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https://www.readbyqxmd.com/read/28339731/obesity-associated-cardiac-pathogenesis-in-broiler-breeder-hens-development-of-metabolic-cardiomyopathy2-3
#1
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
#2
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
#3
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...
March 24, 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
#4
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
https://www.readbyqxmd.com/read/28322741/evidence-of-k-homeostasis-disruption-in-cellular-dysfunction-triggered-by-7-ketocholesterol-24s-hydroxycholesterol-and-tetracosanoic-acid-c24-0-in-158n-murine-oligodendrocytes
#5
Maryem Bezine, Meryam Debbabi, Thomas Nury, Rym Ben-Khalifa, Mohammad Samadi, Mustapha Cherkaoui-Malki, Anne Vejux, Jérôme de Sèze, Thibault Moreau, Mohamed El-Ayeb, Gérard Lizard
Imbalance in the homeostasis of K(+) ions has been reported to contribute to the pathogenesis of neurodegenerative diseases. 7-ketocholesterol (7KC), 24S-hydroxycholesterol (24S-OHC), and tetracosanoic acid (C24:0), often found at increased levels in patients with Alzheimer's disease, Multiple Sclerosis and X-ALD, are able to trigger numerous nerve cell dysfunctions. We therefore studied the impact of 7KC, 24S-OHC, and C24:0 on 158N murine oligodendrocytes, and determined their impact on K(+) homeostasis. The effects of 7KC, 24S-OHC and C24:0 on lipid membrane organization and membrane potential were examined with merocyanine 540 (MC540) and bis-(1,3-diethylthiobarbituric acid) trimethine oxonol (DiSBAC2(3)), respectively...
March 17, 2017: Chemistry and Physics of Lipids
https://www.readbyqxmd.com/read/28303724/non-alcoholic-fatty-liver-disease-nafld-pathogenesis-classification-and-effect-on-drug-metabolizing-enzymes-and-transporters
#6
Enoch Cobbina, Fatemeh Akhlaghi
Non-alcoholic fatty liver disease (NAFLD) is a spectrum of liver disorders. It is defined by the presence of steatosis in more than 5% of hepatocytes with little or no alcohol consumption. Insulin resistance, the metabolic syndrome or type 2 diabetes and genetic variants of PNPLA3 or TM6SF2 seem to play a role in the pathogenesis of NAFLD. The pathological progression of NAFLD follows tentatively a "three-hit" process namely steatosis, lipotoxicity and inflammation. The presence of steatosis, oxidative stress and inflammatory mediators like TNF-α and IL-6 has been implicated in the alterations of nuclear factors such as CAR, PXR, PPAR-α in NAFLD...
March 17, 2017: Drug Metabolism Reviews
https://www.readbyqxmd.com/read/28298270/nutritional-approaches-to-achieve-weight-loss-in-nonalcoholic-fatty-liver-disease
#7
REVIEW
Christine C Hsu, Erik Ness, Kris V Kowdley
Nonalcoholic fatty liver disease (NAFLD) can range in spectrum from simple hepatic steatosis to nonalcoholic steatohepatitis (NASH), which is characterized by lipotoxicity, hepatocellular ballooning, and inflammation and can progress to cirrhosis. Weight loss is the cornerstone treatment for NAFLD and NASH. Various randomized controlled trials have shown that weight loss of ≥5-10% leads to significant improvements in hepatic steatosis. Diets high in sodium and fructose have been implicated in the pathogenesis of NAFLD...
March 2017: Advances in Nutrition
https://www.readbyqxmd.com/read/28294183/the-endoplasmic-reticulum-stress-autophagy-pathway-is-involved-in-cholesterol-induced-pancreatic-%C3%AE-cell-injury
#8
Fei-Juan Kong, Jia-Hua Wu, Shui-Ya Sun, Jia-Qiang Zhou
Lipotoxicity has been implicated in pancreatic β-cell dysfunction in type 2 diabetes, but the exact mechanisms remain unknown. The current study explored the role of the endoplasmic reticulum (ER) stress pathway in cholesterol-induced lipotoxicity. Two different insulinoma cell lines were treated with cholesterol with or without inhibitors. ER stress-associated proteins glucose-regulated protein (GRP) 78, activating transcription factor (ATF) 4 and C/EBP homologous protein (CHOP), as was phosphorylation of eukaryotic initiation factor (EIF) 2α, were all up-regulated by cholesterol...
