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Molecular Metabolism

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https://www.readbyqxmd.com/read/28180064/dipeptidyl-peptidase-4-inhibitor-treatment-induces-a-greater-increase-in-plasma-levels-of-bioactive-gip-than-glp-1-in-non-diabetic-subjects
#1
Tsuyoshi Yanagimachi, Yukihiro Fujita, Yasutaka Takeda, Jun Honjo, Hidemitsu Sakagami, Hiroya Kitsunai, Yumi Takiyama, Atsuko Abiko, Yuichi Makino, Timothy J Kieffer, Masakazu Haneda
OBJECTIVE: Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) possess multiple bioactive isoforms that are rendered non-insulinotropic by the enzyme dipeptidyl peptidase-4 (DPP-4). Recently, some ELISA kits have been developed to specifically measure "active" GIP and GLP-1, but it is unclear if these kits can accurately quantify all bioactive forms. Therefore, it remains uncertain to what extent treatment with a DPP-4 inhibitor boosts levels of biologically active GIP and GLP-1...
February 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28180063/carnitine-acetyltransferase-crat-expression-in-macrophages-is-dispensable-for-nutrient-stress-sensing-and-inflammation
#2
Emily L Goldberg, Vishwa Deep Dixit
OBJECTIVE: Fatty acid oxidation in macrophages is thought to regulate inflammatory status and insulin-sensitivity. An important unanswered question in this field is whether carnitine acetyl-transferase (CrAT) that regulates fatty acid oxidation and mitochondrial acetyl-CoA balance is required to integrate nutrient stress sensing to inflammatory response in macrophages. METHODS: Mice with myeloid lineage-specific Crat deletion were subjected to several metabolic stressors, including high-fat diet-induced obesity, fasting, and LPS-induced endotoxemia...
February 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28180062/blocking-inos-and-endoplasmic-reticulum-stress-synergistically-improves-insulin-resistance-in-mice
#3
Tamires M Zanotto, Paula G F Quaresma, Dioze Guadagnini, Lais Weissmann, Andressa C Santos, Juliana F Vecina, Kelly Calisto, Andrey Santos, Patrícia O Prada, Mario J A Saad
OBJECTIVE: Recent data show that iNOS has an essential role in ER stress in obesity. However, whether iNOS is sufficient to account for obesity-induced ER stress and Unfolded Protein Response (UPR) has not yet been investigated. In the present study, we used iNOS knockout mice to investigate whether high-fat diet (HFD) can still induce residual ER stress-associated insulin resistance. METHODS: For this purpose, we used the intraperitoneal glucose tolerance test (GTT), euglycemic-hyperinsulinemic clamp, western blotting and qPCR in liver, muscle, and adipose tissue of iNOS KO and control mice on HFD...
February 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28180061/kinase-suppressor-of-ras-2-ksr2-expression-in-the-brain-regulates-energy-balance-and-glucose-homeostasis
#4
Lili Guo, Diane L Costanzo-Garvey, Deandra R Smith, Beth K Neilsen, Richard G MacDonald, Robert E Lewis
OBJECTIVE: Kinase Suppressor of Ras 2 (KSR2) is a molecular scaffold coordinating Raf/MEK/ERK signaling that is expressed at high levels in the brain. KSR2 disruption in humans and mice causes obesity and insulin resistance. Understanding the anatomical location and mechanism of KSR2 function should lead to a better understanding of physiological regulation over energy balance. METHODS: Mice bearing floxed alleles of KSR2 (KSR2(fl/fl)) were crossed with mice expressing the Cre recombinase expressed by the Nestin promoter (Nes-Cre) to produce Nes-CreKSR2(fl/fl) mice...
February 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28180060/gprc6a-jack-of-all-metabolism-or-master-of-none
#5
REVIEW
Min Pi, Satoru Kenneth Nishimoto, L Darryl Quarles
BACKGROUND: GPRC6A, a widely expressed G-protein coupled receptor, is proposed to be a master regulator of complex endocrine networks and metabolic processes. GPRC6A is activated by multiple ligands, including osteocalcin (Ocn), testosterone (T), basic amino acids, and various cations. SCOPE OF REVIEW: We review the controversy surrounding GPRC6A functions. In mice, GPRC6A is proposed to integrate metabolic functions through the coordinated secretion of hormones, including insulin, GLP-1, T, and IL-6, and direct effects of this receptor to control glucose and fat metabolism in the liver, skeletal muscle, and fat...
