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Metabolic modeling

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https://www.readbyqxmd.com/read/28941364/nonalcoholic-fatty-liver-disease-incidence-and-impact-on-metabolic-burden-and-death-a-20-year-community-study
#1
Alina M Allen, Therneau M Terry, Joseph J Larson, Alexandra Coward, Virend K Somers, Patrick S Kamath
Recent population-based data on nonalcoholic fatty liver disease (NAFLD) epidemiology in general and incidence in particular, are lacking. We examined trends in NAFLD incidence in a US community, and the impact of NAFLD on incident metabolic comorbidities (MC), cardiovascular (CV) events and mortality. A community cohort of all adults diagnosed with NAFLD in Olmsted County, MN between 1997-2014 was constructed using the Rochester Epidemiology Project database. The yearly incidence rate was calculated. The impact of NAFLD on incident MC, CV events and mortality was studied using a multi-state model, with a 4:1 age and sex-matched general population as reference...
September 23, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28938790/factors-affecting-adipose-tissue-development-in-chickens-a-review
#2
Guoqing Wang, Woo Kyun Kim, Mark A Cline, Elizabeth R Gilbert
The intense genetic selection for rapid growth in broilers has resulted in an increase in voluntary feed intake and growth rate, accompanied by increased fat deposition in adipose tissue depots throughout the body. Adipose tissue expansion is a result of the formation of adipocytes (several processes collectively referred to as adipogenesis) and cellular accumulation of triacylglycerols inside lipid droplets. In mammals, different anatomical depots are metabolically distinct. The molecular and cellular mechanisms underlying adipose tissue development have been characterized in mammalian models, whereas information in avian species is scarce...
October 1, 2017: Poultry Science
https://www.readbyqxmd.com/read/28938734/hyperspectral-microscopy-can-detect-metabolic-heterogeneity-within-bovine-post-compaction-embryos-incubated-under-two-oxygen-concentrations-7-versus-20
#3
Melanie L Sutton-McDowall, Martin Gosnell, Ayad G Anwer, Melissa White, Malcolm Purdey, Andrew D Abell, Ewa M Goldys, Jeremy G Thompson
STUDY QUESTION: Can we separate embryos cultured under either 7% or 20% oxygen atmospheres by measuring their metabolic heterogeneity? SUMMARY ANSWER: Metabolic heterogeneity and changes in metabolic profiles in morula exposed to two different oxygen concentrations were not detectable using traditional fluorophore and two-channel autofluorescence but were detectable using hyperspectral microscopy. WHAT IS KNOWN ALREADY: Increased genetic and morphological blastomere heterogeneity is associated with compromised developmental competence of embryos and currently forms the basis for embryo scoring within the clinic...
October 1, 2017: Human Reproduction
https://www.readbyqxmd.com/read/28938614/phenformin-enhances-the-therapeutic-effect-of-selumetinib-in-kras-mutant-non-small-cell-lung-cancer-irrespective-of-lkb1-status
#4
Jun Zhang, Sreenivas Nannapaneni, Dongsheng Wang, Fakeng Liu, Xu Wang, Rui Jin, Xiuju Liu, Mohammad Aminur Rahman, Xianghong Peng, Guoqing Qian, Zhuo G Chen, Kwok-Kin Wong, Fadlo R Khuri, Wei Zhou, Dong M Shin
MEK inhibition is potentially valuable in targeting KRAS-mutant non-small cell lung cancer (NSCLC). Here, we analyzed whether concomitant LKB1 mutation alters sensitivity to the MEK inhibitor selumetinib, and whether the metabolism drug phenformin can enhance the therapeutic effect of selumetinib in isogenic cell lines with different LKB1 status. Isogenic pairs of KRAS-mutant NSCLC cell lines A549, H460 and H157, each with wild-type and null LKB1, as well as genetically engineered mouse-derived cell lines 634 (kras(G12D/wt)/p53(-/-)/lkb1(wt/wt)) and t2 (kras(G12D/wt)/p53(-/-)/lkb1(-/-)) were used in vitro to analyze the activities of selumetinib, phenformin and their combination...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938479/pulmonary-function-and-sleep-breathing-two-new-targets-for-type-2-diabetes-care
#5
Albert Lecube, Rafael Simó, Maria Pallayova, Naresh M Punjabi, Carolina López-Cano, Cecilia Turino, Cristina Hernández, Ferran Barbé
Population based studies showing the negative impact of type 2 diabetes (T2D) on lung function are overviewed. Among the well-recognized pathophysiological mechanisms, the metabolic pathways related to insulin resistance, low-grade chronic inflammation, leptin resistance, microvascular damage, and autonomic neuropathy are emphasized. Histopathological changes are exposed, and findings reported from experimental models are clearly differentiated from those described in humans. The accelerated decline in pulmonary function that appears in patients with cystic fibrosis with related abnormalities of glucose tolerance and diabetes is considered as an example to further investigate the relationship between T2D and the lung...
