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https://www.readbyqxmd.com/read/28199134/genetic-control-of-fatty-acid-%C3%AE-oxidation-in-chronic-obstructive-pulmonary-disease
#1
Zhiqiang Jiang, Nelson H Knudsen, Gang Wang, Weiliang Qiu, Zun Zar Chi Naing, Yan Bai, Xingbin Ai, Chih-Hao Lee, Xiaobo Zhou
Bioenergetics homeostasis is important for cells to sustain normal functions and defend against injury. Genetics controls on bioenergetics homeostasis, especially lipid metabolism remain poorly understood in chronic obstructive pulmonary diseases (COPD), the third leading cause of death in the world. Additionally, biological function of most susceptible genes identified from genome-wide association studies (GWAS) in COPD remains unclear. Here, we aim to address 1) how fatty acid oxidation, specifically β-oxidation (FAO), a key lipid metabolism pathway that provides energy to cells, contributes to cigarette smoke (CS)-induced COPD; and 2) whether and how FAM13A (family with sequence similarity 13 member A), a well-replicated COPD GWAS gene, modulates FAO pathway...
February 15, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28197827/phloretin-prevents-high-fat-diet-induced-obesity-and-improves-metabolic-homeostasis
#2
Sary Alsanea, Mingming Gao, Dexi Liu
Reactive oxygen species generated as a by-product in metabolism play a central role in the development of obesity and obesity-related metabolic complications. The objective of the current study is to explore the possibility to block obesity and improve metabolic homeostasis via phloretin, a natural antioxidant product from apple tree leaves and Manchurian apricot. Both preventive and therapeutic activities of phloretin were assessed using a high-fat diet-induced obesity mouse model. Phloretin was injected intraperitoneally twice weekly into regular and obese mice fed a high-fat diet...
February 14, 2017: AAPS Journal
https://www.readbyqxmd.com/read/28194238/epigenome-wide-association-study-ewas-on-lipids-the-rotterdam-study
#3
Kim V E Braun, Klodian Dhana, Paul S de Vries, Trudy Voortman, Joyce B J van Meurs, Andre G Uitterlinden, Albert Hofman, Frank B Hu, Oscar H Franco, Abbas Dehghan
BACKGROUND: DNA methylation is a key epigenetic mechanism that is suggested to be associated with blood lipid levels. We aimed to identify CpG sites at which DNA methylation levels are associated with blood levels of triglycerides, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and total cholesterol in 725 participants of the Rotterdam Study, a population-based cohort study. Subsequently, we sought replication in a non-overlapping set of 760 participants...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28152052/choline-and-methionine-differentially-alter-methyl-carbon-metabolism-in-bovine-neonatal-hepatocytes
#4
Tawny L Chandler, Heather M White
Intersections in hepatic methyl group metabolism pathways highlights potential competition or compensation of methyl donors. The objective of this experiment was to examine the expression of genes related to methyl group transfer and lipid metabolism in response to increasing concentrations of choline chloride (CC) and DL-methionine (DLM) in primary neonatal hepatocytes that were or were not exposed to fatty acids (FA). Primary hepatocytes isolated from 4 neonatal Holstein calves were maintained as monolayer cultures for 24 h before treatment with CC (61, 128, 2028, and 4528 μmol/L) and DLM (16, 30, 100, 300 μmol/L), with or without a 1 mmol/L FA cocktail in a factorial arrangement...
2017: PloS One
https://www.readbyqxmd.com/read/28139377/cpt1a-methylation-is-associated-with-plasma-adiponectin
#5
S Aslibekyan, A N Do, H Xu, S Li, M R Irvin, D Zhi, H K Tiwari, D M Absher, A R Shuldiner, T Zhang, W Chen, K Tanner, C Hong, B D Mitchell, G Berenson, D K Arnett
BACKGROUND AND AIMS: Adiponectin, an adipose-secreted protein that has been linked to insulin sensitivity, plasma lipids, and inflammatory patterns, is an established biomarker for metabolic health. Despite clinical relevance and high heritability, the determinants of plasma adiponectin levels remain poorly understood. METHODS AND RESULTS: We conducted the first epigenome-wide cross-sectional study of adiponectin levels using methylation data on 368,051 cytosine-phosphate-guanine (CpG) sites in CD4+ T-cells from the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN, n = 991)...
