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Steatosis hepatic

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https://www.readbyqxmd.com/read/29792946/investigation-of-nonalcoholic-fatty-liver-disease-induced-drug-metabolism-by-comparative-global-toxicoproteomics
#1
Ann-Yae Na, Jung Jae Jo, Ok Kwang Kwon, Riya Shrestha, Piljoung Cho, Kyu Min Kim, Sung Hwan Ki, Tae Hee Lee, Tae Won Jeon, Tae Cheon Jeong, Sangkyu Lee
Non-alcoholic fatty liver disease (NAFLD) includes conditions such as steatosis, non-alcoholic steatohepatitis, and ultimately hepatocellular carcinoma. Although the pathology of NAFLD is well-established, NAFLD-induced drug metabolism mediated by cytochrome P450 (CYP) in the liver has remained largely unexplored. Therefore, we investigated NAFLD-induced drug metabolism mediated by CYP by quantitative toxicoproteomics analysis. After administration of a methionine-choline deficient (MCD) diet to induce development of NAFLD, tandem mass tags-based liquid chromatography-tandem mass spectrometry analysis was conducted to investigate the dynamics of hepatic proteins...
May 21, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29792584/neonatal-intake-of-oleanolic-acid-attenuates-the-subsequent-development-of-high-fructose-diet-induced-non-alcoholic-fatty-liver-disease-in-rats
#2
T T Nyakudya, E Mukwevho, P Nkomozepi, K H Erlwanger
Dietary manipulations during the early postnatal period are associated with the development of metabolic disorders including non-alcoholic fatty liver disease (NAFLD) or long-term protection against metabolic dysfunction. We investigated the potential hepatoprotective effects of neonatal administration of oleanolic acid (OA), a phytochemical, on the subsequent development in adulthood, of dietary fructose-induced NAFLD. Male and female suckling rats (n=112) were gavaged with; distilled water (DW), OA (60 mg/kg), high fructose solution (HF; 20% w/v) and OA+HF (OAHF) for 7 days...
May 24, 2018: Journal of Developmental Origins of Health and Disease
https://www.readbyqxmd.com/read/29792338/molecular-mechanism-for-the-influence-of-gender-dimorphism-on-alcoholic-liver-injury-in-mice
#3
S-Q Li, P Wang, D-M Wang, H-J Lu, R-F Li, L-X Duan, S Zhu, S-L Wang, Y-Y Zhang, Y-L Wang
It is known that women develop alcoholic liver injury more rapidly and have a lower alcohol toxic threshold than men. However, the detailed molecular mechanisms remain unclear. The precise mechanism responsible for the sex difference needs to be determined. Female and male mice were given ethanol by intragastric infusion every day for 4 weeks. The pathological changes were detected by hematoxylin-eosin, Sirius red, oil red O, periodic acid-Schiff, and Hochest33258 staining in the liver of female and male mice...
January 1, 2018: Human & Experimental Toxicology
https://www.readbyqxmd.com/read/29790582/acetyl-coa-carboxylase-inhibition-reverses-nafld-and-hepatic-insulin-resistance-but-promotes-hypertriglyceridemia-in-rodents
#4
Leigh Goedeke, Jamie Bates, Daniel F Vatner, Rachel J Perry, Ting Wang, Ricardo Ramirez, Li Li, Matthew W Ellis, Dongyan Zhang, Kari E Wong, Carine Beysen, Gary W Cline, Adrian S Ray, Gerald I Shulman
Pharmacologic inhibition of acetyl-CoA carboxylase (ACC) enzymes, ACC1 and ACC2, offers an attractive therapeutic strategy for non-alcoholic fatty liver disease (NAFLD) via simultaneous inhibition of fatty acid synthesis and stimulation of fatty acid oxidation. However, the effects of ACC inhibition on hepatic mitochondrial oxidation, anaplerosis, and ketogenesis in vivo are unknown. Here, we evaluated the impact of a novel liver-directed allosteric inhibitor of ACC1 and ACC2 (Compound 1) on these parameters, as well as glucose and lipid metabolism, in control and diet-induced rodent models of NAFLD...
