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Molecular Metabolism

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https://www.readbyqxmd.com/read/27900263/islet-chrebp-%C3%AE-is-increased-in-diabetes-and-controls-chrebp-%C3%AE-and-glucose-induced-gene-expression-via-a-negative-feedback-loop
#1
Gu Jing, Junqin Chen, Guanlan Xu, Anath Shalev
OBJECTIVE: Carbohydrate-response element-binding protein (ChREBP) is the major transcription factor conferring glucose-induced gene expression in pancreatic islets, liver and adipose tissue. Recently, a novel ChREBP isoform, ChREBP-β, was identified in adipose tissue and found to be also expressed in islets and involved in glucose-induced beta cell proliferation. However, the physiological function of this less abundant β-isoform in the islet, and in diabetes, is largely unknown. The aims of the present study, therefore, were to determine how diabetes affects ChREBP-β and elucidate its physiological role in pancreatic beta cells...
December 2016: Molecular Metabolism
https://www.readbyqxmd.com/read/27900262/impaired-histone-deacetylases-5-and-6-expression-mimics-the-effects-of-obesity-and-hypoxia-on-adipocyte-function
#2
Julien Bricambert, Dimitri Favre, Saška Brajkovic, Amélie Bonnefond, Raphael Boutry, Roberto Salvi, Valérie Plaisance, Mohamed Chikri, Giulia Chinetti-Gbaguidi, Bart Staels, Vittorio Giusti, Robert Caiazzo, François Pattou, Gérard Waeber, Philippe Froguel, Amar Abderrahmani
OBJECTIVE: The goal of the study was to investigate the role of histone deacetylases (HDACs) in adipocyte function associated with obesity and hypoxia. METHODS: Total proteins and RNA were prepared from human visceral adipose tissues (VAT) of human obese and normal weight subjects and from white adipose tissue (WAT) of C57Bl6-Rj mice fed a normal or high fat diet (HFD) for 16 weeks. HDAC activity was measured by colorimetric assay whereas the gene and protein expression were monitored by real-time PCR and by western blotting, respectively...
December 2016: Molecular Metabolism
https://www.readbyqxmd.com/read/27900261/targeting-the-endocannabinoid-cb1-receptor-system-for-treating-obesity-in-prader-willi-syndrome
#3
Ibrahim Knani, Brian J Earley, Shiran Udi, Alina Nemirovski, Rivka Hadar, Asaad Gammal, Resat Cinar, Harry J Hirsch, Yehuda Pollak, Itai Gross, Talia Eldar-Geva, Daniela P Reyes-Capo, Joan C Han, Andrea M Haqq, Varda Gross-Tsur, Rachel Wevrick, Joseph Tam
OBJECTIVE: Extreme obesity is a core phenotypic feature of Prader-Willi syndrome (PWS). Among numerous metabolic regulators, the endocannabinoid (eCB) system is critically involved in controlling feeding, body weight, and energy metabolism, and a globally acting cannabinoid-1 receptor (CB1R) blockade reverses obesity both in animals and humans. The first-in-class CB1R antagonist rimonabant proved effective in inducing weight loss in adults with PWS. However, it is no longer available for clinical use because of its centrally mediated, neuropsychiatric, adverse effects...
December 2016: Molecular Metabolism
https://www.readbyqxmd.com/read/27900260/gut-microbiota-and-glucometabolic-alterations-in-response-to-recurrent-partial-sleep-deprivation-in-normal-weight-young-individuals
#4
Christian Benedict, Heike Vogel, Wenke Jonas, Anni Woting, Michael Blaut, Annette Schürmann, Jonathan Cedernaes
OBJECTIVE: Changes to the microbial community in the human gut have been proposed to promote metabolic disturbances that also occur after short periods of sleep loss (including insulin resistance). However, whether sleep loss affects the gut microbiota remains unknown. METHODS: In a randomized within-subject crossover study utilizing a standardized in-lab protocol (with fixed meal times and exercise schedules), we studied nine normal-weight men at two occasions: after two nights of partial sleep deprivation (PSD; sleep opportunity 02:45-07:00 h), and after two nights of normal sleep (NS; sleep opportunity 22:30-07:00 h)...
