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https://www.readbyqxmd.com/read/29331340/hsp72-protects-from-liver-injury-via-attenuation-of-hepatocellular-death-oxidative-stress-and-jnk-signaling
#1
Kateryna Levada, Nurdan Guldiken, Xiaoji Zhang, Giovanna Vella, Fa-Rong Mo, Laura P James, Johannes Haybaeck, Sonja M Kessler, Alexandra K Kiemer, Thomas Ott, Daniel Hartmann, Norbert Hüser, Marianne Ziol, Christian Trautwein, Pavel Strnad
BACKGROUND AND AIMS: Heat shock protein (Hsp) 72 is a molecular chaperone that is upregulated in response to stress and possesses broad cytoprotective functions. To determine its hepatic function, we studied its expression in human liver disorders and its biological significance in newly generated transgenic animals. AIM AND METHODS: Double transgenic mice overexpressing Hsp72 (gene HSPA1A) under the control of a tissue-specific tetracycline-inducible system (Hsp72-LAP mice) were produced...
January 10, 2018: Journal of Hepatology
https://www.readbyqxmd.com/read/29331057/manifestations-and-mechanisms-of-myocardial-lipotoxicity-in-obesity
#2
Arthur C Sletten, Linda R Peterson, Jean E Schaffer
Environmental and socioeconomic changes over the past thirty years have contributed to a dramatic rise in the worldwide prevalence of obesity. Heart disease is among the most serious health risks of obesity, with increases in both atherosclerotic coronary heart disease and heart failure among obese individuals. In this review, we focus on primary myocardial alterations in obesity that include hypertrophic remodeling and diastolic dysfunction. Obesity-associated perturbations in myocardial and systemic lipid metabolism are important contributors to cardiovascular complications of obesity...
January 13, 2018: Journal of Internal Medicine
https://www.readbyqxmd.com/read/29331050/exercise-counteracts-lipotoxicity-by-improving-lipid-turnover-and-lipid-droplet-quality
#3
Evelyn Zacharewicz, Matthijs K C Hesselink, Patrick Schrauwen
The incidence of obesity and metabolic disease, such as type 2 diabetes mellitus (T2D), are rising globally. Dietary lipid over-supply leads to lipid accumulation at ectopic sites, such as skeletal muscle. Ectopic lipid storage is highly correlated with insulin resistance and T2D, likely due to a loss of metabolic flexibility - the capacity to switch between fat and glucose oxidation upon insulin stimulation - and cellular dysfunction because of lipotoxicity. However, muscle lipid levels are also elevated in endurance trained athletes, presenting a paradoxical phenotype of increased intramuscular lipids along with high insulin sensitivity - the "athletes' paradox"...
January 13, 2018: Journal of Internal Medicine
https://www.readbyqxmd.com/read/29329795/omega-3-fatty-acids-and-adipose-tissue-biology
#4
REVIEW
Ondrej Kuda, Martin Rossmeisl, Jan Kopecky
This review provides evidence for the importance of white and brown adipose tissue (i.e. WAT and BAT) function for the maintenance of healthy metabolic phenotype and its preservation in response to omega-3 polyunsaturated fatty acids (omega-3 PUFA), namely in the context of diseased states linked to aberrant accumulation of body fat, systemic low-grade inflammation, dyslipidemia and insulin resistance. More specifically, the review deals with (i) the concept of immunometabolism, i.e. how adipose-resident immune cells and adipocytes affect each other and define the immune-metabolic interface; and (ii) the characteristic features of "healthy adipocytes" in WAT, which are relatively small fat cells endowed with a high capacity for mitochondrial oxidative phosphorylation, triacylglycerol/fatty acid (TAG/FA) cycling and de novo lipogenesis (DNL)...
January 9, 2018: Molecular Aspects of Medicine
https://www.readbyqxmd.com/read/29323715/alleviation-of-palmitic-acid-induced-endoplasmic-reticulum-stress-by-augmenter-of-liver-regeneration-through-ip3r-controlled-ca2-release
#5
Wei-Chun Xiao, Zhang Jing, Si-Li Chen, Yi-Jun Shi, Fan Xiao, Wei An
The aberrant release of Ca2+ from the endoplasmic reticulum (ER) contributes to the onset of ER stress, which is closely related to the pathogenesis of non-alcoholic fatty liver disease. We previously reported that augmenter of liver regeneration (ALR) alleviates ER stress and protects hepatocytes from lipotoxicity. However, the link between ALR protection and the suppression of ER stress remains unclear. In this study, we investigated whether the protection against liver steatosis afforded by ALR is related to its inhibition of calcium overflow from the ER to the mitochondria...