May 23, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29789270/surplus-fat-rapidly-increases-fat-oxidation-and-insulin-resistance-in-lipodystrophic-mice
#5
Amandine Girousse, Samuel Virtue, Dan Hart, Antonio Vidal-Puig, Peter R Murgatroyd, Etienne Mouisel, Coralie Sengenès, David B Savage
OBJECTIVE: Surplus dietary fat cannot be converted into other macronutrient forms or excreted, so has to be stored or oxidized. Healthy mammals store excess energy in the form of triacylgycerol (TAG) in lipid droplets within adipocytes rather than oxidizing it, and thus ultimately gain weight. The 'overflow hypothesis' posits that the capacity to increase the size and number of adipocytes is finite and that when this limit is exceeded, fat accumulates in ectopic sites and leads to metabolic disease...
May 16, 2018: Molecular Metabolism
https://www.readbyqxmd.com/read/29787476/maternal-physical-activity-and-sex-impact-markers-of-hepatic-mitochondrial-health
#6
Rory P Cunningham, Mary P Moore, Grace M Meers, Gregory N Ruegsegger, Frank W Booth, R Scott Rector
INTRODUCTION: Maternal exercise and physical activity during the gestational period can be protective against maternal high fat diet-induced hepatic steatosis in older offspring. However, it is unknown whether these protective effects are seen in younger offspring. Here we investigated whether maternal physical activity would attenuate maternal western diet (WD)-induced steatosis in young adult rats. METHODS: Female Wistar rats (7-8 weeks of age) were randomized into WD (42% fat, 27% sucrose) or normal chow diet (ND), and further randomized into physical activity (RUN) or sedentary (SED) conditions for a total of four groups...
May 22, 2018: Medicine and Science in Sports and Exercise
https://www.readbyqxmd.com/read/29786674/choline-supplementation-prevents-a-hallmark-disturbance-of-kwashiorkor-in-weanling-mice-fed-a-maize-vegetable-diet-hepatic-steatosis-of-undernutrition
#7
Thaddaeus May, Kevin C Klatt, Jacob Smith, Eumenia Castro, Mark Manary, Marie A Caudill, Farook Jahoor, Marta L Fiorotto
Hepatic steatosis is a hallmark feature of kwashiorkor malnutrition. However, the pathogenesis of hepatic steatosis in kwashiorkor is uncertain. Our objective was to develop a mouse model of childhood undernutrition in order to test the hypothesis that feeding a maize vegetable diet (MVD), like that consumed by children at risk for kwashiorkor, will cause hepatic steatosis which is prevented by supplementation with choline. A MVD was developed with locally sourced organic ingredients, and fed to weanling mice ( n = 9) for 6 or 13 days...
May 22, 2018: Nutrients
https://www.readbyqxmd.com/read/29785143/pilot-study-of-the-antifibrotic-effects-of-the-multikinase-inhibitor-pacritinib-in-a-mouse-model-of-liver-fibrosis
#8
Suliman Al-Fayoumi, Taishi Hashiguchi, Yuka Shirakata, John Mascarenhas, Jack W Singer
Background: Fibrotic diseases result from an exuberant response to chronic inflammation. Myelofibrosis is the end result of inflammation in bone, caused by an inflammatory process triggered by production of abnormal myeloid cells driven by mutations affecting the JAK-STAT pathway. Inflammatory cytokine overproduction leads to increased mesenchymal cell proliferation, culminating in fibrosis. Although JAK2 inhibitors, such as the JAK1/2 inhibitor ruxolitinib and the JAK2/FLT3/CSF1R/IRAK1 inhibitor pacritinib suppress abnormal clone expansion in myelofibrosis, ruxolitinib does not appear to prevent or reverse bone-marrow fibrosis in most patients...