December 2016: Molecular Metabolism
https://www.readbyqxmd.com/read/27900259/dietary-fat-and-gut-microbiota-interactions-determine-diet-induced-obesity-in-mice
#5
Raphaela Kübeck, Catalina Bonet-Ripoll, Christina Hoffmann, Alesia Walker, Veronika Maria Müller, Valentina Luise Schüppel, Ilias Lagkouvardos, Birgit Scholz, Karl-Heinz Engel, Hannelore Daniel, Philippe Schmitt-Kopplin, Dirk Haller, Thomas Clavel, Martin Klingenspor
OBJECTIVE: Gut microbiota may promote positive energy balance; however, germfree mice can be either resistant or susceptible to diet-induced obesity (DIO) depending on the type of dietary intervention. We here sought to identify the dietary constituents that determine the susceptibility to body fat accretion in germfree (GF) mice. METHODS: GF and specific pathogen free (SPF) male C57BL/6N mice were fed high-fat diets either based on lard or palm oil for 4 wks. Mice were metabolically characterized at the end of the feeding trial...
December 2016: Molecular Metabolism
https://www.readbyqxmd.com/read/27900258/adipocyte-specific-hypoxia-inducible-gene-2-promotes-fat-deposition-and-diet-induced-insulin-resistance
#6
Marina T DiStefano, Rachel J Roth Flach, Ozlem Senol-Cosar, Laura V Danai, Joseph V Virbasius, Sarah M Nicoloro, Juerg Straubhaar, Sezin Dagdeviren, Martin Wabitsch, Olga T Gupta, Jason K Kim, Michael P Czech
OBJECTIVE: Adipose tissue relies on lipid droplet (LD) proteins in its role as a lipid-storing endocrine organ that controls whole body metabolism. Hypoxia-inducible Gene 2 (Hig2) is a recently identified LD-associated protein in hepatocytes that promotes hepatic lipid storage, but its role in the adipocyte had not been investigated. Here we tested the hypothesis that Hig2 localization to LDs in adipocytes promotes adipose tissue lipid deposition and systemic glucose homeostasis. METHOD: White and brown adipocyte-deficient (Hig2(fl/fl) × Adiponection cre+) and selective brown/beige adipocyte-deficient (Hig2(fl/fl) × Ucp1 cre+) mice were generated to investigate the role of Hig2 in adipose depots...
December 2016: Molecular Metabolism
https://www.readbyqxmd.com/read/27900257/does-osteopontin-induce-adipose-tissue-inflammation-by-local-macrophage-proliferation
#7
Florian Kahles, Hannes M Findeisen
No abstract text is available yet for this article.
December 2016: Molecular Metabolism
https://www.readbyqxmd.com/read/27818940/critical-role-for-adenosine-receptor-a2a-in-%C3%AE-cell-proliferation
#8
Nadja Schulz, Ka-Cheuk Liu, Jérémie Charbord, Charlotte L Mattsson, Lingjie Tao, Dominika Tworus, Olov Andersson
OBJECTIVE: Pharmacological activation of adenosine signaling has been shown to increase β-cell proliferation and thereby β-cell regeneration in zebrafish and rodent models of diabetes. However, whether adenosine has an endogenous role in regulating β-cell proliferation is unknown. The objective of this study was to determine whether endogenous adenosine regulates β-cell proliferation-either in the basal state or states of increased demand for insulin-and to delineate the mechanisms involved...
