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https://www.readbyqxmd.com/read/29587349/evaluation-of-two-liver-treatment-strategies-in-a-mouse-model-of-niemann-pick-disease-type-c1
#1
Lynn Ebner, Anne Gläser, Anja Bräuer, Martin Witt, Andreas Wree, Arndt Rolfs, Marcus Frank, Brigitte Vollmar, Angela Kuhla
Niemann-Pick-disease type C1 (NPC1) is an autosomal-recessive cholesterol-storage disorder. Besides other symptoms, NPC1 patients develop liver dysfunction and hepatosplenomegaly. The mechanisms of hepatomegaly and alterations of lipid metabolism-related genes in NPC1 disease are still poorly understood. Here, we used an NPC1 mouse model to study an additive hepatoprotective effect of a combination of 2-hydroxypropyl-β-cyclodextrin (HPβCD), miglustat and allopregnanolone (combination therapy) with the previously established monotherapy using HPβCD...
March 24, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29533741/myeloid-specific-acat1-ablation-attenuates-inflammatory-responses-in-macrophages-improves-insulin-sensitivity-and-suppresses-diet-induced-obesity
#2
Li-Hao Huang, Elaina M Melton, Haibo Li, Paul Sohn, DaeYoung Jung, Ching-Yi Tsai, Tian Ma, Hiroyuki Sano, HyeKyung Ha, Randall H Friedline, Jason K Kim, Edward Usherwood, Catherine Cy Chang, Ta-Yuan Chang
Macrophages are phagocytes that play important roles in health and diseases. Acyl-CoA:cholesterol acyltransferase 1 [ACAT1] converts cellular cholesterol to cholesteryl esters, and is expressed in many cell types. Unlike global Acat1 knockout [KO], myeloid-specific Acat1 KO [Acat1-M/-M ] does not cause overt abnormalities in mice. Here we performed analyses in age and sex matched Acat1-M/-M and wild-type mice on chow or Western diet, and discovered that Acat1-M/-M mice exhibit resistance to Western diet-induced obesity...
March 13, 2018: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29486586/single-cell-transcriptomics-of-human-oocytes-environment-driven-metabolic-competition-and-compensatory-mechanisms-during-oocyte-maturation
#3
Hongcui Zhao, Tianjie Li, Yue Zhao, Tao Tan, Changyu Liu, Yali Liu, Liang Chang, Ning Huang, Chang Li, Yong Fan, Yang Yu, Rong Li, Jie Qiao
AIM: The mechanisms coordinating maturation with an environment-driven metabolic shift, a critical step in determining the developmental potential of human in vitro matured (IVM) oocytes, remains to be elucidated. Here, we explored the key genes regulating human oocyte maturation using single-cell RNA sequencing and illuminated the compensatory mechanism from a metabolic perspective by analyzing gene expression. RESULTS: Three key genes that encode CoA-related enzymes were screened from the RNA sequencing data...
February 27, 2018: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/29469041/natural-extracts-abolished-lipid-accumulation-in-cells-harbouring-non-favourable-pnpla3-genotype
#4
Ángela Rojas, Paloma Gallego, Antonio Gil-Gómez, Rocío Muñoz-Hernández, Lourdes Rojas, Rosario Maldonado, Rocío Gallego, Marta García-Valdecasas, José A Del Campo, Juan D Bautista, Manuel Romero-Gómez
Background & aims. G-allele of PNPLA3 (rs738409) favours triglycerides accumulation and steatosis. In this study, we examined the effect of quercetin and natural extracts from mushroom and artichoke on reducing lipid accumulation in hepatic cells. MATERIAL AND METHODS: Huh7.5 cells were exposed to oleic acid (OA) and treated with quercetin and extracts to observe the lipid accumulation, the intracellular-TG concentration and the LD size. Sterol regulatory element binding proteins-1 (SREBP-1), peroxisome proliferator-activated receptor (PPARα-γ) and cholesterol acyltransferase (ACAT) gene expression levels were analysed...