February 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28180059/jnk-at-the-crossroad-of-obesity-insulin-resistance-and-cell-stress-response
#6
REVIEW
Giovanni Solinas, Barbara Becattini
BACKGROUND: The cJun-N-terminal-kinase (JNK) plays a central role in the cell stress response, with outcomes ranging from cell death to cell proliferation and survival, depending on the specific context. JNK is also one of the most investigated signal transducers in obesity and insulin resistance, and studies have identified new molecular mechanisms linking obesity and insulin resistance. Emerging evidence indicates that whereas JNK1 and JNK2 isoforms promote the development of obesity and insulin resistance, JNK3 activity protects from excessive adiposity...
February 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28180058/leptin-deficient-mice-are-not-hypothermic-they-are-anapyrexic
#7
Alexander W Fischer, Barbara Cannon, Jan Nedergaard
No abstract text is available yet for this article.
February 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28123946/endospanin1-affects-oppositely-body-weight-regulation-and-glucose-homeostasis-by-differentially-regulating-central-leptin-signaling
#8
Virginie Vauthier, Clara Roujeau, Patty Chen, Chamsy Sarkis, Stéphanie Migrenne, Toru Hosoi, Koichiro Ozawa, Yves Rouillé, Marc Foretz, Jacques Mallet, Jean-Marie Launay, Christophe Magnan, Ralf Jockers, Julie Dam
: The hypothalamic arcuate nucleus (ARC) is a major integration center for energy and glucose homeostasis that responds to leptin. Resistance to leptin in the ARC is an important component of the development of obesity and type 2 diabetes. Recently, we showed that Endospanin1 (Endo1) is a negative regulator of the leptin receptor (OBR) that interacts with OBR and retains the receptor inside the cell, leading to a decreased activation of the anorectic STAT3 pathway. Endo1 is up-regulated in the ARC of high fat diet (HFD)-fed mice, and its silencing in the ARC of lean and obese mice prevents and reverses the development of obesity...
January 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28123945/the-neuropeptide-tlqp-21-opposes-obesity-via%C3%A2-c3ar1-mediated-enhancement-of-adrenergic-induced-lipolysis
#9
Cheryl Cero, Maria Razzoli, Ruijun Han, Bhavani Shankar Sahu, Jessica Patricelli, ZengKui Guo, Nathan A Zaidman, John M Miles, Scott M O'Grady, Alessandro Bartolomucci
OBJECTIVES: Obesity is characterized by excessive fat mass and is associated with serious diseases such as type 2 diabetes. Targeting excess fat mass by sustained lipolysis has been a major challenge for anti-obesity therapies due to unwanted side effects. TLQP-21, a neuropeptide encoded by the pro-peptide VGF (non-acronymic), that binds the complement 3a receptor 1 (C3aR1) on the adipocyte membrane, is emerging as a novel modulator of adipocyte functions and a potential target for obesity-associated diseases...
January 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28123944/celastrol-ameliorates-liver-metabolic-damage-caused-by-a-high-fat-diet-through-sirt1
#10
Yinliang Zhang, Chao Geng, Xiaoyan Liu, Meixia Li, Mingyue Gao, Xiaojun Liu, Fude Fang, Yongsheng Chang
OBJECTIVE: Celastrol was recently identified as a potential novel treatment for obesity. However, the effect of Celastrol on nonalcoholic fatty liver disease (NAFLD) remains elusive. The aim of this study is to evaluate the role of Celastrol in NAFLD. METHODS: Functional studies were performed using wild-type C57BL/6J (WT) mice and liver specific Sirt1-deficient (LKO) mice. The molecular mechanism was explored in primary mouse liver and primary hepatocytes. RESULTS: When WT mice receiving a high-fat diet (HFD) were treated with Celastrol, reductions in body weight, subcutaneous and visceral fat content, and liver lipid droplet formation were observed, along with reduced hepatic intracellular triglyceride and serum triglyceride, free fatty acid, and ALT concentrations...
January 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28123943/systemic-insulin-sensitivity-is-regulated-by-gps2-inhibition-of-akt-ubiquitination-and-activation-in-adipose-tissue
#11
Carly T Cederquist, Claudia Lentucci, Camila Martinez-Calejman, Vanessa Hayashi, Joseph Orofino, David Guertin, Susan K Fried, Mi-Jeong Lee, M Dafne Cardamone, Valentina Perissi
OBJECTIVE: Insulin signaling plays a unique role in the regulation of energy homeostasis and the impairment of insulin action is associated with altered lipid metabolism, obesity, and Type 2 Diabetes. The main aim of this study was to provide further insight into the regulatory mechanisms governing the insulin signaling pathway by investigating the role of non-proteolytic ubiquitination in insulin-mediated activation of AKT. METHODS: The molecular mechanism of AKT regulation through ubiquitination is first dissected in vitro in 3T3-L1 preadipocytes and then validated in vivo using mice with adipo-specific deletion of GPS2, an endogenous inhibitor of Ubc13 activity (GPS2-AKO mice)...