November 2016: Molecular Metabolism
https://www.readbyqxmd.com/read/27818939/osteopontin-is-a-key-player-for-local-adipose-tissue-macrophage-proliferation-in-obesity
#9
Matteo Tardelli, Karina Zeyda, Veronica Moreno-Viedma, Bettina Wanko, Nicole G Grün, Günther Staffler, Maximilian Zeyda, Thomas M Stulnig
OBJECTIVE: Recent findings point towards an important role of local macrophage proliferation also in obesity-induced adipose tissue inflammation that underlies insulin resistance and type 2 diabetes. Osteopontin (OPN) is an inflammatory cytokine highly upregulated in adipose tissue (AT) of obese and has repeatedly been shown to be functionally involved in adipose-tissue inflammation and metabolic sequelae. In the present work, we aimed at unveiling both the role of OPN in human monocyte and macrophage proliferation as well as the impact of OPN deficiency on local macrophage proliferation in a mouse model for diet-induced obesity...
November 2016: Molecular Metabolism
https://www.readbyqxmd.com/read/27818938/modulation-of-ambient-temperature-promotes-inflammation-and-initiates-atherosclerosis-in-wild-type-c57bl-6-mice
#10
Daniel A Giles, Bhama Ramkhelawon, Elizabeth M Donelan, Traci E Stankiewicz, Susan B Hutchison, Rajib Mukherjee, Monica Cappelletti, Rebekah Karns, Christopher L Karp, Kathryn J Moore, Senad Divanovic
OBJECTIVES: Obesity and obesity-associated inflammation is central to a variety of end-organ sequelae including atherosclerosis, a leading cause of death worldwide. Although mouse models have provided important insights into the immunopathogenesis of various diseases, modeling atherosclerosis in mice has proven difficult. Specifically, wild-type (WT) mice are resistant to developing atherosclerosis, while commonly used genetically modified mouse models of atherosclerosis are poor mimics of human disease...
November 2016: Molecular Metabolism
https://www.readbyqxmd.com/read/27818937/depot-specific-differences-in-angiogenic-capacity-of-adipose-tissue-in-differential-susceptibility-to-diet-induced-obesity
#11
Mun-Gyu Song, Hye-Jin Lee, Bo-Yeong Jin, Ruth Gutierrez-Aguilar, Kyung-Ho Shin, Sang-Hyun Choi, Sung Hee Um, Dong-Hoon Kim
OBJECTIVE: Adipose tissue (AT) expansion requires AT remodeling, which depends on AT angiogenesis. Modulation of AT angiogenesis could have therapeutic promise for the treatment of obesity. However, it is unclear how the capacity of angiogenesis in each adipose depot is affected by over-nutrition. Therefore, we investigated the angiogenic capacity (AC) of subcutaneous and visceral fats in lean and obese mice. METHODS: We compared the AC of epididymal fat (EF) and inguinal fat (IF) using an angiogenesis assay in diet-induced obese (DIO) mice and diet-resistant (DR) mice fed a high-fat diet (HFD)...
November 2016: Molecular Metabolism
https://www.readbyqxmd.com/read/27818936/suppressing-hyperinsulinemia-prevents-obesity-but-causes-rapid-onset-of-diabetes-in-leptin-deficient-lep-ob-ob-mice
#12
Anna M D'souza, James D Johnson, Susanne M Clee, Timothy J Kieffer
OBJECTIVE: Hyperinsulinemia is commonly associated with obesity. Mice deficient in the adipose-derived hormone leptin (Lep(ob/ob)) develop hyperinsulinemia prior to onset of obesity and glucose intolerance. Whether the excess of circulating insulin is a major contributor to obesity and impaired glucose homeostasis in Lep(ob/ob) mice is unclear. It has been reported previously that diet-induced obesity in mice can be prevented by reducing insulin gene dosage. In the present study, we examined the effects of genetic insulin reduction in Lep(ob/ob) mice on circulating insulin, body composition, and glucose homeostasis...