March 1, 2018: Annals of Hepatology
https://www.readbyqxmd.com/read/29382421/-the-oxldl-%C3%AE-2gpi-anti-%C3%AE-2gpi-antibody-complex-promotes-a7r5-chemotaxis-migration-and-lipid-accumulation
#5
Hang Ouyang, Hong Zhou, Chao He, Guiting Zhang, Yudan Chen, Ting Wang, Xiaoyan Wang, Peng Zhang
Objective To explore the effect of the oxidized low-density lipoprotein/β2 -glycoprotein I/β2 glycoprotein I antibody (oxLDL/β2GPI/β2GPI-Ab) complex on the migration, chemotaxis and lipid accumulation of rat thoracic aortic smooth muscle A7r5 cell line, and unveil the role of Toll-like receptor 4 (TLR4) pathway during the process. Methods A7r5 cells were cultured in vitro with or without the pretreatment of TAK-242, a TLR4 inhibitor. Then the cells were stimulated by oxLDL, oxLDL/β2GPI complex, β2GPI, β2GPI-Ab, β2GPI/β2GPI-Ab complex or oxLDL/β2GPI/β2GPI-Ab complex...
December 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/29247843/dietary-betaine-supplementation-in-hens-modulates-hypothalamic-expression-of-cholesterol-metabolic-genes-in-f1-cockerels-through-modification-of-dna-methylation
#6
Abdulrahman A Idriss, Yun Hu, Zhen Hou, Yan Hu, Qinwei Sun, Nagmeldin A Omer, Halima Abobaker, Yingdong Ni, Ruqian Zhao
Betaine is widely used in animal nutrition to promote growth, development and methyl donor during methionine metabolism through nutritional reprogramming via regulation of gene expression. Prenatal betaine exposure is reported to modulate hypothalamic cholesterol metabolism in chickens, yet it remains unknown whether feeding hens with betaine-supplemented diet may affect hypothalamic cholesterol metabolism in F1 offspring. In this study, hens were fed with basal or betaine-supplemented (0.5%) for 30days, and the eggs were collected for incubation...
March 2018: Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology
https://www.readbyqxmd.com/read/29192407/de-novo-lipogenesis-and-desaturation-of-fatty-acids-during-adipogenesis-in-bovine-adipose-derived-mesenchymal-stem-cells
#7
Yongli Yue, Lichun Zhang, Xiang Zhang, Xueling Li, Haiquan Yu
Adipose-derived mesenchymal stem cells (ADSCs) are useful cell model to study adipogenesis and energy metabolism. However, the biological characteristics of bovine ADSCs (bADSCs) remain unclear. This study aimed to isolate and identify bADSCs and further investigate fatty acid (FA)-related gene expression and composition of FAs during adipogenesis. The growth curve showed the bADSCs of P5 cells had rapid proliferation superior to P10-P50. The colony formation assay showed colony number of P5 cells was higher than that of P50 cells (51...
January 2018: In Vitro Cellular & Developmental Biology. Animal
https://www.readbyqxmd.com/read/29123635/er-yag-laser-and-cyclosporin-a-effect-on-cell-cycle-regulation-of-human-gingival-fibroblast-cells
#8
Hojjat-Allah Abbaszadeh, Ali Asghar Peyvandi, Yousef Sadeghi, Akram Safaei, Mona Zamanian-Azodi, Maryam Sadat Khoramgah, Mostafa Rezaei-Tavirani
Introduction: Periodontitis is a set of inflammatory disorders characterized by periodontal attachment loss and alveolar bone resorption. Because of deficiency in periodontitis mechanical therapy, this study was aimed to explore the molecular influence of the erbiumdoped: yttrium aluminum garnet (Er:YAG) laser and cyclosporin A (CsA) on human gingival fibroblasts (HGFs) for improvement in periodontal diseases therapy. Methods: We focused on articles that studied the proteome profiles of HGFs after treatment with laser irradiation and application of CsA...