January 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28123942/fetal-development-of-subcutaneous-white-adipose-tissue-is-dependent-on-zfp423
#12
Mengle Shao, Chelsea Hepler, Lavanya Vishvanath, Karen A MacPherson, Napoleon C Busbuso, Rana K Gupta
OBJECTIVE: Zfp423 is a multi zinc-finger transcription factor expressed in preadipocytes and mature adipocytes in vivo. Our recent work has revealed a critical role for Zfp423 in maintaining the fate of white adipocytes in adult mice through suppression of the beige cell thermogenic gene program; loss of Zfp423 in mature adipocytes of adult mice results in a white-to-beige phenotypic switch. However, the exact requirements of Zfp423 in the fetal stages of early adipose development in vivo have not been clarified...
January 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28123941/conserved-function-of-the-long-noncoding-rna-blnc1-in-brown-adipocyte-differentiation
#13
Lin Mi, Xu-Yun Zhao, Siming Li, Gongshe Yang, Jiandie D Lin
OBJECTIVE: Long noncoding RNAs (lncRNAs) are emerging as important regulators of diverse biological processes. Recent work has demonstrated that the inducible lncRNA Blnc1 stimulates thermogenic gene expression during brown and beige adipocyte differentiation. However, whether Blnc1 is functionally conserved in humans has not been explored. In addition, the molecular basis of the Blnc1 ribonucleoprotein complex in thermogenic gene induction remains incompletely understood. The aims of the current study were to: i) investigate functional conservation of Blnc1 in mice and humans and ii) elucidate the molecular mechanisms by which Blnc1 controls the thermogenic gene program in brown adipocytes...
January 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28123940/genome-wide-dna-promoter-methylation-and-transcriptome-analysis-in-human-adipose-tissue-unravels-novel-candidate-genes-for-obesity
#14
Maria Keller, Lydia Hopp, Xuanshi Liu, Tobias Wohland, Kerstin Rohde, Raffaella Cancello, Matthias Klös, Karl Bacos, Matthias Kern, Fabian Eichelmann, Arne Dietrich, Michael R Schön, Daniel Gärtner, Tobias Lohmann, Miriam Dreßler, Michael Stumvoll, Peter Kovacs, Anna-Maria DiBlasio, Charlotte Ling, Hans Binder, Matthias Blüher, Yvonne Böttcher
OBJECTIVE/METHODS: DNA methylation plays an important role in obesity and related metabolic complications. We examined genome-wide DNA promoter methylation along with mRNA profiles in paired samples of human subcutaneous adipose tissue (SAT) and omental visceral adipose tissue (OVAT) from non-obese vs. obese individuals. RESULTS: We identified negatively correlated methylation and expression of several obesity-associated genes in our discovery dataset and in silico replicated ETV6 in two independent cohorts...
January 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28123939/global-ip6k1-deletion-enhances-temperature-modulated-energy-expenditure-which-reduces-carbohydrate-and-fat-induced-weight-gain
#15
Qingzhang Zhu, Sarbani Ghoshal, Richa Tyagi, Anutosh Chakraborty
OBJECTIVE: IP6 kinases (IP6Ks) regulate cell metabolism and survival. Mice with global (IP6K1-KO) or adipocyte-specific (AdKO) deletion of IP6K1 are protected from diet induced obesity (DIO) at ambient (23 °C) temperature. AdKO mice are lean primarily due to increased AMPK mediated thermogenic energy expenditure (EE). Thus, at thermoneutral (30 °C) temperature, high fat diet (HFD)-fed AdKO mice expend energy and gain body weight, similar to control mice. IP6K1 is ubiquitously expressed; thus, it is critical to determine to what extent the lean phenotype of global IP6K1-KO mice depends on environmental temperature...
January 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28123938/intestinal-invalidation-of-the-glucose-transporter-glut2-delays-tissue-distribution-of-glucose-and-reveals-an-unexpected-role-in-gut-homeostasis
#16
Charlotte C Schmitt, Thomas Aranias, Thomas Viel, Danielle Chateau, Maude Le Gall, Anne-Judith Waligora-Dupriet, Chloé Melchior, Ophélie Rouxel, Nathalie Kapel, Guillaume Gourcerol, Bertrand Tavitian, Agnès Lehuen, Edith Brot-Laroche, Armelle Leturque, Patricia Serradas, Alexandra Grosfeld
OBJECTIVE: Intestinal glucose absorption is orchestrated by specialized glucose transporters such as SGLT1 and GLUT2. However, the role of GLUT2 in the regulation of glucose absorption remains to be fully elucidated. METHODS: We wanted to evaluate the role of GLUT2 on glucose absorption and glucose homeostasis after intestinal-specific deletion of GLUT2 in mice (GLUT2(ΔIEC) mice). RESULTS: As anticipated, intestinal GLUT2 deletion provoked glucose malabsorption as visualized by the delay in the distribution of oral sugar in tissues...