September 4, 2017: Endocrine Reviews
https://www.readbyqxmd.com/read/28938471/low-vitamin-b12-in-pregnancy-is-associated-with-adipose-derived-circulating-mirs-targeting-ppar%C3%AE-and-insulin-resistance
#6
Antonysunil Adaikalakoteswari, Manu Vatish, Mohammad Tauqeer Alam, Sascha Ott, Sudhesh Kumar, Ponnusamy Saravanan
Context: Low vitamin B12 (B12) during pregnancy is associated with higher maternal obesity, insulin resistance(IR) and gestational diabetes(GDM). B12 is a key co-factor in 1-carbon metabolism. Objective: We hypothesize that B12 plays a role in epigenetic regulation by altering circulating miRNAs(miRs) during adipocyte differentiation and results in an adverse metabolic phenotype. Design, settings and main-outcome measure: Human pre-adipocyte cell-line(Chub-S7) were differentiated in various B12 concentrations: Control(500nM), LowB12(0...
September 5, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28938461/adipokines-and-their-receptor-are-widely-expressed-and-distinctly-regulated-by-the-metabolic-environment-in-the-prostate-of-male-mice-direct-role-under-normal-and-tumoral-conditions
#7
André Sarmento-Cabral, Fernando L-López, Raúl M Luque
Adipose tissue-derived adipokines (i.e. leptin/adiponectin/resistin) play important roles in the regulation of several pathophysiological processes through the activation of specific receptors. However, although adipokines and their receptors are widely distributed in many tissues and exhibit a clear modulation by the particular metabolic conditions (e.g. obesity and/or fasting), their expression, regulation, and putative action on normal prostate-glands (PGs; a hormone-dependent organ tightly regulated by the endocrine-metabolic milieu) is still to be defined...
August 9, 2017: Endocrinology
https://www.readbyqxmd.com/read/28938459/selective-glucocorticoid-receptor-antagonist-cort125281-activates-brown-adipose-tissue-and-alters-lipid-distribution-in-male-mice
#8
Jan Kroon, Lisa L Koorneef, Jose K van den Heuvel, Cristy R C Verzijl, Nienke M van de Velde, Isabel M Mol, Hetty C M Sips, Hazel Hunt, Patrick C N Rensen, Onno C Meijer
Glucocorticoids influence a wide range of metabolic processes in the human body and excessive glucocorticoid exposure is known to contribute to the development of metabolic disease. We evaluated the utility of the novel glucocorticoid receptor (GR) antagonist CORT125281 for its potential to overcome adiposity, glucose intolerance and dyslipidaemia, and compared this head-to-head with classic GR antagonist RU486 (mifepristone). We show that, while RU486 displays cross-reactivity to the progesterone and androgen receptor, CORT125281 selectively inhibits GR transcriptional activity...
