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metabolomics AND obesity

Arwen W Gao, Mark G Sterken, Jelmi Uit de Bos, Jelle van Creij, Rashmi Kamble, Basten L Snoek, Jan E Kammenga, Riekelt H Houtkooper
Metabolic homeostasis is sustained by complex biological networks that respond to nutrient availability. Genetic and environmental factors may disrupt this equilibrium, leading to metabolic disorders, including obesity and type 2 diabetes. To identify the genetic factors controlling metabolism, we performed quantitative genetic analysis using a population of 199 recombinant inbred lines (RILs) in the nematode Caenorhabditis elegans We focused on the genomic regions that control metabolite levels by measuring fatty acid (FA) and amino acid (AA) composition in the RILs using targeted metabolomics...
August 14, 2018: Genome Research
Limei Wu, Surya Amarachintha, Jian Xu, Frank Oley, Wei Du
The bone marrow (BM) microenvironment (niche) plays important roles in supporting normal/abnormal haematopoiesis. We investigated the interaction between leukaemic mesenchymal niche and haematopoietic stem and progenitor cells (HSPCs) using the model of Fanconi anaemia (FA), a genetic disorder characterized by BM failure and leukaemia. Healthy donor HSPCs co-cultured on mesenchymal stromal cells (MSCs) derived from FA patients with acute myeloid leukaemia (AML) exhibited higher human engraftment and myeloid expansion in Non-obese diabetic severe combined immunodeficiency IL-2γ-/- /SGM3 recipients...
August 14, 2018: British Journal of Haematology
Qin Yang, Archana Vijayakumar, Barbara B Kahn
The cause of insulin resistance in obesity and type 2 diabetes mellitus (T2DM) is not limited to impaired insulin signalling but also involves the complex interplay of multiple metabolic pathways. The analysis of large data sets generated by metabolomics and lipidomics has shed new light on the roles of metabolites such as lipids, amino acids and bile acids in modulating insulin sensitivity. Metabolites can regulate insulin sensitivity directly by modulating components of the insulin signalling pathway, such as insulin receptor substrates (IRSs) and AKT, and indirectly by altering the flux of substrates through multiple metabolic pathways, including lipogenesis, lipid oxidation, protein synthesis and degradation and hepatic gluconeogenesis...
August 13, 2018: Nature Reviews. Molecular Cell Biology
Carolina Malagelada, Teodora Pribic, Barbara Ciccantelli, Nicolau Cañellas, Josep Gomez, Nuria Amigo, Anna Accarino, Xavier Correig, Fernando Azpiroz
BACKGROUND: Ingestion of a meal up to maximal tolerance induces unpleasant fullness sensation and changes in circulating metabolites. Our aim was to evaluate the relation between postprandial sensations and the metabolomic responses to a comfort meal. METHODS: In 32 non-obese healthy men, homeostatic sensations (hunger/satiety, fullness), hedonic sensations (digestive well-being, mood), and the metabolomic profile in plasma (low-molecular weight metabolites and lipoprotein profiles) were measured before and 20 minutes after a comfort meal (warm ham and cheese sandwich and juice; total 300 mL; 425 kcal)...
August 13, 2018: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
Da Jung Kim, Seonghae Yoon, Sang Chun Ji, Jinho Yang, Yoon-Keun Kim, SeungHwan Lee, Kyung-Sang Yu, In-Jin Jang, Jae-Yong Chung, Joo-Youn Cho
Ursodeoxycholic acid (UDCA) is a metabolic by-product of intestinal bacteria, showing hepatoprotective effects. However, its underlying molecular mechanisms remain unclear. The purpose of this study was to elucidate the action mechanisms underlying the protective effects of UDCA and vitamin E against liver dysfunction using metabolomics and metagenomic analysis. In this study, we analysed blood and urine samples from patients with obesity and liver dysfunction. Nine patients were randomly assigned to receive UDCA (300 mg twice daily), and 10 subjects received vitamin E (400 IU twice daily) for 8 weeks...