2017: Journal of Lasers in Medical Sciences
https://www.readbyqxmd.com/read/29108233/mitoketoscins-novel-mitochondrial-inhibitors-for-targeting-ketone-metabolism-in-cancer-stem-cells-cscs
#9
Bela Ozsvari, Federica Sotgia, Katie Simmons, Rachel Trowbridge, Richard Foster, Michael P Lisanti
Previous studies have now well-established that epithelial cancer cells can utilize ketone bodies (3-hydroxybutyrate and aceto-acetate) as mitochondrial fuels, to actively promote tumor growth and metastatic dissemination. The two critical metabolic enzymes implicated in this process are OXCT1 and ACAT1, which are both mitochondrial proteins. Importantly, over-expression of OXCT1 or ACAT1 in human breast cancer cells is sufficient to genetically drive tumorigenesis and/or lung metastasis, validating that they indeed behave as metabolic "tumor promoters"...
October 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29097366/quantitative-trait-locus-mapping-of-macrophage-cholesterol-metabolism-and-crispr-cas9-editing-implicate-an-acat1-truncation-as-a-causal-modifier-variant
#10
Qimin Hai, Brian Ritchey, Peggy Robinet, Alexander M Alzayed, Greg Brubaker, Jinying Zhang, Jonathan D Smith
OBJECTIVE: Cholesterol metabolism is a dynamic process involving intracellular trafficking, cholesterol esterification, and cholesterol ester hydrolysis. Our objective was to identify genes that regulate macrophage cholesterol metabolism. APPROACHES AND RESULTS: We performed quantitative trait loci mapping of free and esterified cholesterol levels and the ratio of esterified to free cholesterol in acetylated low-density lipoprotein-loaded bone marrow-derived macrophages from an AKR×DBA/2 strain intercross...
November 2, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29097185/serum-starvation-of-arpe-19-changes-the-cellular-distribution-of-cholesterol-and-fibulin3-in-patterns-reminiscent-of-age-related-macular-degeneration
#11
Dinusha Rajapakse, Katherine Peterson, Sanghamitra Mishra, Graeme Wistow
Retinal pigment epithelium (RPE) has been implicated as key source of cholesterol-rich deposits at Bruch's membrane (BrM) and in drusen in aging human eye. We have shown that serum-deprivation of confluent RPE cells is associated with upregulation of cholesterol synthesis and accumulation of unesterified cholesterol (UC). Here we investigate the cellular processes involved in this response. We compared the distribution and localization of UC and esterified cholesterol (EC); the age-related macular degeneration (AMD) associated EFEMP1/Fibulin3 (Fib3); and levels of acyl-coenzyme A (CoA): cholesterol acyltransferases (ACAT) ACAT1, ACAT2 and Apolipoprotein B (ApoB) in ARPE-19 cells cultured in serum-supplemented and serum-free media...
December 15, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/29026539/the-regulation-of-imf-deposition-in-pectoralis-major-of-fast-and-slow-growing-chickens-at-hatching
#12
Lu Liu, Huanxian Cui, Ruiqi Fu, Maiqing Zheng, Ranran Liu, Guiping Zhao, Jie Wen
BACKGROUND: The lipid from egg yolk is largely consumed in supplying the energy for embryonic growth until hatching. The remaining lipid in the yolk sac is transported into the hatchling's tissues. The gene expression profiles of fast- and slow-growing chickens, Arbor Acres (AA) and Beijing-You (BJY), were determined to identify global differentially expressed genes and enriched pathways related to lipid metabolism in the pectoralis major at hatching. RESULTS: Between these two breeds, the absolute and weight-specific amounts of total yolk energy (TYE) and intramuscular fat (IMF) content in pectoralis major of fast-growing chickens were significantly higher ( P  < 0...