January 11, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29305172/gastrointestinal-factors-regulating-lipid-droplet-formation-in-the-intestine
#6
REVIEW
N Auclair, L Melbouci, D St-Pierre, E Levy
Cytoplasmic lipid droplets (CLD) are considered as neutral lipid reservoirs, which protect cells from lipotoxicity. It became clear that these fascinating dynamic organelles play a role not only in energy storage and metabolism, but also in cellular lipid and protein handling, inter-organelle communication, and signaling among diverse functions. Their dysregulation is associated with multiple disorders, including obesity, liver steatosis and cardiovascular diseases. The central aim of this review is to highlight the link between intra-enterocyte CLD dynamics and the formation of chylomicrons, the main intestinal dietary lipid vehicle, after overviewing the morphology, molecular composition, biogenesis and functions of CLD...
January 2, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29304720/the-effect-of-cholesterol-overload-on-mouse-kidney-and-kidney-derived-cells
#7
Shoko Honzumi, Miho Takeuchi, Mizuki Kurihara, Masachika Fujiyoshi, Masashi Uchida, Kenta Watanabe, Takaaki Suzuki, Itsuko Ishii
INTRODUCTION: Dyslipidemia is one of the onset and risk factors of chronic kidney disease and renal function drop is seen in lipoprotein abnormal animal models. However, the detailed molecular mechanism of renal lipotoxicity has not been clarified. Therefore, the present study aimed to investigate the influence of cholesterol overload using mouse kidney tissue and kidney-derived cultured cells. METHODS: C57BL/6 mice were fed normal diet (ND) or 1.25% cholesterol-containing high-cholesterol diet (HCD) for 11 weeks, and we used megalin as a proximal tubule marker for immunohistology...
November 2018: Renal Failure
https://www.readbyqxmd.com/read/29284577/distinct-myocardial-targets-for-diabetes%C3%A2-therapy-in-heart-failure-with-preserved-or%C3%A2-reduced-ejection-fraction
#8
REVIEW
Walter J Paulus, Elisa Dal Canto
Noncardiac comorbidities such as diabetes mellitus (DM) have different outcomes in heart failure with preserved ejection fraction (HFpEF) compared with heart failure with reduced ejection fraction (HFrEF). These different outcomes are the result of distinct myocardial effects of DM on HFpEF and HFrEF, which relate to different mechanisms driving myocardial remodeling in each heart failure phenotype. Myocardial remodeling is driven by microvascular endothelial inflammation in HFpEF and by cardiomyocyte cell death in HFrEF...
January 2018: JACC. Heart Failure
https://www.readbyqxmd.com/read/29282281/unbalanced-lipolysis-results-in-lipotoxicity-and-mitochondrial-damage-in-peroxisome-deficient-pex19-mutants
#9
Margret H Bülow, Christian Wingen, Deniz Senyilmaz, Dominic Gosejacob, Mariangela Sociale, Reinhard Bauer, Heike Schulze, Konrad Sandhoff, Aurelio A Teleman, Michael Hoch, Julia Sellin
Inherited Peroxisomal biogenesis disorders (PBDs) are characterized by the absence of functional peroxisomes. They are caused by mutations of peroxisomal biogenesis factors encoded by PEX genes, and result in childhood lethality. Due to the many metabolic functions fulfilled by peroxisomes, PBD pathology is complex and incompletely understood. Besides accumulation of peroxisomal educts (like very long chain fatty acids (VLCFA) or branched chain fatty acids) and lack of products (like bile acids or plasmalogens), many peroxisomal defects lead to detrimental mitochondrial abnormalities for unknown reasons...
December 27, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29258874/is-fatty-acid-composition-of-human-bone-marrow-significant-to-bone-health
#10
Ana María Pino, J Pablo Rodríguez
The bone marrow adipose tissue (BMAT) is a conserved component of the marrow microenvironment, providing storage and release of energy and stabilizing the marrow extent. Also, it is recognized both the amount and quality of BMAT are relevant to preserve the functional relationships between BMAT, bone, and blood cell production. In this article we ponder the information supporting the tenet that the quality of BMAT is relevant to bone health. In the human adult the distribution of BMAT is heterogeneous over the entire skeleton, and both BMAT accumulation and bone loss come about with aging in healthy populations...
December 16, 2017: Bone
https://www.readbyqxmd.com/read/29251796/lipotoxicity-induces-hepatic-protein-inclusions-through-tbk1-mediated-p62-sqstm1-phosphorylation
#11
Chun-Seok Cho, Hwan-Woo Park, Allison Ho, Ian A Semple, Boyoung Kim, Insook Jang, Haeli Park, Shannon Reilly, Alan R Saltiel, Jun Hee Lee
Obesity commonly leads to hepatic steatosis, which often provokes lipotoxic injuries to hepatocytes that cause non-alcoholic steatohepatitis (NASH). NASH in turn is associated with the accumulation of insoluble protein aggregates that are composed of ubiquitinated proteins and ubiquitin adaptor p62/sequestosome 1 (SQSTM1). The formation of p62 inclusions in hepatocytes is the critical marker that distinguishes simple fatty liver from NASH and predicts a poor prognostic outcome for subsequent liver carcinogenesis...