2018: Journal of Experimental Pharmacology
https://www.readbyqxmd.com/read/29784585/inhibition-of-glycogen-synthase-ii-with-rnai-prevents-liver-injury-in-mouse-models-of-glycogen-storage-diseases
#9
Natalie Pursell, Jessica Gierut, Wei Zhou, Michael Dills, Rohan Diwanji, Monika Gjorgjieva, Utsav Saxena, Jr-Shiuan Yang, Anee Shah, Nandini Venkat, Rachel Storr, Boyoung Kim, Weimin Wang, Marc Abrams, Margaux Raffin, Gilles Mithieux, Fabienne Rajas, Henryk Dudek, Bob D Brown, Chengjung Lai
Glycogen storage diseases (GSDs) of the liver are devastating disorders presenting with fasting hypoglycemia as well as hepatic glycogen and lipid accumulation, which could lead to long-term liver damage. Diet control is frequently utilized to manage the potentially dangerous hypoglycemia, but there is currently no effective pharmacological treatment for preventing hepatomegaly and concurrent liver metabolic abnormalities, which could lead to fibrosis, cirrhosis, and hepatocellular adenoma or carcinoma. In this study, we demonstrate that inhibition of glycogen synthesis using an RNAi approach to silence hepatic Gys2 expression effectively prevents glycogen synthesis, glycogen accumulation, hepatomegaly, fibrosis, and nodule development in a mouse model of GSD III...
April 27, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/29784251/corrigendum-to-sennoside-a-protects-mitochondrial-structure-and-function-to-improve-high-fat-diet-induced-hepatic-steatosis-by-targeting-vdac1-biochem-biophys-res-commun-500-2018-484-489
#10
Jiamei Le, Weiping Jia, Yongning Sun
No abstract text is available yet for this article.
May 18, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29782848/impaired-tfeb-mediated-lysosome-biogenesis-and-autophagy-promote-chronic-ethanol-induced-liver-injury-and-steatosis-in-mice
#11
Xiaojuan Chao, Shaogui Wang, Katrina Zhao, Yuan Li, Jessica A Williams, Tiangang Li, Hemantkumar Chavan, Partha Krishnamurthy, Xi C He, Linheng Li, Andrea Ballabio, Hong-Min Ni, Wen-Xing Ding
BACKGROUND & AIMS: Defects in lysosome function and autophagy contribute to pathogenesis of alcoholic liver disease. We investigated the mechanisms by which alcohol consumption affects these processes, evaluating the functions transcription factor EB (TFEB), which regulates lysosomal biogenesis. METHODS: We performed studies with GFP-LC3 mice, mice with liver-specific deletion of transcription factor EB (TFEB), mice with disruption of the transcription factor E3 gene (TFE3-knockout mice), mice with disruption of the Tefb and Tfe3 genes (TFEB, TFE3 double-knockout mice), and Tfebflox/flox albumin cre-negative mice (controls)...
May 18, 2018: Gastroenterology
https://www.readbyqxmd.com/read/29779826/the-bckdh-kinase-and-phosphatase-integrate-bcaa-and-lipid-metabolism-via-regulation-of-atp-citrate-lyase
#12
Phillip J White, Robert W McGarrah, Paul A Grimsrud, Shih-Chia Tso, Wen-Hsuan Yang, Jonathan M Haldeman, Thomas Grenier-Larouche, Jie An, Amanda L Lapworth, Inna Astapova, Sarah A Hannou, Tabitha George, Michelle Arlotto, Lyra B Olson, Michelle Lai, Guo-Fang Zhang, Olga Ilkayeva, Mark A Herman, R Max Wynn, David T Chuang, Christopher B Newgard
Branched-chain amino acids (BCAA) are strongly associated with dysregulated glucose and lipid metabolism, but the underlying mechanisms are poorly understood. We report that inhibition of the kinase (BDK) or overexpression of the phosphatase (PPM1K) that regulates branched-chain ketoacid dehydrogenase (BCKDH), the committed step of BCAA catabolism, lowers circulating BCAA, reduces hepatic steatosis, and improves glucose tolerance in the absence of weight loss in Zucker fatty rats. Phosphoproteomics analysis identified ATP-citrate lyase (ACL) as an alternate substrate of BDK and PPM1K...
