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CPT1A

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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
#1
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
#2
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
#3
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
#4
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
#5
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
#6
Elisa N D Palladino, Wen-Yi Wang, Carolyn J Albert, Cedric Langhi, Ángel Baldán, David A Ford
α-Chlorofatty aldehydes are generated from myeloperoxidase (MPO)-derived HOCl targeting plasmalogens, and are subsequently oxidized to α-chlorofatty acids (α-ClFA). The catabolic pathway for α-ClFA is initiated by ω-oxidation. Here we examine peroxisome proliferator-activated receptor-α; (PPAR-α) activation as a mechanism to increase α-ClFA catabolism. Pretreating both HepG2 cells and primary mouse hepatocytes with the PPAR-α agonist Wy 14643 increased the production of α-chlorodicarboxylic acids (α-ClDCA) in cells treated with exogenous α-ClFA...
December 22, 2016: 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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
https://www.readbyqxmd.com/read/27809262/benzene-exposure-alters-expression-of-enzymes-involved-in-fatty-acid-%C3%AE-oxidation-in-male-c3h-he-mice
#14
Rongli Sun, Meng Cao, Juan Zhang, Wenwen Yang, Haiyan Wei, Xing Meng, Lihong Yin, Yuepu Pu
Benzene is a well-known hematotoxic carcinogen that can cause leukemia and a variety of blood disorders. Our previous study indicated that benzene disturbs levels of metabolites in the fatty acid β-oxidation (FAO) pathway, which is crucial for the maintenance and function of hematopoietic and leukemic cells. The present research aims to investigate the effects of benzene on changes in the expression of key enzymes in the FAO pathway in male C3H/He mice. Results showed that benzene exposure caused reduced peripheral white blood cell (WBC), red blood cell (RBC), platelet (Pit) counts, and hemoglobin (Hgb) concentration...
October 31, 2016: International Journal of Environmental Research and Public Health
https://www.readbyqxmd.com/read/27793752/targeting-cpt1a-enhances-metabolic-therapy-in-human-melanoma-cells-with-the-braf-v600e-mutation
#15
Gi-Jun Sung, Hyo-Kyoung Choi, Sungmin Kwak, Ji-Hye Song, Hyeonseok Ko, Ho-Geun Yoon, Hee-Bum Kang, Kyung-Chul Choi
Cancer cells are characterized by altered metabolic processes. Recent evidence of metabolic alterations has indicated that the fatty acid oxidation (FAO) pathway is used as a carbon source for anabolic processes in some tumors, thus making this pathway a potential target for therapy. The carnitine palmitoyltransferase (CPT; EC 2.3.1.21) enzyme transfers long-chain fatty acids from the cytosol to the mitochondrial matrix for β-oxidation. Because carnitine palmitoyl transferase 1a (CPT1a) is the rate-limiting enzyme for FAO, the authors evaluated the effects of CPT1A knock-down in BRAF V600E melanoma cell lines...
December 2016: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/27777315/epigenome-wide-association-study-of-triglyceride-postprandial-responses-to-a-high-fat-dietary-challenge
#16
Chao-Qiang Lai, Mary K Wojczynski, Laurence D Parnell, Bertha A Hidalgo, Marguerite Ryan Irvin, Stella Aslibekyan, Michael A Province, Devin M Absher, Donna K Arnett, José M Ordovás
Postprandial lipemia (PPL), the increased plasma TG concentration after consuming a high-fat meal, is an independent risk factor for CVD. Individual responses to a meal high in fat vary greatly, depending on genetic and lifestyle factors. However, only a few loci have been associated with TG-PPL response. Heritable epigenomic changes may be significant contributors to the unexplained inter-individual PPL variability. We conducted an epigenome-wide association study on 979 subjects with DNA methylation measured from CD4(+) T cells, who were challenged with a high-fat meal as a part of the Genetics of Lipid Lowering Drugs and Diet Network study...