December 18, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29249532/omega-3-pufa-modulate-lipogenesis-er-stress-and-mitochondrial-dysfunction-markers-in-nash-proteomic-and-lipidomic-insight
#12
Lívia Samara Dos Reis Rodrigues Okada, Claudia P Oliveira, José Tadeu Stefano, Monize Aydar Nogueira, Ismael Dale Cotrim Guerreiro da Silva, Fernanda Bertucce Cordeiro, Venâncio Avancini Ferreira Alves, Raquel Susana Torrinhas, Flair José Carrilho, Puneet Puri, Dan L Waitzberg
BACKGROUND & AIMS: Currently there is no FDA-approved therapy for nonalcoholic steatohepatitis (NASH). Increased n-6/n-3 polyunsaturated fatty acids (PUFA) ratio can induce endoplasmic reticulum (ER) stress and mitochondrial dysfunction that characterize NASH. Our recent study with n-3 PUFA showed improvement in individual histologic parameters like steatosis, ballooning and lobular inflammation. We hypothesized that n-3 PUFA therapy mediated improvement in histologic parameters is modulated by lipidomic and proteomic changes...
September 7, 2017: Clinical Nutrition: Official Journal of the European Society of Parenteral and Enteral Nutrition
https://www.readbyqxmd.com/read/29248425/ameliorative-effect-of-panaxynol-on-the-reduction-in-high-molecular-weight-adiponectin-secretion-from-3t3-l1-adipocytes-treated-with-palmitic-acids
#13
Michiyo Takagi, Kazunori Kimura, Ken-Ichi Nakashima, Makoto Inoue
Reduced plasma levels of the high-molecular weight (HMW) form of adiponectin, rather than total adiponectin levels, have been shown to be closely associated with various metabolic diseases including insulin resistance, type 2 diabetes, and cardiovascular disease. Therefore, we sought to explore active, naturally occurring compounds that promote the recovery of HMW adiponectin secretion suppressed by palmitic acid in our model. A total of 90 crude drug extracts were screened for the ability to augment HMW adiponectin secretion from 3T3-L1 adipocytes treated with palmitic acid...
December 14, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29242171/down-regulation-of-stearoyl-coa-desaturase-1-increases-susceptibility-to-palmitic-acid-induced-lipotoxicity-in-human-trophoblast-cells
#14
Changwon Yang, Whasun Lim, Fuller W Bazer, Gwonhwa Song
In early pregnancy, adequate dietary factors are important for the growth of human trophoblast cells, followed by placental development. Although stearoyl-CoA desaturase 1 (SCD1) is expected to relieve palmitic acid (PA)-induced lipotoxicity by regulating diacylglycerol and ceramide, its function is unclear in human trophoblast cells. The aim was to investigate inhibitory effects of SCD1 activity on PA-induced trophoblast cell death. PA induces cell death and inhibits the invasion of human trophoblast cells (HTR8/SVneo)...
November 16, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/29236751/lysophosphatidic-acid-receptor-mrna-levels-in-heart-and-white-adipose-tissue-are-associated-with-obesity-in-mice-and-humans
#15
Amy Brown, Intekhab Hossain, Lester J Perez, Carine Nzirorera, Kathleen Tozer, Kenneth D'Souza, Purvi C Trivedi, Christie Aguiar, Alexandra M Yip, Jennifer Shea, Keith R Brunt, Jean-Francois Legare, Ansar Hassan, Thomas Pulinilkunnil, Petra C Kienesberger
BACKGROUND: Lysophosphatidic acid (LPA) receptor signaling has been implicated in cardiovascular and obesity-related metabolic disease. However, the distribution and regulation of LPA receptors in the myocardium and adipose tissue remain unclear. OBJECTIVES: This study aimed to characterize the mRNA expression of LPA receptors (LPA1-6) in the murine and human myocardium and adipose tissue, and its regulation in response to obesity. METHODS: LPA receptor mRNA levels were determined by qPCR in i) heart ventricles, isolated cardiomyocytes, and perigonadal adipose tissue from chow or high fat-high sucrose (HFHS)-fed male C57BL/6 mice, ii) 3T3-L1 adipocytes and HL-1 cardiomyocytes under conditions mimicking gluco/lipotoxicity, and iii) human atrial and subcutaneous adipose tissue from non-obese, pre-obese, and obese cardiac surgery patients...