March 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28291540/roux-en-y-gastric-bypass-improves-glucose-homeostasis-reduces-oxidative-stress-and-inflammation-in-livers-of-obese-rats-and-in-kupffer-cells-via-an-ampk-dependent-pathway
#9
Yanhua Peng, James Zongyu Li, Min You, Michel M Murr
BACKGROUND: Oxidative stress and inflammation are implicated in the pathogenesis of steatohepatitis. We hypothesize that Roux-en-Y gastric bypass reduces oxidative stress and inflammation in the liver of obese rats via activation of AMPK-α. METHODS: Obese Sprague-Dawley male rats underwent either sham operation or Roux-en-Y gastric bypass. Hepatic TNF-α, NF-κB, IRS-2, PI3 kinase, PKC-ζ, NOX2, and AMPK-α were measured. Mechanistic studies were done in a rat Kupffer cell line (RKC1) that was treated with free fatty acids to mimic lipotoxicity and then transfected with AMPK-α siRNA...
March 10, 2017: Surgery
https://www.readbyqxmd.com/read/28290604/glucagon-like-peptide-1-receptor-agonist-ameliorates-the-insulin-resistance-function-of-islet-%C3%AE-cells-via-the-activation-of-pdx-1-jak-signaling-transduction-in-c57-bl6-mice-with-high-fat-diet-induced-diabetes
#10
Tao Hao, Hongtao Zhang, Sheyu Li, Haoming Tian
Long-term exposure to a high-fat diet (HFD) causes glucotoxicity and lipotoxicity in islet β cells and leads to the development of metabolic dysfunctions. Reductions in pancreatic and duodenal homeobox-1 (PDX-1) expression have been shown to induce type 2 diabetes mellitus by causing impairments to islet β cells. Glucagon-like peptide 1 (GLP-1) treatment reduces endogenous insulin resistance in HFD-induced type 2 diabetes mellitus. In the present study, the underlying mechanism by which GLP-1 exerts its function in type 2 diabetes mellitus was investigated...
March 7, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28277987/endoc-%C3%AE-h1-cells-display-increased-sensitivity-to-sodium-palmitate-when-cultured-in-dmem-f12-medium
#11
Camilla Krizhanovskii, Hjalti Kristinsson, Andris Elksnis, Xuan Wang, Hamid Gavali, Peter Bergsten, Raphael Scharfmann, Nils Welsh
Aims - Human pancreatic islets are known to die in response to the free fatty acid of sodium palmitate when cultured in vitro. This is in contrast to EndoC-βH1 cells, which in our hands are not sensitive to the cell death-inducing effects sodium palmitate, making these cells seemingly unsuitable for lipotoxicity studies. However, the EndoC-βH1 cells are routinely cultured in a nutrient mixture based on Dulbecco's Modified Eagle Medium (DMEM), which may not be the optimal choice for studies dealing with lipotoxicity...
February 28, 2017: Islets
https://www.readbyqxmd.com/read/28276774/pharmacological-management-of-nonalcoholic-fatty-liver-disease-in-type-2-diabetes
#12
Simona Cernea, Avivit Cahn, Itamar Raz
The prevalence of nonalcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes (T2D) is high and it is associated with poor prognosis. Hepatic steatosis results as a consequence of excessive hepatic lipid accumulation which correlates with insulin resistance and lipotoxicity, with subsequent oxidative stress, inflammation, apoptosis and fibrosis. Areas covered: This article presents the main pathophysiologic mechanisms and currently available drugs evaluated for their therapeutic effects on NAFLD/nonalcoholic steatohepatitis (NASH) and drugs under development that target relevant pathogenetic pathways...