November 2016: Molecular Metabolism
https://www.readbyqxmd.com/read/27818935/intestinal-crebh-overexpression-prevents-high-cholesterol-diet-induced-hypercholesterolemia-by-reducing-npc1l1-expression
#13
Takuya Kikuchi, Kana Orihara, Fusaka Oikawa, Song-Iee Han, Motoko Kuba, Kanako Okuda, Aoi Satoh, Yoshinori Osaki, Yoshinori Takeuchi, Yuichi Aita, Takashi Matsuzaka, Hitoshi Iwasaki, Shigeru Yatoh, Motohiro Sekiya, Naoya Yahagi, Hiroaki Suzuki, Hirohito Sone, Yoshimi Nakagawa, Nobuhiro Yamada, Hitoshi Shimano
OBJECTIVE: The transcription factor cyclic AMP-responsive element-binding protein H (CREBH, encoded by Creb3l3) is highly expressed in the liver and small intestine. Hepatic CREBH contributes to glucose and triglyceride metabolism by regulating fibroblast growth factor 21 (Fgf21) expression. However, the intestinal CREBH function remains unknown. METHODS: To investigate the influence of intestinal CREBH on cholesterol metabolism, we compared plasma, bile, fecal, and tissue cholesterol levels between wild-type (WT) mice and mice overexpressing active human CREBH mainly in the small intestine (CREBH Tg mice) under different dietary conditions...
November 2016: Molecular Metabolism
https://www.readbyqxmd.com/read/27818934/glucose-6-phosphate-dehydrogenase-contributes-to-the-regulation-of-glucose-uptake-in-skeletal-muscle
#14
Robert S Lee-Young, Nolan J Hoffman, Kate T Murphy, Darren C Henstridge, Dorit Samocha-Bonet, Andrew L Siebel, Peter Iliades, Borivoj Zivanovic, Yet H Hong, Timothy D Colgan, Michael J Kraakman, Clinton R Bruce, Paul Gregorevic, Glenn K McConell, Gordon S Lynch, Grant R Drummond, Bronwyn A Kingwell, Jerry R Greenfield, Mark A Febbraio
OBJECTIVE: The development of skeletal muscle insulin resistance is an early physiological defect, yet the intracellular mechanisms accounting for this metabolic defect remained unresolved. Here, we have examined the role of glucose-6-phosphate dehydrogenase (G6PDH) activity in the pathogenesis of insulin resistance in skeletal muscle. METHODS: Multiple mouse disease states exhibiting insulin resistance and glucose intolerance, as well as obese humans defined as insulin-sensitive, insulin-resistant, or pre-diabetic, were examined...
November 2016: Molecular Metabolism
https://www.readbyqxmd.com/read/27818933/inhibition-of-citrate-cotransporter-slc13a5-mindy-by-rnai-improves-hepatic-insulin-sensitivity-and-prevents-diet-induced-non-alcoholic-fatty-liver-disease-in-mice
#15
Sebastian Brachs, Angelika F Winkel, Hui Tang, Andreas L Birkenfeld, Bodo Brunner, Kerstin Jahn-Hofmann, Daniel Margerie, Hartmut Ruetten, Dieter Schmoll, Joachim Spranger
OBJECTIVE: Non-alcoholic fatty liver disease is a world-wide health concern and risk factor for cardio-metabolic diseases. Citrate uptake modifies intracellular hepatic energy metabolism and is controlled by the conserved sodium-dicarboxylate cotransporter solute carrier family 13 member 5 (SLC13A5, mammalian homolog of INDY: mINDY). In Drosophila melanogaster and Caenorhabditis elegans INDY reduction decreased whole-body lipid accumulation. Genetic deletion of Slc13a5 in mice protected from diet-induced adiposity and insulin resistance...
November 2016: Molecular Metabolism
https://www.readbyqxmd.com/read/27818932/analysis-of-energy-metabolism-in-humans-a-review-of-methodologies
#16
REVIEW
Yan Y Lam, Eric Ravussin
BACKGROUND: Obesity is a consequence of chronic energy imbalance. We need accurate and precise measurements of energy intake and expenditure, as well as the related behaviors, to fully understand how energy homeostasis is regulated in order to develop interventions and evaluate their effectiveness to combat the global obesity epidemic. SCOPE OF REVIEW: We provide an in-depth review of the methodologies currently used to measure energy intake and expenditure in humans, including their principles, advantages, and limitations in the clinical research setting...