2017: PloS One
https://www.readbyqxmd.com/read/29233519/inhibition-of-central-de-novo-ceramide-synthesis-restores-insulin-signaling-in-hypothalamus-and-enhances-%C3%AE-cell-function-of-obese-zucker-rats
#16
Mélanie Campana, Lara Bellini, Claude Rouch, Latif Rachdi, Nicolas Coant, Noémie Butin, Cécile L Bandet, Erwann Philippe, Kelly Meneyrol, Nadim Kassis, Julien Dairou, Eric Hajduch, Benoit Colsch, Christophe Magnan, Hervé Le Stunff
OBJECTIVES: Hypothalamic lipotoxicity has been shown to induce central insulin resistance and dysregulation of glucose homeostasis; nevertheless, elucidation of the regulatory mechanisms remains incomplete. Here, we aimed to determine the role of de novo ceramide synthesis in hypothalamus on the onset of central insulin resistance and the dysregulation of glucose homeostasis induced by obesity. METHODS: Hypothalamic GT1-7 neuronal cells were treated with palmitate...
November 7, 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/29230001/diacylglycerol-triggers-rim101-pathway-dependent-necrosis-in-yeast-a-model-for-lipotoxicity
#17
Patrick Rockenfeller, Martin Smolnig, Jutta Diessl, Mina Bashir, Vera Schmiedhofer, Oskar Knittelfelder, Julia Ring, Joakim Franz, Ines Foessl, Muhammad J Khan, René Rost, Wolfgang F Graier, Guido Kroemer, Andreas Zimmermann, Didac Carmona-Gutierrez, Tobias Eisenberg, Sabrina Büttner, Stephan J Sigrist, Ronald P Kühnlein, Sepp D Kohlwein, Campbell W Gourlay, Frank Madeo
The loss of lipid homeostasis can lead to lipid overload and is associated with a variety of disease states. However, little is known as to how the disruption of lipid regulation or lipid overload affects cell survival. In this study we investigated how excess diacylglycerol (DG), a cardinal metabolite suspected to mediate lipotoxicity, compromises the survival of yeast cells. We reveal that increased DG achieved by either genetic manipulation or pharmacological administration of 1,2-dioctanoyl-sn-glycerol (DOG) triggers necrotic cell death...
December 11, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29229414/lipid-droplets-induced-by-secreted-phospholipase-a2and-unsaturated-fatty-acids-protect-breast-cancer-cells-from-nutrient-and-lipotoxic-stress
#18
Eva Jarc, Ana Kump, Petra Malavašič, Thomas O Eichmann, Robert Zimmermann, Toni Petan
Cancer cells driven by the Ras oncogene scavenge unsaturated fatty acids (FAs) from their environment to counter nutrient stress. The human group X secreted phospholipase A2(hGX sPLA2) releases FAs from membrane phospholipids, stimulates lipid droplet (LD) biogenesis in Ras-driven triple-negative breast cancer (TNBC) cells and enables their survival during starvation. Here we examined the role of LDs, induced by hGX sPLA2and unsaturated FAs, in protection of TNBC cells against nutrient stress. We found that hGX sPLA2releases a mixture of unsaturated FAs, including ω-3 and ω-6 polyunsaturated FAs (PUFAs), from TNBC cells...
December 8, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29225119/d-chiro-inositol-enriched-fagopyrum-tataricum-l-gaench-extract-alleviates-mitochondrial-malfunction-and-inhibits-er-stress-jnk-associated-inflammation-in-the-endothelium
#19
Bobo Zhang, Caifeng Gao, Yunlong Li, Min Wang
ETHNOPHARMACOLOGICAL RELEVANCE: Tartary buckwheat is a food medicine dual-use crop with healing effects on cardiovascular diseases and type2 diabetes. It has been proposed that endothelial dysfunction is the initial lesion in these diseases and it's associated with mitochondrial dysfunction, endoplasmic reticulum (ER) stress and inflammation. D-chiro-inositol (DCI) is a bioactive compound of Tartary buckwheat and is always deficit in type2 diabetes. However, it remains unknown whether DCI-enriched Tartary buckwheat extract can ameliorate mitochondrial dysfunction, ER stress and inflammation in the endothelium...
December 7, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/29224104/the-role-of-estrogens-in-pancreatic-islet-physiopathology
#20
Franck Mauvais-Jarvis, Cedric Le May, Joseph P Tiano, Suhuan Liu, Gamze Kilic-Berkmen, Jun Ho Kim
In rodent models of insulin-deficient diabetes, 17β-estradiol (E2) protects pancreatic insulin-producing β-cells against oxidative stress, amyloid polypeptide toxicity, gluco-lipotoxicity, and apoptosis. Three estrogen receptors (ERs)-ERα, ERβ, and the G protein-coupled ER (GPER)-have been identified in rodent and human β-cells. This chapter describes recent advances in our understanding of the role of ERs in islet β-cell function, nutrient homeostasis, survival from pro-apoptotic stimuli, and proliferation...
2017: Advances in Experimental Medicine and Biology
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