September 18, 2017: Endocrinology
https://www.readbyqxmd.com/read/28938424/adiponectin-predicts-hdl-cholesterol-efflux-capacity-in-adults-irrespective-of-body-mass-index-and-fat-distribution
#9
Gunther Marsche, Sieglinde Zelzer, Andreas Meinitzer, Sabine Kern, Sabine Meissl, Gudrun Pregartner, Daniel Weghuber, Gunter Almer, Harald Mangge
Context: Obesity is associated with hypoadiponectemia, dyslipidemia and increased risk of coronary vascular disease (CVD). Mechanisms linking these conditions remain to be fully understood. Cholesterol efflux capacity (CEC) is a crucial functional property of high-density lipoprotein (HDL) that strongly predicts CVD incidence. Objective: To investigate whether age, fat distribution, and other obesity related factors affect CEC in juvenile and adult overweight/obese participants of the STYJOBS/EDECTA cohort (NCT00482924)...
August 29, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28938248/a-youth-compendium-of-physical-activities-activity-codes-and-metabolic-intensities
#10
Nancy F Butte, Kathleen B Watson, Kate Ridley, Issa F Zakeri, Robert G McMurray, Karin A Pfeiffer, Scott E Crouter, Stephen D Herrmann, David R Bassett, Alexander Long, Zekarias Berhane, Stewart G Trost, Barbara E Ainsworth, David Berrigan, Janet E Fulton
PURPOSE: A Youth Compendium of Physical Activities (Youth Compendium) was developed to estimate the energy costs of physical activities using data on youth only. METHODS: Based on a literature search and pooled data of energy expenditure measurements in youth, the energy costs of 196 activities were compiled in 16 activity categories to form a Youth Compendium of Physical Activities. To estimate the intensity of each activity, measured oxygen consumption (V[Combining Dot Above]O2) was divided by basal metabolic rate (Schofield age-, sex- and mass-specific equations) to produce a youth MET (METy)...
September 21, 2017: Medicine and Science in Sports and Exercise
https://www.readbyqxmd.com/read/28938091/targeting-metabolism-for-cancer-therapy
#11
REVIEW
Alba Luengo, Dan Y Gui, Matthew G Vander Heiden
Metabolic reprogramming contributes to tumor development and introduces metabolic liabilities that can be exploited to treat cancer. Chemotherapies targeting metabolism have been effective cancer treatments for decades, and the success of these therapies demonstrates that a therapeutic window exists to target malignant metabolism. New insights into the differential metabolic dependencies of tumors have provided novel therapeutic strategies to exploit altered metabolism, some of which are being evaluated in preclinical models or clinical trials...
September 21, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28938018/genome-wide-identification-of-bacterial-plant-colonization-genes
#12
Benjamin J Cole, Meghan E Feltcher, Robert J Waters, Kelly M Wetmore, Tatiana S Mucyn, Elizabeth M Ryan, Gaoyan Wang, Sabah Ul-Hasan, Meredith McDonald, Yasuo Yoshikuni, Rex R Malmstrom, Adam M Deutschbauer, Jeffery L Dangl, Axel Visel
Diverse soil-resident bacteria can contribute to plant growth and health, but the molecular mechanisms enabling them to effectively colonize their plant hosts remain poorly understood. We used randomly barcoded transposon mutagenesis sequencing (RB-TnSeq) in Pseudomonas simiae, a model root-colonizing bacterium, to establish a genome-wide map of bacterial genes required for colonization of the Arabidopsis thaliana root system. We identified 115 genes (2% of all P. simiae genes) with functions that are required for maximal competitive colonization of the root system...
