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CPT1A

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https://www.readbyqxmd.com/read/27885970/cpt1a-gene-expression-in-peripheral-blood-mononuclear-cells-as-an-early-biomarker-of-diet-related-metabolic-alterations
#1
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
#2
Margalida Cifre, Rubén Díaz-Rúa, Rubén Varela-Calviño, Bàrbara Reynés, Jordi Pericás-Beltrán, Andreu Palou, Paula Oliver
SCOPE: To analyse 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 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
#3
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...
November 16, 2016: Journal of Dairy Science
https://www.readbyqxmd.com/read/27832201/role-of-hypothalamic-creb-binding-protein-in-obesity-and-molecular-reprogramming-of-metabolic-substrates
#4
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
#5
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
#6
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...
October 25, 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
#7
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
#8
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
#9
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
#10
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
#11
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...
September 30, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27634649/identification-and-validation-of-seven-new-loci-showing-differential-dna-methylation-related-to-serum-lipid-profile-an-epigenome-wide-approach-the-regicor-study
#12
S Sayols-Baixeras, I Subirana, C Lluis-Ganella, F Civeira, J Roquer, A N Do, D Absher, D Muñoz, C Soriano-Tárraga, J Jiménez-Conde, J Ordovas, M Senti, S Aslibekyan, J Marrugat, D K Arnett, R Elosua
Lipid traits (total, low-density and high-density lipoprotein cholesterol, and triglycerides) are risk factors for cardiovascular disease. DNA methylation is an inherited but also modifiable epigenetic mark that has been related to cardiovascular risk factors. Our aim was to identify loci showing differential DNA methylation related to serum lipid levels. Blood DNA methylation was assessed using the Illumina HumanMethylation450 BeadChip. A two-stage epigenome-wide association study was performed, with a discovery sample in the REGICOR study (n=645) and validation in the Framingham Offspring Study (n=2,542)...
September 15, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/27573054/jatrorrhizine-hydrochloride-attenuates-hyperlipidemia-in-a-high-fat-diet-induced-obesity-mouse-model
#13
Weiwei Yang, Liping She, Kun Yu, Shan Yan, Xuefeng Zhang, Xiaoyi Tian, Shuren Ma, Xiwen Zhang
Jatrorrhizine hydrochloride (JH) is an active component of the traditional Chinese herb Coptis chinensis, which has been used to prevent and treat metabolic disorders. Hyperlipidemia is one of the principal factors underlying numerous metabolic diseases, including diabetes and obesity. Therefore, the aim of the present study was to investigate the lipid lowering effects of JH treatment in vivo in an obesity mouse model. JH-treated hyperlipidemic mice exhibited a reduction in body weight, as well as improved glucose tolerance and insulin sensitivity...
October 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27563814/molecular-regulation-of-apoptotic-machinery-and-lipid-metabolism-by-mtorc1-mtorc2-dual-inhibitors-in-preclinical-models-of-her2-pik3camut-breast-cancer
#14
Jianchang Qian, Yaqing Chen, Tao Meng, Lanping Ma, Lanfang Meng, Xin Wang, Ting Yu, Arie Zask, Jingkang Shen, Ker Yu
The mechanistic target of rapamycin (mTOR) is a rational target for cancer treatment. While the mTORC1-selective rapalogs have shown significant benefits in the clinic, antitumor response may be further improved by inhibiting both mTORC1 and mTORC2. Herein, we established target profile of a novel mTOR kinase inhibitor (mTOR-KI) MTI-31 and employed it to study new therapeutic mechanism in breast cancer. MTI-31 demonstrated a potent mTOR binding affinity with >5000 fold selectivity over the related PI3K family isoforms...
August 22, 2016: Oncotarget
https://www.readbyqxmd.com/read/27488889/dietary-thylakoids-reduce-visceral-fat-mass-and-increase-expression-of-genes-involved-in-intestinal-fatty-acid-oxidation-in-high-fat-fed-rats
#15
Eva-Lena Stenblom, Emil Egecioglu, Caroline Montelius, Deepti Ramachandran, Britta Bonn, Björn Weström, Abdelhak Mansouri, Wolfgang Langhans, Charlotte Erlanson-Albertsson
Thylakoids reduce body weight gain and body fat accumulation in rodents. This study investigated whether an enhanced oxidation of dietary fat-derived fatty acids in the intestine contributes to the thylakoid effects. Male Sprague-Dawley rats were fed a high-fat diet with (n = 8) or without thylakoids (n = 8) for 2 wk. Body weight, food intake, and body fat were measured, and intestinal mucosa was collected and analyzed. Quantitative real-time PCR was used to measure gene expression levels of key enzymes involved in fatty acid transport, fatty acid oxidation, and ketogenesis...
