrna-mediated-molecular-pathways
#5
REVIEW
Jason Kar Sheng Lew, James T Pearson, Daryl O Schwenke, Rajesh Katare
Hyperglycaemia, hypertension, dyslipidemia and insulin resistance collectively impact on the myocardium of people with diabetes, triggering molecular, structural and myocardial abnormalities. These have been suggested to aggravate oxidative stress, systemic inflammation, myocardial lipotoxicity and impaired myocardial substrate utilization. As a consequence, this leads to the development of a spectrum of cardiovascular diseases, which may include but not limited to coronary endothelial dysfunction, and left ventricular remodelling and dysfunction...
January 13, 2017: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/28076832/dietary-supplementation-of-grape-seed-and-skin-flour-mitigates-brain-oxidative-damage-induced-by-a-high-fat-diet-in-rat-gender-dependency
#6
Kamel Charradi, Mohamed Mahmoudi, Takwa Bedhiafi, Safwen Kadri, Salem Elkahoui, Ferid Limam, Ezzedine Aouani
It is unknown whether gender has an impact on brain injury in obesity, and, if so, whether treatment with grape seed and skin flour could exert a protective effect. Both male and female rats were fed a standard diet (SD) or a high fat diet (HFD) during eight weeks and treated with high dosage grape seed and skin flour (GSSF). Fat-induced oxidative stress was evaluated into the brain with a special emphasis on transition metals determination. HFD induced male-cholesterol overload (+78.12%) and an oxidative stress status characterized by increased lipoperoxidation (+68...
January 8, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28069865/interleukin-22-restored-mitochondrial-damage-and-impaired-glucose-stimulated-insulin-secretion-through-down-regulation-of-uncoupling-protein-2-in-ins-1-cells
#7
Minling Hu, Hanxiao Lin, Li Yang, Yanzhen Cheng, Hua Zhang
Defective glucose-stimulated insulin secretion (GSIS) induced by chronic exposure to fatty acids is a hallmark of type 2 diabetes (T2D). Interleukin-22 (IL-22) has been shown to exert beneficial effects on insulin secretion and to protect pancreatic β-cells from stress. Moreover, uncoupling protein-2 (UCP-2) plays a central role in the regulation of GSIS and β-cell dysfunction, whereas the role of UCP-2 in IL-22-enhanced glycemic control under conditions of lipotoxicity remains unclear. In this present study, we investigated the effects of IL-22 on rat insulin-secreting cells (INS-1 cells) and the mechanisms that underlie IL-22 and lipotoxicity-impaired GSIS in vitro...
January 7, 2017: Journal of Biochemistry
https://www.readbyqxmd.com/read/28069524/atg14-facilitated-lipophagy-in-cancer-cells-induce-er-stress-mediated-mitoptosis-through-a-ros-dependent-pathway
#8
Subhadip Mukhopadhyay, Isabel R Schlaepfer, Bryan C Bergman, Prashanta Kumar Panda, Prakash Priyadarshi Praharaj, Prajna Paramita Naik, Rajesh Agarwal, Sujit Kumar Bhutia
Understanding the dynamics of autophagy and apoptosis crosstalk in cancer progression remains a challenging task. Here, we reported how the autophagy protein ATG14 induces lipophagy-mediated mitochondrial apoptosis. The overexpression of ATG14 in HeLa cells inhibited cell viability and increased mitochondrial apoptosis and endoplasmic reticulum (ER) stress. Furthermore, inhibition of this ATG14-induced autophagy promoted apoptosis. ATG14 overexpression resulted in the accumulation of stearic acid and oleic acid free fatty acids (FFA), with a concomitant decrease in the number of lipid droplets...
January 6, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28067231/multiomics-reveal-non-alcoholic-fatty-liver-disease-in-rats-following-chronic-exposure-to-an-ultra-low-dose-of-roundup-herbicide
#9
Robin Mesnage, George Renney, Gilles-Eric Séralini, Malcolm Ward, Michael N Antoniou
The impairment of liver function by low environmentally relevant doses of glyphosate-based herbicides (GBH) is still a debatable and unresolved matter. Previously we have shown that rats administered for 2 years with 0.1 ppb (50 ng/L glyphosate equivalent dilution; 4 ng/kg body weight/day daily intake) of a Roundup GBH formulation showed signs of enhanced liver injury as indicated by anatomorphological, blood/urine biochemical changes and transcriptome profiling. Here we present a multiomic study combining metabolome and proteome liver analyses to obtain further insight into the Roundup-induced pathology...