May 11, 2018: Cell Metabolism
https://www.readbyqxmd.com/read/29779170/histological-improvement-of-non-alcoholic-steatohepatitis-with-a-prebiotic-a-pilot-clinical-trial
#13
Marc R Bomhof, Jill A Parnell, Hena R Ramay, Pam Crotty, Kevin P Rioux, Chris S Probert, Saumya Jayakumar, Maitreyi Raman, Raylene A Reimer
PURPOSE: In obesity and diabetes the liver is highly susceptible to abnormal uptake and storage of fat. In certain individuals hepatic steatosis predisposes to the development of non-alcoholic steatohepatitis (NASH), a disease marked by hepatic inflammation and fibrosis. Although the precise pathophysiology of NASH is unknown, it is believed that the gut microbiota-liver axis influences the development of this disease. With few treatment strategies available for NASH, exploration of gut microbiota-targeted interventions is warranted...
May 19, 2018: European Journal of Nutrition
https://www.readbyqxmd.com/read/29777756/peroxiredoxin-5-regulates-adipogenesis-attenuating-oxidative-stress-in-obese-mouse-models-induced-by-a-high-fat-diet
#14
Mi Hye Kim, Sun-Ji Park, Jung-Hak Kim, Jung Bae Seong, Kyung-Min Kim, Hyun Ae Woo, Dong-Seok Lee
Elevated levels of reactive oxygen species (ROS) are a hallmark of obesity. Peroxiredoxin 5 (Prx5), which is a cysteine-dependent peroxidase enzyme, has an intensive ROS scavenging activity because it is located in the cytosol and mitochondria. Therefore, we focused on the role of Prx5 in regulating mitochondrial ROS and adipogenesis. We demonstrated that Prx5 expression was upregulated during adipogenesis and Prx5 overexpression suppressed adipogenesis by regulating cytosolic and mitochondrial ROS generation...
May 16, 2018: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29777706/n-3-polyunsaturated-fatty-acids-ameliorate-hepatic-steatosis-via-the-ppar-%C3%AE-cpt-1%C3%AE-pathway-in-a-mouse-model-of-parenteral-nutrition
#15
Feng Tian, Jiwei Wang, Haifeng Sun, Jianbo Yang, Peng Wang, Songlin Wan, Xuejin Gao, Li Zhang, Jieshou Li, Xinying Wang
Parenteral nutrition (PN) is one of the basic therapies for patients with intestinal failure; however, hepatic steatosis associated with PN limits the long-term use of PN. N-3 polyunsaturated fatty acids (PUFAs) have been used to improve clinical outcomes of patients receiving PN; however, the mechanisms by which n-3 PUFAs ameliorate hepatic steatosis remain unclear. In the present study, C57BL/6J mice were randomly assigned to three treatment groups, namely, enteral nutrition (EN), n-3 PUFAs, and n-6 PUFAs...
May 16, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29777704/dietary-mung-bean-protein-reduces-high-fat-diet-induced-weight-gain-by-modulating-host-bile-acid-metabolism-in-a-gut-microbiota-dependent-manner
#16
Akiho Nakatani, Xuan Li, Junki Miyamoto, Miki Igarashi, Hitoshi Watanabe, Asuka Sutou, Keita Watanabe, Takayasu Motoyama, Nobuhiko Tachibana, Mitsutaka Kohno, Hiroshi Inoue, Ikuo Kimura
The 8-globulin-rich mung bean protein (MPI) suppresses hepatic lipogenesis in rodent models and reduces fasting plasma glucose and insulin levels in obese adults. However, its effects on mitigating high fat diet (HFD)-induced obesity and the mechanism underlying these effects remain to be elucidated. Herein, we examined the metabolic phenotype, intestinal bile acid (BA) pool, and gut microbiota of conventionally raised (CONV-R) male C57BL/6 mice and germ-free (GF) mice that were randomized to receive either regular HFD or HFD containing mung bean protein isolate (MPI) instead of the dairy protein present in regular HFD...