March 6, 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28265821/suppression-of-rho-kinase-1-is-responsible-for-insulin-regulation-of-the-ampk-srebp-1c-pathway-in-skeletal-muscle-cells-exposed-to-palmitate
#13
Sunyinyan Tang, Wenjun Wu, Wenjuan Tang, Zhijuan Ge, Hongdong Wang, Ting Hong, Dalong Zhu, Yan Bi
AIMS: Clinical and experimental data suggest that early insulin therapy could reduce lipotoxicity in subjects and animal models with type 2 diabetes mellitus. However, the underlying mechanisms need to be clarified. Sterol regulatory element-binding protein 1c (SREBP-1c), which is negatively regulated by AMP-activated protein kinase (AMPK), plays a critical role in lipotoxicity and insulin resistance in skeletal muscle cells. Here, we investigated the effect and molecular mechanism of insulin intervention on the AMPK/SREBP-1c pathway in skeletal muscle cells with chronic exposure to palmitic acid (PA)...
March 7, 2017: Acta Diabetologica
https://www.readbyqxmd.com/read/28263859/improvement-of-metabolic-disorders-by-an-ep-2-receptor-agonist-via-restoration-of-the-subcutaneous-adipose-tissue-in-pulmonary-emphysema
#14
Takao Tsuji, Kazuhiro Yamaguchi, Ryota Kikuchi, Hiroyuki Nakamura, Ryoichi Misaka, Atsushi Nagai, Kazutetsu Aoshiba
Chronic obstructive pulmonary disease (COPD) is often associated with co-morbidities. Metabolic disorders like hyperlipidemia and diabetes occur also in underweight COPD patients, although the mechanism is uncertain. Subcutaneous adipose tissue (SAT) plays an important role in energy homeostasis, since restricted capacity to increase fat cell number with increase in fat cell size occurring instead, is associated with lipotoxicity and metabolic disorders. The aim of this study is to show the protective role of SAT for the metabolic disorders in pulmonary emphysema of a murine model...
March 2, 2017: Prostaglandins & Other Lipid Mediators
https://www.readbyqxmd.com/read/28262979/mixed-lineage-kinase-3-mediates-the-induction-of-cxcl10-by-a-stat1-dependent-mechanism-during-hepatocyte-lipotoxicity
#15
Kyoko Tomita, Ayano Niibe, Brittany L Freeman, Steven F Bronk, Petra Hirsova, Samar H Ibrahim
BACKGROUND AND AIMS: Saturated free fatty acids (SFA) and their toxic metabolites contribute to hepatocyte lipotoxicity in nonalcoholic steatohepatitis (NASH). We previously reported that hepatocytes, under lipotoxic stress, express the potent macrophage chemotactic ligand C-X-C motif chemokine 10 (CXCL10) and release CXCL10-enriched extracellular vesicles by a mixed lineage kinase (MLK) 3-dependent mechanism. In the current study, we sought to examine the signaling pathway responsible for CXCL10 induction during hepatocyte lipotoxicity...
March 6, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28261588/comparison-of-visceral-fat-accumulation-and-metabolome-markers-among-cats-of-varying-bcs-and-novel-classification-of-feline-obesity-and-metabolic-syndrome
#16
Yuki Okada, Motoo Kobayashi, Masaki Sawamura, Toshiro Arai
As in humans, obesity and its associated diseases represent the most significant threat to the health of veterinary populations. Previous human studies have provided insights into the risk factors of obesity, complex pathogenesis of obesity-associated diseases, and their life-threatening consequences. In humans, the "metabolic syndrome" represents a cluster of metabolic risk factors associated with the development of cardiovascular disease. Risk factors for metabolic syndrome, such as diabetes, obesity, high blood pressure, and its complications increase health-care utilization and medical expenses...