August 8, 2018: Scientific Reports
Catalina A Pomar, Ondrej Kuda, Jan Kopecky, Martina Rombaldova, Heriberto Castro, Catalina Picó, Juana Sánchez, Andreu Palou
Plasma profiles of acylcarnitines (ACs) and amino acids (AAs) may have interest as potential biomarkers. Here we analyzed plasma AC and AA profiles in 2 rat models with different metabolic programming outcomes: offspring of dams fed a cafeteria diet during lactation (O-CAF, with a thin-outside-fat-inside phenotype) and the offspring of dams with diet-induced obesity subjected to dietary normalization before gestation (O-PCaf, nonaltered phenotype). The purpose was to identify early variables that might indicate a propensity for a dysmetabolic state...
August 6, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Susana Conde, Xiaoguang Xu, Hui Guo, Markus Perola, Teresa Fazia, Luisa Bernardinelli, Carlo Berzuini
BACKGROUND: Recent advances in data analysis methods based on principles of Mendelian Randomisation, such as Egger regression and the weighted median estimator, add to the researcher's ability to infer cause-effect links from observational data. Now is the time to gauge the potential of these methods within specific areas of biomedical research. In this paper, we choose a study in metabolomics as an illustrative testbed. We apply Mendelian Randomisation methods in the analysis of data from the DILGOM (Dietary, Lifestyle and Genetic determinants of Obesity and Metabolic syndrome) study, in the context of an effort to identify molecular pathways of cardiovascular disease...
July 9, 2018: BMC Bioinformatics
Rennan Feng, Guozhang Sun, Yunbo Zhang, Qintong Sun, Liyan Ju, Changhao Sun, Cheng Wang
BACKGROUND: The prevalence of obesity is increasing rapidly worldwide, and dietary intake is strongly associated with obesity-related chronic diseases. However, key metabolic perturbations in obese young men with hyperlipemia after high-fat diet (HFD)intervention are not yet clear, and remain to be determined. The aim of this study was to investigate the effects of a short term HFD on glycolipid metabolism, insulin resistance (IR), and urinary metabolomic profiling in young obese male with hyperlipemia...
July 29, 2018: Journal of Diabetes
Liene Bervoets, Guy Massa, Wanda Guedens, Gunter Reekmans, Jean-Paul Noben, Peter Adriaensens
Aim: To identify the plasma metabolic profile associated with childhood obesity and its metabolic phenotypes. Materials & methods: The plasma metabolic profile of 65 obese and 37 normal-weight children was obtained using proton NMR spectroscopy. NMR spectra were rationally divided into 110 integration regions, which reflect relative metabolite concentrations, and were used as statistical variables. Results: Obese children show increased levels of lipids, N-acetyl glycoproteins, and lactate, and decreased levels of several amino acids, α-ketoglutarate, glucose, citrate, and cholinated phospholipids as compared with normal-weight children...
July 2018: Future Science OA
Cláudia Marques, Iva Fernandes, Manuela Meireles, Ana Faria, Jeremy P E Spencer, Nuno Mateus, Conceição Calhau
High-fat (HF) diets are thought to disrupt the profile of the gut microbiota in a manner that may contribute to the neuroinflammation and neurobehavioral changes observed in obesity. Accordingly, we hypothesize that by preventing HF-diet induced dysbiosis it is possible to prevent neuroinflammation and the consequent neurological disorders. Anthocyanins are flavonoids found in berries that exhibit anti-neuroinflammatory properties in the context of obesity. Here, we demonstrate that the blackberry anthocyanin-rich extract (BE) can modulate gut microbiota composition and counteract some of the features of HF-diet induced dysbiosis...