November 23, 2016: Nutrition, Metabolism, and Cardiovascular Diseases: NMCD
https://www.readbyqxmd.com/read/28125087/carnitine-palmitoyltransferase-1a-p479l-and-infant-death-policy-implications-of-emerging-data
#6
REVIEW
Alison E Fohner, Nanibaa' A Garrison, Melissa A Austin, Wylie Burke
Carnitine palmitoyltransferase 1 isoform A (CPT1A) is a crucial enzyme for the transport of long-chain fatty acids into the mitochondria. The CPT1A p.P479L variant is found in high frequencies among indigenous populations residing on the west and north coasts of Alaska and Canada and in northeast Siberia and Greenland. Epidemiological studies have reported a statistical association between P479L homozygosity and infant death in Alaska Native and Canadian Inuit populations. Here, we review the available evidence about the P479L variant and apply to these data the epidemiological criteria for assessing causal associations...
January 26, 2017: Genetics in Medicine: Official Journal of the American College of Medical Genetics
https://www.readbyqxmd.com/read/28121324/lychee-pulp-phenolics-ameliorate-hepatic-lipid-accumulation-by-reducing-mir-33-and-mir-122-expression-in-mice-fed-a-high-fat-diet
#7
Dongxiao Su, Ruifen Zhang, Fangli Hou, Jianwei Chi, Fei Huang, Shijuan Yan, Lei Liu, Yuanyuan Deng, Zhencheng Wei, Mingwei Zhang
Dietary phenolics exhibit hypolipidemic activity by changing lipid metabolism-related microRNA (miRNA) expression. Quercetin 3-O-rutinoside-7-O-α-l-rhamnosidase (quercetin 3-rut-7-rha), rutin and (-)-epicatechin are the main phenolics in lychee (Litchi chinensis Sonn.) pulp. A previous study reported that quercetin 3-rut-7-rha and rutin had hypolipidemic effects. To elucidate these effects and the underlying molecular mechanisms of lychee pulp phenolics (LPPs), the hepatic mRNA and protein expression of lipid metabolism-related genes and their associated miRNAs were measured after ten weeks of treatment with a high-fat diet (HFD) alone or in combination with LPPs...
January 25, 2017: Food & Function
https://www.readbyqxmd.com/read/28101337/adipocyte-lipolysis-links-obesity-to-breast-cancer-growth-adipocyte-derived-fatty-acids-drive-breast-cancer-cell-proliferation-and-migration
#8
Seher Balaban, Robert F Shearer, Lisa S Lee, Michelle van Geldermalsen, Mark Schreuder, Harrison C Shtein, Rose Cairns, Kristen C Thomas, Daniel J Fazakerley, Thomas Grewal, Jeff Holst, Darren N Saunders, Andrew J Hoy
BACKGROUND: Obesity is associated with increased recurrence and reduced survival of breast cancer. Adipocytes constitute a significant component of breast tissue, yet their role in provisioning metabolic substrates to support breast cancer progression is poorly understood. RESULTS: Here, we show that co-culture of breast cancer cells with adipocytes revealed cancer cell-stimulated depletion of adipocyte triacylglycerol. Adipocyte-derived free fatty acids were transferred to breast cancer cells, driving fatty acid metabolism via increased CPT1A and electron transport chain complex protein levels, resulting in increased proliferation and migration...