January 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28062415/cardiomyocyte-specific-ablation-of-cd36-accelerates-the-progression-from-compensated-cardiac-hypertrophy-to-heart-failure
#10
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/28056419/chamomile-matricaria-recutita-l-decoction-extract-inhibits-in-vitro-intestinal-glucose-absorption-and-attenuates-high-fat-diet-induced-lipotoxicity-and-oxidative-stress
#11
Mohamed-Amine Jabri, Mohsen Sakly, Lamjed Marzouki, Hichem Sebai
The present study aimed to investigate the inhibitory effect of chamomile decoction extract (CDE) on intestinal glucose absorption as well as its protective role against high fat diet (HFD)-induced obesity and lipotoxicity in rats. We used the Ussing chamber system to investigate the effect of CDE on intestinal transport of glucose. Male Wistar rats were fed HFD for six weeks to provoke obesity. CDE (100mg/kg, b.w. p.o.) has been per orally administered to HFD fed rats. Ex vivo, we found that CDE significantly and dose-dependently increased intestinal absorption of glucose...
January 2, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28052965/the-sglt2-inhibitor-dapagliflozin-prevents-cardiomyopathy-in-a-diabetic-lipodystrophic-mouse-model
#12
Michael Joubert, Benoît Jagu, David Montaigne, Xavier Marechal, Angela Tesse, Audrey Ayer, Lucile Dollet, Cédric Le May, Gilles Toumaniantz, Alain Manrique, Flavien Charpentier, Bart Staels, Jocelyne Magré, Bertand Cariou, Xavier Prieur
Type 2 diabetes mellitus (T2DM) is a well-recognized independent risk factor for heart failure (HF). T2DM is associated with altered cardiac energy metabolism, leading to ectopic lipid accumulation and glucose overload, the exact contribution of these two parameters remaining unclear. To provide new insight into the mechanism driving the development of diabetic cardiomyopathy, we studied a unique model of T2DM: lipodystrophic Bscl2(-/-) (seipin knockout (SKO)) mice. Echocardiography and cardiac magnetic resonance imaging revealed hypertrophic cardiomyopathy with left ventricular dysfunction in SKO mice and these two abnormalities were strongly correlated with hyperglycemia...
January 4, 2017: Diabetes
https://www.readbyqxmd.com/read/28039158/inhibition-of-sphingosine-1-phosphate-signaling-ameliorates-murine-nonalcoholic-steatohepatitis
#13
Amy S Mauer, Petra Hirsova, Jessica L Maiers, Vijay H Shah, Harmeet Malhi
BACKGROUND: Nonalcoholic steatohepatitis (NASH) is a lipotoxic disorder, wherein proinflammatory lipids, such as ceramide and its derivative sphingosine 1-phosphate (S1P), contribute to macrophage-associated liver inflammation. For example, we have previously demonstrated a role for S1P in steatotic hepatocyte-derived S1P enriched extracellular vesicles in macrophage chemotaxis in vitro. Therefore, we hypothesized that FTY720, an S1P antagonist, would ameliorate NASH by inhibiting proinflammatory monocyte chemotaxis...
December 30, 2016: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28027979/the-impairment-of-glucose-stimulated-insulin-secretion-in-pancreatic-%C3%AE-cells-caused-by-prolonged-glucotoxicity-and-lipotoxicity-is-associated-with-elevated-adaptive-antioxidant-response
#14
Jingqi Fu, Qi Cui, Bei Yang, Yongyong Hou, Huihui Wang, Yuanyuan Xu, Difei Wang, Qiang Zhang, Jingbo Pi
Type 2 diabetes (T2D) is a progressive disease characterized by sustained hyperglycemia and is frequently accompanied by hyperlipidemia. Deterioration of β-cell function in T2D patients may be caused, in part, by long-term exposure to high concentrations of glucose and/or lipids. We developed systems to study how chronic glucotoxicity and lipotoxicity might be linked to the impairment of glucose-stimulated insulin secretion (GSIS) machinery in pancreatic β-cells. INS-1 (832/13) were exposed to glucose and/or palmitate for up to 10 weeks...
December 25, 2016: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28011845/an-inducible-er-golgi-tether-facilitates-ceramide-transport-to-alleviate-lipotoxicity
#15
Li-Ka Liu, Vineet Choudhary, Alexandre Toulmay, William A Prinz
Ceramides are key intermediates in sphingolipid biosynthesis and potent signaling molecules. However, excess ceramide is toxic, causing growth arrest and apoptosis. In this study, we identify a novel mechanism by which cells prevent the toxic accumulation of ceramides; they facilitate nonvesicular ceramide transfer from the endoplasmic reticulum (ER) to the Golgi complex, where ceramides are converted to complex sphingolipids. We find that the yeast protein Nvj2p promotes the nonvesicular transfer of ceramides from the ER to the Golgi complex...