July 27, 2018: Scientific Reports
Angie S Xiang, Peter J Meikle, Andrew L Carey, Bronwyn A Kingwell
Development of therapeutic agents directed towards increasing brown adipose tissue (BAT) energy expenditure to combat obesity and its comorbidities is currently an area of intense research. Both preclinical and clinical studies have suggested a potentially significant role for BAT in regulating whole body energy expenditure as well as glucose and lipid metabolism. Lipids, particularly long chain fatty acids (LCFAs), are recognized as integral substrates in mediating the primary heat-producing functions of BAT, and to date thought to be principally sourced from stored intracellular lipid droplets...
July 24, 2018: Pharmacology & Therapeutics
Evanna L Mills, Kerry A Pierce, Mark P Jedrychowski, Ryan Garrity, Sally Winther, Sara Vidoni, Takeshi Yoneshiro, Jessica B Spinelli, Gina Z Lu, Lawrence Kazak, Alexander S Banks, Marcia C Haigis, Shingo Kajimura, Michael P Murphy, Steven P Gygi, Clary B Clish, Edward T Chouchani
Thermogenesis by brown and beige adipose tissue, which requires activation by external stimuli, can counter metabolic disease1 . Thermogenic respiration is initiated by adipocyte lipolysis through cyclic AMP-protein kinase A signalling; this pathway has been subject to longstanding clinical investigation2-4 . Here we apply a comparative metabolomics approach and identify an independent metabolic pathway that controls acute activation of adipose tissue thermogenesis in vivo. We show that substantial and selective accumulation of the tricarboxylic acid cycle intermediate succinate is a metabolic signature of adipose tissue thermogenesis upon activation by exposure to cold...
August 2018: Nature
Brian D Piccolo, James L Graham, Kimber L Stanhope, Intawat Nookaew, Kelly E Mercer, Sree V Chintapalli, Umesh D Wankhade, Kartik Shankar, Peter J Havel, Sean H Adams
The composition of the gut microbiome is altered in obesity and type 2 diabetes; however, it is not known whether these alterations are mediated by dietary factors or related to declines in metabolic health. To address this, cecal contents were collected from age-matched, chow-fed male UCD-T2DM rats before the onset of diabetes (pre-diabetic PD, n=15); 2 wk recently-diabetic (RD, n=10); 3 mo (D3M, n=11); and 6 mo (D6M, n=8) post-onset of diabetes. Bacterial species and functional gene counts were assessed by shotgun metagenomic sequencing of bacterial DNA in cecal contents, while metabolites were identified by GC-QTOF-MS...
July 17, 2018: American Journal of Physiology. Endocrinology and Metabolism
Anitha Pitchika, Manja Jolink, Christiane Winkler, Sandra Hummel, Nadine Hummel, Jan Krumsiek, Gabi Kastenmüller, Jennifer Raab, Olga Kordonouri, Anette-Gabriele Ziegler, Andreas Beyerlein
AIMS/HYPOTHESIS: Exposure to an intrauterine hyperglycaemic environment has been suggested to increase the offspring's later risk for being overweight or having metabolic abnormalities, but conclusive evidence for pregnancies affected by maternal type 1 diabetes is still lacking. This study aims to analyse the relationship between maternal type 1 diabetes and the offspring's metabolic health and investigate whether birthweight and/or changes in the offspring's metabolome are in the potential pathway...
July 14, 2018: Diabetologia
Martina Palomino-Schätzlein, Rafael Simó, Cristina Hernández, Andreea Ciudin, Pablo Mateos-Gregorio, Antonio Hernández-Mijares, Antonio Pineda-Lucena, José Raúl Herance
The present study was aimed at determining the metabolic profile of PMNs in obese subjects, and to explore its potential relationship with insulin resistance (IR). To achieve this goal, a pilot clinical study was performed using PMNs from 17 patients with obesity and IR, and 17 lean controls without IR, which was validated in an additional smaller cohort (consisting of 10 patients and 10 controls). PMNs were isolated from peripheral blood and nuclear magnetic resonance was used to perform the metabolomic analysis...