November 2016: Molecular Metabolism
https://www.readbyqxmd.com/read/27689018/the-diabetes-medication-canagliflozin-reduces-cancer-cell-proliferation-by-inhibiting-mitochondrial-complex-i-supported-respiration
#17
Linda A Villani, Brennan K Smith, Katarina Marcinko, Rebecca J Ford, Lindsay A Broadfield, Alex E Green, Vanessa P Houde, Paola Muti, Theodoros Tsakiridis, Gregory R Steinberg
OBJECTIVE: The sodium-glucose transporter 2 (SGLT2) inhibitors Canagliflozin and Dapagliflozin are recently approved medications for type 2 diabetes. Recent studies indicate that SGLT2 inhibitors may inhibit the growth of some cancer cells but the mechanism(s) remain unclear. METHODS: Cellular proliferation and clonogenic survival were used to assess the sensitivity of prostate and lung cancer cell growth to the SGLT2 inhibitors. Oxygen consumption, extracellular acidification rate, cellular ATP, glucose uptake, lipogenesis, and phosphorylation of AMP-activated protein kinase (AMPK), acetyl-CoA carboxylase, and the p70S6 kinase were assessed...
October 2016: Molecular Metabolism
https://www.readbyqxmd.com/read/27689017/osteocalcin-is-necessary-and-sufficient-to-maintain-muscle-mass-in-older-mice
#18
Paula Mera, Kathrin Laue, Jianwen Wei, Julian Meyer Berger, Gerard Karsenty
OBJECTIVE: A decrease in muscle protein turnover and therefore in muscle mass is a hallmark of aging. Because the circulating levels of the bone-derived hormone osteocalcin decline steeply during aging in mice, monkeys and humans we asked here whether this hormone might regulate muscle mass as mice age. METHODS: We examined muscle mass and strength in mice lacking osteocalcin (Ocn-/-) or its receptor in all cells (Gprc6a-/-) or specifically in myofibers (Gprc6a Mck -/-) as well as in 9 month-old WT mice receiving exogenous osteocalcin for 28 days...
October 2016: Molecular Metabolism
https://www.readbyqxmd.com/read/27689016/dynamic-dna-methylation-landscape-defines-brown-and-white-cell-specificity-during-adipogenesis
#19
Yen Ching Lim, Sook Yoong Chia, Shengnan Jin, Weiping Han, Chunming Ding, Lei Sun
OBJECTIVE: DNA methylation may be a stable epigenetic contributor to defining fat cell lineage. METHODS: We performed reduced representation bisulfite sequencing (RRBS) and RNA-seq to depict a genome-wide integrative view of the DNA methylome and transcriptome during brown and white adipogenesis. RESULTS: Our analysis demonstrated that DNA methylation is a stable epigenetic signature for brown and white cell lineage before, during, and after differentiation...
October 2016: Molecular Metabolism
https://www.readbyqxmd.com/read/27689015/sex-differences-in-obesity-development-in-pair-fed-neuronal-lipoprotein-lipase-deficient-mice
#20
Hong Wang, Yongping Wang, Matthew D Taussig, Robert H Eckel
OBJECTIVE: Compared to men, postmenopausal women suffer from a disproportionate burden of many co-morbidities associated with obesity, e.g. cardiovascular disease, cancer, and dementia. The underlying mechanism for this sex difference is not well understood but is believed to relate to absence of the protective effect of estrogen through the action of estrogen receptor alpha (ERα) in the central nervous system. With the recently developed neuron-specific lipoprotein lipase deficient mice (NEXLPL-/-) (Wang et al...
October 2016: Molecular Metabolism
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