2017: Journal of Animal Science and Biotechnology
https://www.readbyqxmd.com/read/28918429/synergy-of-dendritic-cell-vaccines-and-avasimibe-in-treatment-of-head-and-neck-cancer-in-mice
#13
Xin Chen, Qibin Song, Leiming Xia, Ximing Xu
BACKGROUND The main purpose of this study was to explore the antitumor effect and mechanisms of ACAT1 inhibitor combined with CSCs-DC vaccine. MATERIAL AND METHODS We isolated HNSCC CSCs and gained CSCs antigens, then used CSCs antigens to load dendritic cells (DC) and generated a CSCs-DC vaccine. We treated mice after surgical excision of established SCC7 tumors with CSCs-DC vaccine and/or ACAT1 inhibitor, and recorded local tumor relapse and host survival. T cells and B cells were harvested from mice treated with CSCs-DC vaccine and/or ACAT1 inhibitor...
September 17, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28900085/-expression-of-mir-21-and-its-acat1-armcx1-and-pten-target-genes-in-liver-of-female-rats-treated-with-ddt-and-benzo-a-pyrene
#14
M D Chanyshev, D S Ushakov, L F Gulyaeva
MiR-21 is the most studied cancer-promoting oncomiR, which target numerous tumor suppressor genes associated with proliferation, apoptosis, and invasion. Here we have studied the synthesis of miR-21 and quantified the mRNA and protein levels for miR-21 potential target genes, i.e., Acat1, Armcx1, and Pten, in the livers of female Wistar rats after their treatment with either 1,1-trichloro-2,2-di(4-chlorophenyl)ethane (DDT) or benzo[a]pyrene (BP). The most important finding appears to be the significant decrease in the miR-21 level the day after treatment with DDT with subsequent rebound...
July 2017: Molekuliarnaia Biologiia
https://www.readbyqxmd.com/read/28877685/positive-regulation-of-prostate-cancer-cell-growth-by-lipid-droplet-forming-and-processing-enzymes-dgat1-and-abhd5
#15
Ranjana Mitra, Thuc T Le, Priyatham Gorjala, Oscar B Goodman
BACKGROUND: Neoplastic cells proliferate rapidly and obtain requisite building blocks by reprogramming metabolic pathways that favor growth. Previously, we observed that prostate cancer cells uptake and store lipids in the form of lipid droplets, providing building blocks for membrane synthesis, to facilitate proliferation and growth. Mechanisms of lipid uptake, lipid droplet dynamics and their contribution to cancer growth have yet to be defined. This work is focused on elucidating the prostate cancer-specific modifications in lipid storage pathways so that these modified gene products can be identified and therapeutically targeted...
September 6, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28875337/clinical-and-molecular-analysis-of-6-chinese-patients-with-isoleucine-metabolism-defects-identification-of-3-novel-mutations-in-the-hsd17b10-and-acat1-gene
#16
Ling Su, Xiuzhen Li, Ruizhu Lin, Huiying Sheng, Zhichun Feng, Li Liu
Hydroxysteroid (17β) dehydrogenase 10 (HSD10) and mitochondrial acetoacetyl-CoA thiolase (β-KT) are two adjacent enzymes for the degradation of isoleucine, thus HSD10 and β-KT deficiencies are confusing at an early stage because of nearly the same elevation of typical metabolites in urine, such as 2-methyl-3-hydroxybutyric acid (2M3HBA) and tiglylglycine (TG). In order to better understand the differences between these two disorders, we described the clinical and molecular characteristics of two HSD10 deficiency patients and four β-KT deficiency patients...
December 2017: Metabolic Brain Disease
https://www.readbyqxmd.com/read/28865848/grain-challenge-affects-systemic-and-hepatic-molecular-biomarkers-of-inflammation-stress-and-metabolic-responses-to-a-greater-extent-in-holstein-than-jersey-cows
#17
T Xu, F C Cardoso, A Pineda, E Trevisi, X Shen, F Rosa, J S Osorio, J J Loor
Long-term feeding of high-grain diets to dairy cows often results in systemic inflammation characterized by alterations in acute-phase proteins and other biomarkers, both in plasma and immune-responsive tissues like the liver. The molecular and systemic changes that characterize an acute grain feeding challenge remain unclear. The current study involved 6 Holstein and 6 Jersey cows in a replicated 2 × 2 Latin square. Periods (10 d) were divided into 4 stages (S): S1, d 1 to 3, served as baseline with total mixed ration (TMR) ad libitum; S2, d 4, served as restricted feeding, with cows offered 50% of the average daily intake observed in S1; S3, d 5, a grain challenge was performed, in which cows were fed a TMR ad libitum without (CON) or with an additional pellet wheat-barley (1:1; HIG) at 20% of dry matter intake top-dressed onto the TMR; S4, d 6 to 10, served as recovery during which cows were allowed ad libitum access to the TMR...