September 22, 2017: PLoS Biology
https://www.readbyqxmd.com/read/28937873/effect-of-parathyroidectomy-on-osteopontin-and-undercarboxylated-osteocalcin-in-patients-with-primary-hyperparathyroidism
#13
Raelene E Maser, M James Lenhard, Ryan T Pohlig, P Babu Balagopal, Raafat Abdel-Misih
PURPOSE: Surgical treatment for primary hyperparathyroidism (PHPT) improves bone metabolism. Osteocalcin (OC) and its undercarboxylated form (ucOC) are associated with bone and energy metabolism. Osteopontin (OPN), a multifunctional protein expressed in bone, is involved in resorption, along with β-carboxyl-terminal cross-linking telopeptide of type 1 collagen (β-CTX), and osteoprotegerin (OPG). Our aim was to investigate these biomarkers of bone metabolism in patients with PHPT. METHODS: We examined 30 individuals with PHPT, in a clinical research facility, before and 1 month following parathyroidectomy...
September 22, 2017: Endocrine Research
https://www.readbyqxmd.com/read/28937827/effect-of-saffron-on-metabolic-profile-and-retina-in-apolipoprotein-e-knockout-mice-fed-a-high-fat-diet
#14
Evangelos K Doumouchtsis, Aspasia Tzani, Ilias P Doulamis, Panagiotis Konstantopoulos, Korou Laskarina-Maria, Georgios Agrogiannis, Emmanouil Agapitos, Marilita M Moschos, Alkiviadis Kostakis, Despina N Perrea
Saffron is a spice that has been traditionally used as a regimen for a variety of diseases due to its potent antioxidant attributes. It is well documented that impaired systemic oxidative status is firmly associated with diverse adverse effects including retinal damage. The aim of this study was to investigate the role of saffron administration against the retinal damage in apoE -/- mice fed a high-fat diet, since they constitute a designated experimental model susceptible to oxidative stress. Twenty-one mice were allocated into three groups: Group A (control, n = 7 c57bl/6 mice) received standard chow diet; Group B (high-fat, n = 7 apoE -/- mice) received a high-fat diet; and Group C (high-fat and saffron, n = 7 apoE -/- mice) received a high-fat diet and saffron (25 mg/kg/d) through their drinking water...
September 22, 2017: Journal of Dietary Supplements
https://www.readbyqxmd.com/read/28937622/specificities-of-human-hepatocellular-carcinoma-developed-on-non-alcoholic-fatty-liver-disease-in-absence-of-cirrhosis-revealed-by-tissue-extracts-%C3%A2-h-nmr-spectroscopy
#15
Camille Teilhet, Daniel Morvan, Juliette Joubert-Zakeyh, Anne-Sophie Biesse, Bruno Pereira, Sylvie Massoulier, Pierre Dechelotte, Denis Pezet, Emmanuel Buc, Géraldine Lamblin, Michel Peoc'h, Jack Porcheron, Marie-Paule Vasson, Armando Abergel, Aicha Demidem
There is a rising incidence of non-alcoholic fatty liver disease (NAFLD) as well as of the frequency of Hepato-Cellular Carcinoma (HCC) associated with NAFLD. To seek for putative metabolic pathways specific of the NAFLD etiology, we performed comparative metabolomics between HCC associated with NAFLD and HCC associated with cirrhosis. The study included 28 pairs of HCC tissue versus distant Non-Tumoral Tissue (NTT) collected from patients undergoing hepatectomy. HCC was associated with cirrhosis (n = 9), normal liver (n = 6) and NAFLD (n = 13)...
September 22, 2017: Metabolites
https://www.readbyqxmd.com/read/28937442/orally-active-epoxyeicosatrienoic-acid-analogs
#16
William B Campbell, John D Imig, James M Schmitz, John R Falck
Biologically active epoxyeicosatrienoic acid (EET) regioisomers are synthesized from arachidonic acid by cytochrome P450 epoxygenases of endothelial, myocardial, and renal tubular cells. EETs relax vascular smooth muscle and decrease inflammatory cell adhesion and cytokine release. Renal EETs promote sodium excretion and vasodilation to decrease hypertension. Cardiac EETs reduce infarct size after ischemia-reperfusion injury and decrease fibrosis and inflammation in heart failure. In diabetes, EETs improve insulin sensitivity, increase glucose tolerance, and reduce the renal injury...