2018: PloS One
Samantha L Lewis, Heather M Holl, Maureen T Long, Martha F Mallicote, Samantha A Brooks
Equine metabolic syndrome (EMS), like human metabolic syndrome, comprises a collection of clinical signs related to obesity, insulin dysregulation and susceptibility to secondary inflammatory disease. Although the secondary conditions resulting from EMS can be life-threatening, diagnosis is not straightforward and often complicated by the presence of other concurrent conditions like pituitary pars intermedia dysfunction (PPID). In order to better characterize EMS, we sought to describe the variation within, and correlations between, typical physical and endocrine parameters for EMS...
2018: PloS One
Mengyang Xu, Fanyi Zhong, Richard S Bruno, Kevin D Ballard, Jing Zhang, Jiangjiang Zhu
Although higher intakes of dairy milk are associated with a lower risk of metabolic syndrome (MetS), the underlying protective mechanism remains unclear. This study investigated the dynamic metabolic profile shift following the ingestion of low-fat milk or an isocaloric volume of rice milk in obese individuals with metabolic syndrome (MetS). In a randomized, double-blind, crossover study, postprandial plasma samples ( n = 266) were collected from 19 MetS participants. Plasma samples were analyzed by a targeted metabolomics platform which specifically detects 117 metabolites from 25 metabolic pathways...
July 17, 2018: Journal of Proteome Research
M Armbruster, M Rist, S Seifert, L Frommherz, C Weinert, C Mack, A Roth, B Merz, D Bunzel, R Krüger, S Kulling, B Watzl, A Bub
PURPOSE: Differences in resting energy expenditure (REE) between men and women mainly result from sex-related differences in lean body mass (LBM). So far, a little is known about whether REE and LBM are reflected by a distinct human metabolite profile. Therefore, we aimed to identify plasma and urine metabolite patterns that are associated with REE and LBM of healthy subjects. METHODS: We investigated 301 healthy male and female subjects (18-80 years) under standardized conditions in the cross-sectional KarMeN (Karlsruhe Metabolomics and Nutrition) study...
July 4, 2018: European Journal of Nutrition
Hyekyung Yang, Dong Ho Suh, Dae Hee Kim, Eun Sung Jung, Kwang-Hyeon Liu, Choong Hwan Lee, Cheol-Young Park
BACKGROUND AND PURPOSE: Thiazolidinediones, acting as PPAR-γ ligands, reduce hepatic steatosis in humans and animals. However, the underlying mechanism of this action remains unclear. The purpose of this study was to investigate changes in hepatic metabolites and lipids in response to treatment with the thiazolidinedione pioglitazone in an animal model of obese Type 2 diabetes. EXPERIMENTAL APPROACH: Male Otsuka Long-Evans Tokushima Fatty (OLETF) rats were orally administered either vehicle (control) or pioglitazone (30 mg·kg-1 ) and fed a high-fat diet (60% kcal fat) for 12 weeks...
July 2, 2018: British Journal of Pharmacology
Kuan-Hsing Chen, Yi-Ling Chen, Hsiang-Yu Tang, Cheng-Chieh Hung, Tzung-Hai Yen, Mei-Ling Cheng, Ming-Shi Shiao, Jan-Kan Chen
Dietary leucine supplementation has been explored for the therapeutic intervention of obesity and obesity-induced metabolic dysfunctions. In this study, we aim to examine the effects of dietary leucine supplementation in db/db mice. Mice were treated with or without leucine (1.5% w / v ) in drinking water for 12 weeks. The leucine supplement was found to reduce insulin resistance and hepatic steatosis in db/db mice. Using Nuclear Magnetic Resonance (NMR)-based lipidomics, we found that the reduction of hepatic triglyceride synthesis was correlated with attenuated development of fatty liver...
June 30, 2018: International Journal of Molecular Sciences
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