January 2, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28011152/adenosine-a2a-receptor-stimulation-blocks-development-of-nonalcoholic-steatohepatitis-in-mice-by-multilevel-inhibition-of-signals-that-cause-immunolipotoxicity
#16
Elisa Alchera, Simona Rolla, Chiara Imarisio, Valentina Bardina, Guido Valente, Francesco Novelli, Rita Carini
Lipotoxicity and immunoinflammation are associated with the evolution of steatosis toward nonalcoholic steatohepatitis (NASH). This study reports the ability of adenosine A2a receptor (A2aR) activation to inhibit NASH development by modulating the responses of CD4(+) T-helper (Th) cells to avoid an immuno-mediated potentiation of lipotoxicity. The effect of the A2aR agonist CGS21680 on immunoinflammatory signals, CD4(+)Th cell infiltration and immunolipotoxicity was analyzed in steatotic C57BL/6 mice fed with a methionine-choline-deficient (MCD) diet and in mouse hepatocytes exposed to palmitic acid (PA)...
December 6, 2016: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28008587/neutral-ceramidase-secreted-via-exosome-protects-against-palmitate-induced-apoptosis-in-ins-1-cells
#17
S Tang, F Luo, Y M Feng, X Wei, H Miao, Y B Lu, Y Tang, D F Ding, J F Jin, Q Zhu
Aims: To investigate the effects of neutral ceramidase (NCDase) packaged in exosomes that are secreted from β-cells on free fatty acid (FFA)-induced β-cells apoptosis and its role in regulation of sphingolipid-mediated signaling pathway. Methods: HPLC and Western blotting were performed to determine NCDase activity and expression. Annexin V-fluorescein-isothiocyanate/propidium iodide flow cytometry was used to assess apoptosis. Electrospray ionization tandem mass spectrometry was used for ceramide (Cer), sphingosine-1-phosphate (S1P), and sphingosine (SPH) determination...
December 22, 2016: Experimental and Clinical Endocrinology & Diabetes
https://www.readbyqxmd.com/read/28007783/early-pqq-supplementation-has-persistent-long-term-protective-effects-on-developmental-programming-of-hepatic-lipotoxicity-and-inflammation-in-obese-mice
#18
Karen R Jonscher, Michael S Stewart, Alba Alfonso-Garcia, Brian C DeFelice, Xiaoxin X Wang, Yuhuan Luo, Moshe Levi, Margaret J R Heerwagen, Rachel C Janssen, Becky A de la Houssaye, Ellen Wiitala, Garrett Florey, Raleigh L Jonscher, Eric O Potma, Oliver Fiehn, Jacob E Friedman
Nonalcoholic fatty liver disease (NAFLD) is widespread in adults and children. Early exposure to maternal obesity or Western-style diet (WD) increases steatosis and oxidative stress in fetal liver and is associated with lifetime disease risk in the offspring. Pyrroloquinoline quinone (PQQ) is a natural antioxidant found in soil, enriched in human breast milk, and essential for development in mammals. We investigated whether a supplemental dose of PQQ, provided prenatally in a mouse model of diet-induced obesity during pregnancy, could protect obese offspring from progression of NAFLD...
December 22, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27986466/mitochondrial-adaptation-in-nonalcoholic-fatty-liver-disease-novel-mechanisms-and-treatment-strategies
#19
REVIEW
Nishanth E Sunny, Fernando Bril, Kenneth Cusi
Nonalcoholic fatty liver disease (NAFLD) is prevalent in patients with obesity or type 2 diabetes. Nonalcoholic steatohepatitis (NASH), encompassing steatosis with inflammation, hepatocyte injury, and fibrosis, predisposes to cirrhosis, hepatocellular carcinoma, and even cardiovascular disease. In rodent models and humans with NAFLD/NASH, maladaptation of mitochondrial oxidative flux is a central feature of simple steatosis to NASH transition. Induction of hepatic tricarboxylic acid cycle closely mirrors the severity of oxidative stress and inflammation in NASH...
December 13, 2016: Trends in Endocrinology and Metabolism: TEM
https://www.readbyqxmd.com/read/27981808/fluorescing-fatty-acids-in-rat-fatty-liver-models
#20
Anna C Croce, Andrea Ferrigno, Laura G Di Pasqua, Clarissa Berardo, Barbara Mannucci, Giovanni Bottiroli, Mariapia Vairetti
The autofluorescence (AF) of NAD(P)H and flavins has been at the basis of many in-situ studies of liver energy metabolism and functionality. Conversely, few data have been so far reported on fluorescing lipids. In this work we investigated the AF of liver lipid extracts from two fatty liver models, Wistar rats fed with MCD diet for 12 days (Wi-MCD), and obese (fa/fa) Zucker rats. Among the most abundant fatty acids in the lipid extracts, indicated by mass spectrometry, arachidonic acid (AA) exhibited higher quantum yield than the other fluorescing fatty acids (FLFA), and red shifted AF spectrum...
December 16, 2016: Journal of Biophotonics
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