2017: Cancer & Metabolism
https://www.readbyqxmd.com/read/28095627/melatonin-regulates-lipid-metabolism-in-porcine-oocytes
#9
Jun-Xue Jin, Sanghoon Lee, Anukul Taweechaipaisankul, Geon A Kim, Byeong Chun Lee
It is being increasingly recognized that the processes of lipogenesis and lipolysis are important for providing an essential energy source during oocyte maturation and embryo development. Recent studies demonstrated that melatonin has a role in lipid metabolism regulation, including lipogenesis, lipolysis and mitochondrial biogenesis. In this study, we attempted to investigate the effects of melatonin on lipid metabolism during porcine oocyte in vitro maturation. Melatonin treatment significantly enhanced the number of lipid droplets (LDs) and upregulated gene expression related to lipogenesis (ACACA, FASN, PPARγ, and SREBF1)...
January 17, 2017: Journal of Pineal Research
https://www.readbyqxmd.com/read/28069424/different-regulation-of-insulin-on-glucose-and-lipid-metabolism-in-2-strains-of-gibel-carp
#10
Junyan Jin, Xiaoming Zhu, Dong Han, Yunxia Yang, Haokun Liu, Shouqi Xie
To test the hypothesis that response to insulin by regulating glucose and lipid metabolism in gibel carp A strain may be different from that in DT strain, bovine insulin was injected into both strains of gibel carp after previous fasting for 48 h. The results showed that insulin induced hypoglycemia at 3 h in 2 strains, and that this was coupled with increased expression of glucose transporters (GLUT2 in the liver and GLUT1, GLUT4 in the muscle) and glycolytic enzyme (HK2 in the muscle) in both strains. Insulin induced increased glycolysis (GK) and fatty acid oxidation (ACO3 in the liver and CPT1a, ACO3 in the muscle) in the DT strain...
January 6, 2017: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/28049638/leukemic-blasts-program-bone-marrow-adipocytes-to-generate-a-pro-tumoral-microenvironment
#11
Manar S Shafat, Thomas Oellerich, Sebastian Mohr, Stephen D Robinson, Dylan R Edwards, Christopher R Marlein, Rachel E Piddock, Matthew Fenech, Lyubov Zaitseva, Amina Abdul-Aziz, Jeremy Turner, Johnathan A Watkins, Matthew Lawes, Kristian M Bowles, Stuart A Rushworth
Despite currently available therapies most patients diagnosed with acute myeloid leukemia (AML) die of their disease. Tumor-host interactions are critical for the survival and proliferation of cancer cells; accordingly, we hypothesise that specific targeting of the tumor microenvironment may constitute an alternative or additional strategy to conventional tumor-directed chemotherapy. Since adipocytes have been shown to promote breast and prostate cancer proliferation, and because the bone marrow adipose tissue (MAT) accounts for up to 70% of bone marrow volume in adult humans, we examined the adipocyte-leukaemia cell interactions to determine if they are essential for the growth and survival of AML...
January 3, 2017: Blood
https://www.readbyqxmd.com/read/28024299/the-role-of-fatty-acid-%C3%AE-oxidation-in-lymphangiogenesis
#12
Brian W Wong, Xingwu Wang, Annalisa Zecchin, Bernard Thienpont, Ivo Cornelissen, Joanna Kalucka, Melissa García-Caballero, Rindert Missiaen, Hongling Huang, Ulrike Brüning, Silvia Blacher, Stefan Vinckier, Jermaine Goveia, Marlen Knobloch, Hui Zhao, Cathrin Dierkes, Chenyan Shi, René Hägerling, Veronica Moral-Dardé, Sabine Wyns, Martin Lippens, Sebastian Jessberger, Sarah-Maria Fendt, Aernout Luttun, Agnès Noel, Friedemann Kiefer, Bart Ghesquière, Lieve Moons, Luc Schoonjans, Mieke Dewerchin, Guy Eelen, Diether Lambrechts, Peter Carmeliet
Lymphatic vessels are lined by lymphatic endothelial cells (LECs), and are critical for health. However, the role of metabolism in lymphatic development has not yet been elucidated. Here we report that in transgenic mouse models, LEC-specific loss of CPT1A, a rate-controlling enzyme in fatty acid β-oxidation, impairs lymphatic development. LECs use fatty acid β-oxidation to proliferate and for epigenetic regulation of lymphatic marker expression during LEC differentiation. Mechanistically, the transcription factor PROX1 upregulates CPT1A expression, which increases acetyl coenzyme A production dependent on fatty acid β-oxidation...