May 16, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29777191/eradication-of-hepatitis-c-virus-is-associated-with-the-attenuation-of-steatosis-as-evaluated-using-a-controlled-attenuation-parameter
#17
Kohei Shimizu, Yoko Soroida, Masaya Sato, Hiromi Hikita, Tamaki Kobayashi, Momoe Endo, Mamiko Sato, Hiroaki Gotoh, Tomomi Iwai, Ryosuke Tateishi, Kazuhiko Koike, Yutaka Yatomi, Hitoshi Ikeda
Chronic hepatitis C virus (HCV) infection was shown to cause hepatic steatosis or suppression of serum lipid levels. However, little is known about the changes in hepatic steatosis following HCV eradication. We aimed to evaluate this issue using the controlled attenuation parameter (CAP), which was recently shown to provide a standardized non-invasive measure of hepatic steatosis. We enrolled 70 patients with chronic HCV infections and steatosis (CAP of over 248 dB/m) who had achieved a sustained viral response at 12 weeks after discontinuation of antiviral treatment using direct-acting antivirals (DAA)...
May 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29775936/from-hit-to-lead-structure-based-discovery-of-naphthalene-1-sulfonamide-derivatives-as-potent-and-selective-inhibitors-of-fatty-acid-binding-protein-4
#18
Ding-Ding Gao, Hui-Xia Dou, Hai-Xia Su, Ming-Ming Zhang, Ting Wang, Qiu-Feng Liu, Hai-Yan Cai, Hai-Peng Ding, Zhuo Yang, Wei-Liang Zhu, Ye-Chun Xu, He-Yao Wang, Ying-Xia Li
Fatty acid binding protein 4 (FABP4) plays a critical role in metabolism and inflammatory processes and therefore is a potential therapeutic target for immunometabolic diseases such as diabetes and atherosclerosis. Herein, we reported the identification of naphthalene-1-sulfonamide derivatives as novel, potent and selective FABP4 inhibitors by applying a structure-based design strategy. The binding affinities of compounds 16dk, 16do and 16du to FABP4, at the molecular level, are equivalent to or even better than that of BMS309403...
May 9, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29774529/inhibition-of-prmt3-activity-selectively-impairs-lxr-driven-transcription-of-hepatic-lipogenic-genes-in-vivo
#19
Joya E Nahon, Christianne Groeneveldt, Janine J Geerling, Miranda Van Eck, Menno Hoekstra
BACKGROUND AND PURPOSE: Agonists for the liver X receptor (LXR) are considered promising therapeutic moieties in cholesterol-driven diseases by promoting cellular cholesterol efflux pathways. However, current clinical application of these agents is hampered by the concomitant LXR-induced activation of a lipogenic transcriptional network, leading to hepatic steatosis. Recent studies have suggested that protein arginine methyltransferase 3 (PRMT3) may act as a selective co-activator of LXR activity...
May 18, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29773823/comparison-of-conventional-sonographic-signs-and-magnetic-resonance-imaging-proton-density-fat-fraction-for-assessment-of-hepatic-steatosis
#20
Mimi Kim, Bo-Kyeong Kang, Dae Won Jun
This study correlated conventional ultrasonography (US) signs with the magnetic resonance imaging (MRI) proton density fat fraction (PDFF) to evaluate the diagnostic performance of US signs (alone or combined) to predict presence and degree of hepatic steatosis (HS). Overall, 182 subjects met the study inclusion criteria between February 2014 and October 2016. Four US signs were evaluated independently by two radiologists. MRI PDFF was defined as the average of 24 non-overlapping regions of interest (ROIs) within eight liver segments obtained by drawing three ROIs within each segment...
May 17, 2018: Scientific Reports
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