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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
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
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
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
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
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
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
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
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
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
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
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
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
Mette Korre Andersen, Emil Jørsboe, Camilla Helene Sandholt, Niels Grarup, Marit Eika Jørgensen, Nils Joakim Færgeman, Peter Bjerregaard, Oluf Pedersen, Ida Moltke, Torben Hansen, Anders Albrechtsen
Fatty acids (FAs) are involved in cellular processes important for normal body function, and perturbation of FA balance has been linked to metabolic disturbances, including type 2 diabetes. An individual's level of FAs is affected by diet, lifestyle, and genetic variation. We aimed to improve the understanding of the mechanisms and pathways involved in regulation of FA tissue levels, by identifying genetic loci associated with inter-individual differences in erythrocyte membrane FA levels. We assessed the levels of 22 FAs in the phospholipid fraction of erythrocyte membranes from 2,626 Greenlanders in relation to single nucleotide polymorphisms genotyped on the MetaboChip or imputed...
June 2016: PLoS Genetics
Michael J Salini, Nicholas M Wade, Bruno C Araújo, Giovanni M Turchini, Brett D Glencross
A two part experiment was conducted to assess the response of barramundi (Lates calcarifer; initial weight = 10.3 ± 0.03 g; mean ± S.D.) fed one of five diets with varying eicosapentaenoic acid (diets 1, 5, 10, 15 and 20 g/kg) or one of four diets with varying arachidonic acid (1, 6, 12, 18 g/kg) against a fish oil control diet. After 6 weeks of feeding, the addition of EPA or ARA did not impact on growth performance or feed utilisation. Analysis of the whole body fatty acids showed that these reflected those of the diets...
August 2016: Lipids
Yun-Soo Seo, Mi-Yae Shon, Ryong Kong, Ok-Hwa Kang, Tian Zhou, Do-Yeon Kim, Dong-Yeul Kwon
ETHNOPHARMACOLOGICAL RELEVANCE: Ginseng (Panax ginseng C. A. Meyer, Araliaceae) has been used as a traditional medicine for thousands of years for the treatment of a wide variety of diseases, including diabetes. Processed ginseng named Black ginseng exhibits more potent biological activities than white and red ginseng. The aim of this study was to investigate the effects of black ginseng extract (GBG05-FF) on hyperglycemia and glucose tolerance in streptozotocin (STZ)-induced diabetic mice...
August 22, 2016: Journal of Ethnopharmacology
Mien-Cheng Chen, Jen-Ping Chang, Yu-Sheng Lin, Kuo-Li Pan, Wan-Chun Ho, Wen-Hao Liu, Tzu-Hao Chang, Yao-Kuang Huang, Chih-Yuan Fang, Chien-Jen Chen
BACKGROUND: Differentially expressed genes in the left atria of mitral regurgitation (MR) pigs have been linked to peroxisome proliferator-activated receptor (PPAR) signaling pathway in the KEGG pathway. However, specific genes of the PPAR signaling pathway in the left atria of MR patients have never been explored. METHODS: This study enrolled 15 MR patients with heart failure, 7 patients with aortic valve disease and heart failure, and 6 normal controls. We used PCR assay (84 genes) for PPAR pathway and quantitative RT-PCR to study specific genes of the PPAR pathway in the left atria...
2016: Journal of Translational Medicine
Wei Li, Bo Li, Jiaqi Lv, Li Dong, Lili Zhang, Tian Wang
The objective of this study was to investigate the effects of dietary choline supplementation on hepatic lipid metabolism and gene expression in finishing pigs with intrauterine growth retardation (IUGR). Using a 2 × 2 factorial design, eight normal birth weight (NBW) and eight IUGR weaned pigs were fed either a basal diet (NBW pigs fed a basal diet, NC; IUGR pigs fed a basal diet, IC) or a diet supplemented with two times more choline than the basal diet (NBW pigs fed a high-choline diet, NH; IUGR pigs fed a high-choline diet, IH) until 200 d of age...
May 22, 2016: Asian-Australasian Journal of Animal Sciences
C B Jacometo, Z Zhou, D Luchini, E Trevisi, M N Corrêa, J J Loor
In nonruminants, nutrition during pregnancy can program offspring development, metabolism, and health in later life. Rumen-protected Met (RPM) supplementation during the prepartum period improves liver function and immune response in dairy cows. Our aim was to investigate the effects of RPM during late pregnancy on blood biomarkers (23 targets) and the liver transcriptome (24 genes) in neonatal calves from cows fed RPM at 0.08% of diet dry matter/d (MET) for the last 21 d before calving or controls (CON). Blood (n=12 calves per diet) was collected at birth before receiving colostrum (baseline), 24 h after receiving colostrum, 14, 28, and 50 d (post-weaning) of age...
August 2016: Journal of Dairy Science
Sonja M Kessler, Stephan Laggai, Elien Van Wonterg, Katja Gemperlein, Rolf Müller, Johannes Haybaeck, Roosmarijn E Vandenbroucke, Manfred Ogris, Claude Libert, Alexandra K Kiemer
Although insulin-like growth factor 2 (IGF2) has been reported to be overexpressed in steatosis and steatohepatitis, a causal role of IGF2 in steatosis development remains elusive. Aim of our study was to decipher the role of IGF2 in steatosis development. Hydrodynamic gene delivery of an Igf2 plasmid used for transient Igf2 overexpression employing codon-optimized plasmid DNA resulted in a strong induction of hepatic Igf2 expression. The exogenously delivered Igf2 had no influence on endogenous Igf2 expression...
2016: Frontiers in Physiology
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