2017: Frontiers in Veterinary Science
https://www.readbyqxmd.com/read/28250026/foxo3-increases-mir-34a-to-cause-palmitate-induced-cholangiocyte-lipoapoptosis
#17
Sathish Kumar Natarajan, Bailey A Stringham, Ashley M Mohr, Cody J Wehrkamp, Sizhao Lu, Mary Anne Phillippi, Dee Harrison-Findik, Justin L Mott
Non-alcoholic steatohepatitis (NASH) patients have elevated plasma saturated free fatty acid levels. These toxic fatty acids can induce liver cell death and our recent results demonstrated that the biliary epithelium may be susceptible to lipotoxicity. Here, we explored the molecular mechanisms of cholangiocyte lipoapoptosis in cell culture and in an animal model of NASH. Treatment of cholangiocytes with palmitate showed increased caspase-3/7 activity, and increased levels of cleaved PARP and cleaved caspase 3 demonstrating cholangiocyte lipoapoptosis...
March 1, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28249257/therapeutic-mechanisms-of-bile-acids-and-nor-ursodeoxycholic-acid-in-non-alcoholic-fatty-liver-disease
#18
Daniel Steinacher, Thierry Claudel, Michael Trauner
Non-alcoholic fatty liver disease is one of the most rapidly rising clinical problems in the 21st century. So far no effective drug treatment has been established to cure this disease. Bile acids (BAs) have a variety of signaling properties, which can be used therapeutically for modulating hepatic metabolism and inflammation. A side-chain shorted derivative of ursodeoxycholic acid (UDCA) is 24 nor-ursodeoxycholic acid (NorUDCA) and it represents a new class of drugs for treatment of liver diseases. NorUDCA has unique biochemical and therapeutic properties, since it is relatively resistant to conjugation with glycine or taurine compared to UDCA...
2017: Digestive Diseases
https://www.readbyqxmd.com/read/28249154/%C3%AE-hydroxybutyrate-deactivates-neutrophil-nlrp3-inflammasome-to-relieve-gout-flares
#19
Emily L Goldberg, Jennifer L Asher, Ryan D Molony, Albert C Shaw, Caroline J Zeiss, Chao Wang, Ludmilla A Morozova-Roche, Raimund I Herzog, Akiko Iwasaki, Vishwa Deep Dixit
Aging and lipotoxicity are two major risk factors for gout that are linked by the activation of the NLRP3 inflammasome. Neutrophil-mediated production of interleukin-1β (IL-1β) drives gouty flares that cause joint destruction, intense pain, and fever. However, metabolites that impact neutrophil inflammasome remain unknown. Here, we identified that ketogenic diet (KD) increases β-hydroxybutyrate (BHB) and alleviates urate crystal-induced gout without impairing immune defense against bacterial infection. BHB inhibited NLRP3 inflammasome in S100A9 fibril-primed and urate crystal-activated macrophages, which serve to recruit inflammatory neutrophils in joints...
February 28, 2017: Cell Reports
https://www.readbyqxmd.com/read/28249038/microvesicles-released-from-fat-laden-cells-promote-activation-of-hepatocellular-nlrp3-inflammasome-a-pro-inflammatory-link-between-lipotoxicity-and-non-alcoholic-steatohepatitis
#20
Stefania Cannito, Elisabetta Morello, Claudia Bocca, Beatrice Foglia, Elisa Benetti, Erica Novo, Fausto Chiazza, Mara Rogazzo, Roberto Fantozzi, Davide Povero, Salvatore Sutti, Elisabetta Bugianesi, Ariel E Feldstein, Emanuele Albano, Massimo Collino, Maurizio Parola
Non-Alcoholic Fatty Liver Disease (NAFLD) is a major form of chronic liver disease in the general population in relation to its high prevalence among overweight/obese individuals and patients with diabetes type II or metabolic syndrome. NAFLD can progress to steatohepatitis (NASH), fibrosis and cirrhosis and end-stage of liver disease but mechanisms involved are still incompletely characterized. Within the mechanisms proposed to mediate the progression of NAFLD, lipotoxicity is believed to play a major role...
2017: PloS One
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