December 26, 2016: Nature
https://www.readbyqxmd.com/read/28007964/peroxisome-proliferator-activated-receptor-%C3%AE-accelerates-%C3%AE-chlorofatty-acid-catabolism
#13
Elisa N D Palladino, Wen-Yi Wang, Carolyn J Albert, Cédric Langhi, Ángel Baldán, David A Ford
α-Chlorofatty aldehydes are generated from myeloperoxidase-derived HOCl targeting plasmalogens, and are subsequently oxidized to α-chlorofatty acids (α-ClFAs). The catabolic pathway for α-ClFA is initiated by ω-oxidation. Here, we examine PPAR-α activation as a mechanism to increase α-ClFA catabolism. Pretreating both HepG2 cells and primary mouse hepatocytes with the PPAR-α agonist, pirinixic acid (Wy 14643), increased the production of α-chlorodicarboxylic acids (α-ClDCAs) in cells treated with exogenous α-ClFA...
February 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/27968834/methylation-loci-associated-with-body-mass-index-waist-circumference-and-waist-to-hip-ratio-in-chinese-adults-an-epigenome-wide-analysis
#14
Biqi Wang, Wenjing Gao, Jun Li, Canqing Yu, Weihua Cao, Jun Lv, Zengchang Pang, Liming Cong, Hua Wang, Xianping Wu, Liming Liang, Tangchun Wu, Liming Li
BACKGROUND: DNA methylation has been implicated in the pathology of obesity, but little is known about such epigenetic variants in Chinese people. We conducted an epigenome-wide analysis of methylation at CpG sites in relation to body mass index (BMI), waist circumference (WC) and waist-to-hip ratio (WHR) among Chinese adult populations. METHODS: 469 twins from the Chinese National Twin Registry were the discovery cohort. After quality control, methylation levels in whole blood leukocyte DNA were tested for association with BMI, WC, and WHR using mixed linear regressions, adjusting for demographics, lifestyle, and family structure...
October 2016: Lancet
https://www.readbyqxmd.com/read/27956176/glucagon-like-peptide-1-effects-lipotoxic-oxidative-stress-by-regulating-the-expression-of-micrornas
#15
Zhiying Zhang, Huifang Liu, Qiang Li
Aim to confirm whether the treatment of GLP-1 can modulated body weight, lipid metabolism, insulin content, pancreas oxidative stress, improved T-AOC, MDA levels related to FFA-Induced oxidative stress in C57BL/6 mice and INS-1 cells. In this study, GLP-1 makes the expression of AMPK, PPARα, CPT1A and SIRT1 increased, and the expression of SREBP1c, miR-33 and miR-370 decreased. Interestingly, the effects of GLP-1 were less dose dependent as GLP-1 regulated the FFA, which related to gene expression at much lower doses (3 μg/kg, 10 mM, mice and INS-1 respectively) and effects were relatively maintained at higher dose (30 μg/kg, 100 mM, mice and INS-1 respectively) as well...
January 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27916548/high-expression-of-cpt1a-predicts-adverse-outcomes-a-potential-therapeutic-target-for-acute-myeloid-leukemia
#16
Jinlong Shi, Huaping Fu, Zhilong Jia, Kunlun He, Lin Fu, Weidong Wang
Carnitine palmitoyl transferase 1A (CPT1A) protein catalyzes the rate-limiting step of Fatty-acid oxidation (FAO) pathway, which can promote cell proliferation and suppress apoptosis. Targeting CPT1A has shown remarkable anti-leukemia activity. But, its prognostic value remains unclear in Acute Myeloid Leukemia (AML). In two independent cohorts of cytogenetically normal AML (CN-AML) patients, compared to low expression of CPT1A (CPT1A(low)), high expression of CPT1A (CPT1A(high)) was significantly associated with adverse outcomes, which was also shown in European Leukemia Network (ELN) Intermediate-I category...