September 1, 2016: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/27474977/the-effect-of-increasing-concentrations-of-dl-methionine-and-2-hydroxy-4-methylthio-butanoic-acid-on-hepatic-genes-controlling-methionine-regeneration-and-gluconeogenesis
#16
Qian Zhang, Sandra J Bertics, N Daniel Luchini, Heather M White
Metabolizable methionine (Met) concentrations can be increased by feeding rumen-protected dl-Met or the isopropyl ester of 2-hydroxy-4-(methylthio) butanoic acid (HMBi). Hepatic responses to increasing concentrations of metabolizable Met as a result of supplementation of different Met sources have not been comparatively examined. The objective of this experiment was to examine the regulation of key genes for Met metabolism, gluconeogenesis, and fatty acid oxidation in response to increasing concentrations of dl-Met or 2-hydroxy-4-(methylthio) butanoic acid (HMB) in bovine primary hepatocytes...
October 2016: Journal of Dairy Science
https://www.readbyqxmd.com/read/27455510/nox4-dependent-fatty-acid-oxidation-promotes-nlrp3-inflammasome-activation-in-macrophages
#17
Jong-Seok Moon, Kiichi Nakahira, Kuei-Pin Chung, Gina M DeNicola, Michael Jakun Koo, Maria A Pabón, Kristen T Rooney, Joo-Heon Yoon, Stefan W Ryter, Heather Stout-Delgado, Augustine M K Choi
Altered metabolism has been implicated in the pathogenesis of inflammatory diseases. NADPH oxidase 4 (NOX4), a source of cellular superoxide anions, has multiple biological functions that may be of importance in inflammation and in the pathogenesis of human metabolic diseases, including diabetes. However, the mechanisms by which NOX4-dependent metabolic regulation affect the innate immune response remain unclear. Here we show that deficiency of NOX4 resulted in reduced expression of carnitine palmitoyltransferase 1A (CPT1A), which is a key mitochondrial enzyme in the fatty acid oxidation (FAO) pathway...
September 2016: Nature Medicine
https://www.readbyqxmd.com/read/27438137/carnitine-palmitoyltransferase-1-increases-lipolysis-ucp1-protein-expression-and-mitochondrial-activity-in-brown-adipocytes
#18
María Calderon-Dominguez, David Sebastián, Raquel Fucho, Minéia Weber, Joan F Mir, Ester García-Casarrubios, María Jesús Obregón, Antonio Zorzano, Ángela M Valverde, Dolors Serra, Laura Herrero
The discovery of active brown adipose tissue (BAT) in adult humans and the fact that it is reduced in obese and diabetic patients have put a spotlight on this tissue as a key player in obesity-induced metabolic disorders. BAT regulates energy expenditure through thermogenesis; therefore, harnessing its thermogenic fat-burning power is an attractive therapeutic approach. We aimed to enhance BAT thermogenesis by increasing its fatty acid oxidation (FAO) rate. Thus, we expressed carnitine palmitoyltransferase 1AM (CPT1AM), a permanently active mutant form of CPT1A (the rate-limiting enzyme in FAO), in a rat brown adipocyte (rBA) cell line through adenoviral infection...
2016: PloS One
https://www.readbyqxmd.com/read/27376874/genomics-of-human-fatty-liver-disease-reveal-mechanistically-linked-lipid-droplet-associated-gene-regulations-in-blunt-steatosis-and-nonalcoholic-steatohepatitis
#19
Nishika Sahini, Jürgen Borlak
Nonalcoholic fatty liver disease (NAFLD) is a common disorder hallmarked by excessive lipid deposits. Based on our recent research on lipid droplet (LD) formation in hepatocytes, we investigated LD-associated gene regulations in NAFLD of different grades, that is, steatosis vs steatohepatitis by comparing liver biopsies from healthy controls (N = 13) and NAFLD patients (N = 102). On average, more than 700 differentially expressed genes (DEGs) were identified of which 146 are mechanistically linked to LD formation...
June 16, 2016: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/27350042/blood-lipids-influence-dna-methylation-in-circulating-cells
#20
Koen F Dekkers, Maarten van Iterson, Roderick C Slieker, Matthijs H Moed, Marc Jan Bonder, Michiel van Galen, Hailiang Mei, Daria V Zhernakova, Leonard H van den Berg, Joris Deelen, Jenny van Dongen, Diana van Heemst, Albert Hofman, Jouke J Hottenga, Carla J H van der Kallen, Casper G Schalkwijk, Coen D A Stehouwer, Ettje F Tigchelaar, André G Uitterlinden, Gonneke Willemsen, Alexandra Zhernakova, Lude Franke, Peter A C 't Hoen, Rick Jansen, Joyce van Meurs, Dorret I Boomsma, Cornelia M van Duijn, Marleen M J van Greevenbroek, Jan H Veldink, Cisca Wijmenga, Erik W van Zwet, P Eline Slagboom, J Wouter Jukema, Bastiaan T Heijmans
BACKGROUND: Cells can be primed by external stimuli to obtain a long-term epigenetic memory. We hypothesize that long-term exposure to elevated blood lipids can prime circulating immune cells through changes in DNA methylation, a process that may contribute to the development of atherosclerosis. To interrogate the causal relationship between triglyceride, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol levels and genome-wide DNA methylation while excluding confounding and pleiotropy, we perform a stepwise Mendelian randomization analysis in whole blood of 3296 individuals...
2016: Genome Biology
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