December 2016: Journal of Lipid Research
https://www.readbyqxmd.com/read/27746199/the-role-of-dna-methylation-in-dyslipidaemia-a-systematic-review
#17
REVIEW
Kim V E Braun, Trudy Voortman, Klodian Dhana, Jenna Troup, Wichor M Bramer, John Troup, Rajiv Chowdhury, Abbas Dehghan, Taulant Muka, Oscar H Franco
Epigenetic mechanisms, including DNA methylation and histone modifications, might be involved in the regulation of blood lipid concentration variability and may thereby affect cardiovascular health. We aimed to systematically review studies investigating the association between epigenetic marks and plasma concentrations of triacylglycerol, total cholesterol, low-density lipoprotein-cholesterol, and high-density lipoprotein-cholesterol. Six medical databases were searched until September 3rd 2015, reference lists were screened, and experts in the field were contacted...
October 13, 2016: Progress in Lipid Research
https://www.readbyqxmd.com/read/27734926/bone-marrow-derived-and-peritoneal-macrophages-have-different-inflammatory-response-to-oxldl-and-m1-m2-marker-expression-implications-for-atherosclerosis-research
#18
Line S Bisgaard, Christina K Mogensen, Alexander Rosendahl, Helena Cucak, Lars Bo Nielsen, Salka E Rasmussen, Tanja X Pedersen
Macrophages are heterogeneous and can polarize into specific subsets, e.g. pro-inflammatory M1-like and re-modelling M2-like macrophages. To determine if peritoneal macrophages (PEMs) or bone marrow derived macrophages (BMDMs) resembled aortic macrophages from ApoE-/- mice, their M1/M2 phenotype, inflammatory status, and lipid metabolism signatures were compared. oxLDL accumulation was similar in PEMs and BMDMs. On protein expression level, BMDMs showed an M2-like CD206(high)CD11c(low) profile, while cholesterol loading led to enhanced CD11c expression and reduced MCP-1 secretion...
October 13, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27698954/korean-pine-nut-oil-replacement-decreases-intestinal-lipid-uptake-while-improves-hepatic-lipid-metabolism-in-mice
#19
Shuang Zhu, Soyoung Park, Yeseo Lim, Sunhye Shin, Sung Nim Han
BACKGROUND/OBJECTIVES: Consumption of pine nut oil (PNO) was shown to reduce weight gain and attenuate hepatic steatosis in mice fed a high-fat diet (HFD). The aim of this study was to examine the effects of PNO on both intestinal and hepatic lipid metabolism in mice fed control or HFD. MATERIALS/METHODS: Five-week-old C57BL/6 mice were fed control diets containing 10% energy fat from either Soybean Oil (SBO) or PNO, or HFD containing 15% energy fat from lard and 30% energy fat from SBO or PNO for 12 weeks...
October 2016: Nutrition Research and Practice
https://www.readbyqxmd.com/read/27697477/lysophosphatidylcholines-activate-ppar%C3%AE-and-protect-human-skeletal-muscle-cells-from-lipotoxicity
#20
Christian Klingler, Xinjie Zhao, Till Adhikary, Jia Li, Guowang Xu, Hans-Ulrich Häring, Erwin Schleicher, Rainer Lehmann, Cora Weigert
Metabolomics studies of human plasma demonstrate a correlation of lower plasma lysophosphatidylcholines (LPC) concentrations with insulin resistance, obesity, and inflammation. This relationship is not unraveled on a molecular level. Here we investigated the effects of the abundant LPC(16:0) and LPC(18:1) on human skeletal muscle cells differentiated to myotubes. Transcriptome analysis of human myotubes treated with 10μM LPC for 24h revealed enrichment of up-regulated peroxisome proliferator-activated receptor (PPAR) target transcripts, including ANGPTL4, PDK4, PLIN2, and CPT1A...
December 2016: Biochimica et Biophysica Acta
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