December 2016: EBioMedicine
https://www.readbyqxmd.com/read/27885970/cpt1a-gene-expression-in-peripheral-blood-mononuclear-cells-as-an-early-biomarker-of-diet-related-metabolic-alterations
#17
Rubén Díaz-Rúa, Andreu Palou, Paula Oliver
BACKGROUND: Research on biomarkers that provide early information about the development of future metabolic alterations is an emerging discipline. Gene expression analysis in peripheral blood mononuclear cells (PBMC) is a promising tool to identify subjects at risk of developing diet-related diseases. OBJECTIVE: We analysed PBMC expression of key energy homeostasis-related genes in a time-course analysis in order to find out early markers of metabolic alterations due to sustained intake of high-fat (HF) and high-protein (HP) diets...
2016: Food & Nutrition Research
https://www.readbyqxmd.com/read/27873461/human-peripheral-blood-mononuclear-cell-in-vitro-system-to-test-the-efficacy-of-food-bioactive-compounds-effects-of-polyunsaturated-fatty-acids-and-their-relation-with-bmi
#18
Margalida Cifre, Rubén Díaz-Rúa, Rubén Varela-Calviño, Bàrbara Reynés, Jordi Pericás-Beltrán, Andreu Palou, Paula Oliver
SCOPE: To analyse the usefulness of isolated human peripheral blood mononuclear cells (PBMC) to rapidly/easily reflect n-3 long-chain polyunsaturated fatty acid (LCPUFA) effects on lipid metabolism/inflammation gene profile, and evaluate if these effects are body mass index (BMI) dependent. METHODS AND RESULTS: PBMC from normoweight (NW) and overweight/obese (OW/OB) subjects were incubated with physiological doses of docosahexaenoic (DHA), eicosapentaenoic acid (EPA), or their combination...
November 22, 2016: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/27865496/peroxisome-proliferator-activated-receptor-delta-facilitates-lipid-secretion-and-catabolism-of-fatty-acids-in-dairy-goat-mammary-epithelial-cells
#19
H B Shi, C H Zhang, W Zhao, J Luo, J J Loor
In rodents, peroxisome proliferator-activated receptor delta (PPARD) is associated primarily with catabolism of fatty acids. However, the role of PPARD in regulating lipid metabolism in ruminant mammary gland remains unknown. In the present study, we assessed the mRNA abundance of PPARD at 3 stages of lactation in goat mammary tissue. Results revealed that PPARD had lower expression at peak lactation than in the nonlactating period. Luciferase assays revealed that GW0742 (GW), a specific PPARD ligand, enhanced the activity of the PPARD response element in goat mammary epithelial cells...
January 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/27832201/role-of-hypothalamic-creb-binding-protein-in-obesity-and-molecular-reprogramming-of-metabolic-substrates
#20
Cesar L Moreno, Linda Yang, Penny A Dacks, Fumiko Isoda, Jan M A van Deursen, Charles V Mobbs
We have reported a correlation between hypothalamic expression of Creb-binding protein (Cbp) and lifespan, and that inhibition of Cbp prevents protective effects of dietary restriction during aging, suggesting that hypothalamic Cbp plays a role in responses to nutritional status and energy balance. Recent GWAS and network analyses have also implicated Cbp as the most connected gene in protein-protein interactions in human Type 2 diabetes. The present studies address mechanisms mediating the role of Cbp in diabetes by inhibiting hypothalamic Cbp using a Cre-lox strategy...
2016: PloS One
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