September 19, 2017: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/28936849/-effect-of-flavonoids-from-abelmoschus-manihot-on-proliferation-differentiation-of-3t3-l1-preadipocyte-and-insulin-resistance
#17
Hong-Die Cai, Shu-Lan Su, Sheng Guo, Yue Zhu, Da-Wei Qian, Wei-Wei Tao, Jin-Ao Duan
Abelmoschus manihot was rich in flavonoids, which has been reported the activity on protecting angiocarpy and improving renal function. This study aimed to explore the action mechanism of five flavonoids from A. manihot on how to ameliorating insulin resistance through the regulation of the glucose and expression of PPARγ, C/EBPα, SREBP-1, resistin, visfatin, adiponectin in 3T3-L1 adipocytes. After the 3T3-L1 preadipocytes were differentiated into mature adipocytes, insulin resistance model was built. Insulin resistance adipocytes were treated with 5, 100 μmol•L⁻¹ quercetin, isoquercitrin, hyperoside, quercitrin-3'-O-glucoside, gossypetin-8-O-β-glucoside...
December 2016: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
https://www.readbyqxmd.com/read/28936835/-progress-on-studies-of-impact-on-cyp450-enzymes-activity-of-traditional-chinese-medicine-by-cocktail-probe-substrates-approach
#18
REVIEW
Xi Du, Xin He, Yu-Hong Huang, Zi-Qiang Li
Cocktail probe substrates approach is a fast, sensitive and high through put method to determine cytochrome P450 enzymes activity. It has been widely used to screen early drug development, analyze drug metabolism types and confirm the metabolism pathways, study drug-drug interactions, optimize clinical regimen, evaluate post marketing drugs and help liver/kidney pathological studies. This article reviewed characteristics of Cocktail probe substrates, focused on the application to traditional Chinese medicine to CYP450 system as follows: the metabolic pathway research of Chinese herb active ingredients; processing way and compatibility of medical herbs affect CYP450; find out the metabolic characteristic of Chinese patent medicine, study in pharmacy of national minority; do research in liver protective effect of traditional Chinese medicine and evaluate traditional Chinese medicine syndromes in animal models...
December 2016: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
https://www.readbyqxmd.com/read/28936800/evodiamine-ameliorates-liver-fibrosis-in-rats-via-tgf-%C3%AE-1-smad-signaling-pathway
#19
Dongmei Yang, Li Li, Shanjun Qian, Lixin Liu
Liver fibrosis is considered to be a result of chronic liver pathological changes, and hepatic stellate cells (HSCs) play an important role during this process. Evodiamine, an indole alkaloid derived from Evodia rutaecarpa, exhibits pharmacological activities. This study focused on the effects of evodiamine on carbon tetrachloride (CCl4)-induced liver fibrosis in rats and HSCs in vitro via the TGF-β1/Smad signaling pathway. A liver fibrosis rat model was established by the intraperitoneal injection of CCl4 (3 ml/kg, 30% in olive oil)...
September 21, 2017: Journal of Natural Medicines
https://www.readbyqxmd.com/read/28936623/acute-renal-metabolic-effect-of-metformin-assessed-with-hyperpolarised-mri-in-rats
#20
Haiyun Qi, Per M Nielsen, Marie Schroeder, Lotte B Bertelsen, Fredrik Palm, Christoffer Laustsen
AIMS/HYPOTHESIS: Metformin inhibits hepatic mitochondrial glycerol phosphate dehydrogenase, thereby increasing cytosolic lactate and suppressing gluconeogenesis flux in the liver. This inhibition alters cytosolic and mitochondrial reduction-oxidation (redox) potential, which has been reported to protect organ function in several disease states including diabetes. In this study, we investigated the acute metabolic and functional changes induced by metformin in the kidneys of both healthy and insulinopenic Wistar rats used as a model of diabetes...
September 21, 2017: Diabetologia
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