November 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28726122/beta-ketothiolase-deficiency-presenting-with-metabolic-stroke-after-a-normal-newborn-screen-in-two-individuals
#18
Monica H Wojcik, Klaas J Wierenga, Lance H Rodan, Inderneel Sahai, Sacha Ferdinandusse, Casie A Genetti, Meghan C Towne, Roy W A Peake, Philip M James, Alan H Beggs, Catherine A Brownstein, Gerard T Berry, Pankaj B Agrawal
Beta-ketothiolase (mitochondrial acetoacetyl-CoA thiolase) deficiency is a genetic disorder characterized by impaired isoleucine catabolism and ketone body utilization that predisposes to episodic ketoacidosis. It results from biallelic pathogenic variants in the ACAT1 gene, encoding mitochondrial beta-ketothiolase. We report two cases of beta-ketothiolase deficiency presenting with acute ketoacidosis and "metabolic stroke." The first patient presented at 28 months of age with metabolic acidosis and pallidal stroke in the setting of a febrile gastrointestinal illness...
July 20, 2017: JIMD Reports
https://www.readbyqxmd.com/read/28689740/clinical-presentation-and-outcome-in-a-series-of-32-patients-with-2-methylacetoacetyl-coenzyme-a-thiolase-mat-deficiency
#19
Sarah Catharina Grünert, Robert Niklas Schmitt, Sonja Marina Schlatter, Corinne Gemperle-Britschgi, Mehmet Cihan Balcı, Volker Berg, Mahmut Çoker, Anibh M Das, Mübeccel Demirkol, Terry G J Derks, Gülden Gökçay, Sema Kalkan Uçar, Vassiliki Konstantopoulou, G Christoph Korenke, Amelie Sophia Lotz-Havla, Andrea Schlune, Christian Staufner, Christel Tran, Gepke Visser, Karl Otfried Schwab, Toshiyuki Fukao, Jörn Oliver Sass
2-methylacetoacetyl-coenzyme A thiolase (MAT) deficiency, also known as beta-ketothiolase deficiency, is an inborn error of ketone body utilization and isoleucine catabolism. It is caused by mutations in the ACAT1 gene and may present with metabolic ketoacidosis. In order to obtain a more comprehensive view on this disease, we have collected clinical and biochemical data as well as information on ACAT1 mutations of 32 patients from 12 metabolic centers in five countries. Patients were between 23months and 27years old, more than half of them were offspring of a consanguineous union...
September 2017: Molecular Genetics and Metabolism
https://www.readbyqxmd.com/read/28550509/possible-involvement-of-acss2-gene-in-alcoholism
#20
Andrea Frozino Ribeiro, Roseli Boerngen de Lacerda, Diego Correia, Ana Lúcia Brunialti-Godard, Débora Marques de Miranda, Valdir Ribeiro Campos, Valéria Fernandes de Souza, Angela Maria Ribeiro
Alcoholism is a psychiatric disorder that composes one of the principal causes of health disabilities in the world population. Furthermore, the available pharmacotherapy is limited. Therefore, this research was carried out to better understand the basis of the underlying neurobiological processes of this disorder and to discover potential therapeutic targets. Real-time PCR analysis was performed in the amygdala nuclei region of the brain of mice exposed to a chronic three-bottle free-choice model (water, 5 and 10% v/v ethanol)...
May 26, 2017: Journal of Neural Transmission
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