January 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28123937/fermentable-carbohydrate-stimulates-ffar2-dependent-colonic-pyy-cell-expansion%C3%A2-to%C3%A2-increase-satiety
#17
Lucy Brooks, Alexander Viardot, Anastasia Tsakmaki, Emilie Stolarczyk, Jane K Howard, Patrice D Cani, Amandine Everard, Michelle L Sleeth, Arianna Psichas, Jelena Anastasovskaj, Jimmy D Bell, Kim Bell-Anderson, Charles R Mackay, Mohammad A Ghatei, Stephen R Bloom, Gary Frost, Gavin A Bewick
OBJECTIVE: Dietary supplementation with fermentable carbohydrate protects against body weight gain. Fermentation by the resident gut microbiota produces short-chain fatty acids, which act at free fatty acid receptor 2 (FFAR2). Our aim was to test the hypothesis that FFAR2 is important in regulating the beneficial effects of fermentable carbohydrate on body weight and to understand the role of gut hormones PYY and GLP-1. METHODS: Wild-type or Ffar2(-/-) mice were fed an inulin supplemented or control diet...
January 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28123936/metabolomic-profiling-identifies-potential-pathways-involved-in-the-interaction-of-iron-homeostasis-with-glucose-metabolism
#18
Lars Stechemesser, Sebastian K Eder, Andrej Wagner, Wolfgang Patsch, Alexandra Feldman, Michael Strasser, Simon Auer, David Niederseer, Ursula Huber-Schönauer, Bernhard Paulweber, Stephan Zandanell, Sandra Ruhaltinger, Daniel Weghuber, Elisabeth Haschke-Becher, Christoph Grabmer, Eva Rohde, Christian Datz, Thomas K Felder, Elmar Aigner
OBJECTIVE: Elevated serum ferritin has been linked to type 2 diabetes (T2D) and adverse health outcomes in subjects with the Metabolic Syndrome (MetS). As the mechanisms underlying the negative impact of excess iron have so far remained elusive, we aimed to identify potential links between iron homeostasis and metabolic pathways. METHODS: In a cross-sectional study, data were obtained from 163 patients, allocated to one of three groups: (1) lean, healthy controls (n = 53), (2) MetS without hyperferritinemia (n = 54) and (3) MetS with hyperferritinemia (n = 56)...
January 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28123935/deletion-of-histone-deacetylase-3-in-adult-beta-cells-improves-glucose-tolerance-via-increased-insulin-secretion
#19
Jarrett R Remsberg, Benjamin N Ediger, Wesley Y Ho, Manashree Damle, Zhenghui Li, Christopher Teng, Cristina Lanzillotta, Doris A Stoffers, Mitchell A Lazar
OBJECTIVE: Histone deacetylases are epigenetic regulators known to control gene transcription in various tissues. A member of this family, histone deacetylase 3 (HDAC3), has been shown to regulate metabolic genes. Cell culture studies with HDAC-specific inhibitors and siRNA suggest that HDAC3 plays a role in pancreatic β-cell function, but a recent genetic study in mice has been contradictory. Here we address the functional role of HDAC3 in β-cells of adult mice. METHODS: An HDAC3 β-cell specific knockout was generated in adult MIP-CreERT transgenic mice using the Cre-loxP system...
January 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28123934/circulating-fgf21-in-humans-is-potently-induced-by-short-term-overfeeding-of-carbohydrates
#20
Anne-Marie Lundsgaard, Andreas M Fritzen, Kim A Sjøberg, Lene S Myrmel, Lise Madsen, Jørgen F P Wojtaszewski, Erik A Richter, Bente Kiens
OBJECTIVE: Fibroblast-growth factor 21 (FGF21) is thought to be important in metabolic regulation. Recently, low protein diets have been shown to increase circulating FGF21 levels. However, when energy contribution from dietary protein is lowered, other macronutrients, such as carbohydrates, must be increased to meet eucaloric balance. This raises the possibility that intake of a diet rich in carbohydrates may induce an increase in plasma FGF21 levels per se. Here we studied the role of dietary carbohydrates on the levels of circulating FGF21 and concomitant physiologic effects by feeding healthy men a carbohydrate rich diet without reducing protein intake...
January 2017: Molecular Metabolism
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