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Neurobiology of Obesity

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13 papers 0 to 25 followers
By Ehud Ur Professor and Head, Endocrinology, UBC, Vancouver
Una Fairbrother, Elliot Kidd, Tanya Malagamuwa, Andrew Walley
PURPOSE OF REVIEW: This review aims to present current information on genes underlying severe obesity, with the main emphasis on the three genes LEP, LEPR and MC4R. RECENT FINDINGS: There is a substantial amount of evidence that variants in at least ten different genes are the cause of severe monogenic obesity. The majority of these are involved in the leptin-melanocortin signalling pathway. Due to the frequency of some of the identified variants, it is clear that monogenic variants also make a significant contribution to common obesity...
August 18, 2018: Current Diabetes Reports
Aline Martins de Carvalho, Ping Shao, Huikun Liu, Han-Ling Cheng, Yan Zheng, Junhong Leng, Weiqin Li, Tao Huang, Tiange Wang, Leishen Wang, Shuang Zhang, Gang Hu, Lu Qi
The genetic variants near the Melanocortin-4 receptor gene (MC4R), a key protein regulating energy balance and adiposity, have been related to obesity and glucose metabolism. We aimed to assess whether the MC4R genotype affected longitudinal changes in body weight and glucose metabolism biomarkers among women with prior gestational diabetes mellitus (GDM). The MC4R genotype, postpartum weight reduction, and glycemic changes between after delivery and pregnancy were assessed in a cohort of 1208 Chinese women who had experienced GDM...
August 29, 2017: Scientific Reports
Priya Sumithran, Luke A Prendergast, Elizabeth Delbridge, Katrina Purcell, Arthur Shulkes, Adamandia Kriketos, Joseph Proietto
BACKGROUND: After weight loss, changes in the circulating levels of several peripheral hormones involved in the homeostatic regulation of body weight occur. Whether these changes are transient or persist over time may be important for an understanding of the reasons behind the high rate of weight regain after diet-induced weight loss. METHODS: We enrolled 50 overweight or obese patients without diabetes in a 10-week weight-loss program for which a very-low-energy diet was prescribed...
October 27, 2011: New England Journal of Medicine
Karen K Ryan, Valentina Tremaroli, Christoffer Clemmensen, Petia Kovatcheva-Datchary, Andriy Myronovych, Rebekah Karns, Hilary E Wilson-Pérez, Darleen A Sandoval, Rohit Kohli, Fredrik Bäckhed, Randy J Seeley
Bariatric surgical procedures, such as vertical sleeve gastrectomy (VSG), are at present the most effective therapy for the treatment of obesity, and are associated with considerable improvements in co-morbidities, including type-2 diabetes mellitus. The underlying molecular mechanisms contributing to these benefits remain largely undetermined, despite offering the potential to reveal new targets for therapeutic intervention. Substantial changes in circulating total bile acids are known to occur after VSG. Moreover, bile acids are known to regulate metabolism by binding to the nuclear receptor FXR (farsenoid-X receptor, also known as NR1H4)...
May 8, 2014: Nature
Stephan J Guyenet, Hong T Nguyen, Bang H Hwang, Michael W Schwartz, Denis G Baskin, Joshua P Thaler
Astrocytes respond to multiple forms of central nervous system (CNS) injury by entering a reactive state characterized by morphological changes and a specific pattern of altered protein expression. Termed astrogliosis, this response has been shown to strongly influence the injury response and functional recovery of CNS tissues. This pattern of CNS inflammation and injury associated with astrogliosis has recently been found to occur in the energy homeostasis centers of the hypothalamus during diet-induced obesity (DIO) in rodent models, but the characterization of the astrocyte response remains incomplete...
May 28, 2013: Brain Research
Joshua P Thaler, Stephan J Guyenet, Mauricio D Dorfman, Brent E Wisse, Michael W Schwartz
No abstract text is available yet for this article.
August 2013: Diabetes
Deniz Atasoy, J Nicholas Betley, Wei-Ping Li, Helen H Su, Sinem M Sertel, Louis K Scheffer, Julie H Simpson, Richard D Fetter, Scott M Sternson
Synaptic connectivity and molecular composition provide a blueprint for information processing in neural circuits. Detailed structural analysis of neural circuits requires nanometer resolution, which can be obtained with serial-section electron microscopy. However, this technique remains challenging for reconstructing molecularly defined synapses. We used a genetically encoded synaptic marker for electron microscopy (GESEM) based on intra-vesicular generation of electron-dense labeling in axonal boutons. This approach allowed the identification of synapses from Cre recombinase-expressing or GAL4-expressing neurons in the mouse and fly with excellent preservation of ultrastructure...
December 2014: Nature Neuroscience
Adam E Locke, Bratati Kahali, Sonja I Berndt, Anne E Justice, Tune H Pers, Felix R Day, Corey Powell, Sailaja Vedantam, Martin L Buchkovich, Jian Yang, Damien C Croteau-Chonka, Tonu Esko, Tove Fall, Teresa Ferreira, Stefan Gustafsson, Zoltán Kutalik, Jian'an Luan, Reedik Mägi, Joshua C Randall, Thomas W Winkler, Andrew R Wood, Tsegaselassie Workalemahu, Jessica D Faul, Jennifer A Smith, Jing Hua Zhao, Wei Zhao, Jin Chen, Rudolf Fehrmann, Åsa K Hedman, Juha Karjalainen, Ellen M Schmidt, Devin Absher, Najaf Amin, Denise Anderson, Marian Beekman, Jennifer L Bolton, Jennifer L Bragg-Gresham, Steven Buyske, Ayse Demirkan, Guohong Deng, Georg B Ehret, Bjarke Feenstra, Mary F Feitosa, Krista Fischer, Anuj Goel, Jian Gong, Anne U Jackson, Stavroula Kanoni, Marcus E Kleber, Kati Kristiansson, Unhee Lim, Vaneet Lotay, Massimo Mangino, Irene Mateo Leach, Carolina Medina-Gomez, Sarah E Medland, Michael A Nalls, Cameron D Palmer, Dorota Pasko, Sonali Pechlivanis, Marjolein J Peters, Inga Prokopenko, Dmitry Shungin, Alena Stančáková, Rona J Strawbridge, Yun Ju Sung, Toshiko Tanaka, Alexander Teumer, Stella Trompet, Sander W van der Laan, Jessica van Setten, Jana V Van Vliet-Ostaptchouk, Zhaoming Wang, Loïc Yengo, Weihua Zhang, Aaron Isaacs, Eva Albrecht, Johan Ärnlöv, Gillian M Arscott, Antony P Attwood, Stefania Bandinelli, Amy Barrett, Isabelita N Bas, Claire Bellis, Amanda J Bennett, Christian Berne, Roza Blagieva, Matthias Blüher, Stefan Böhringer, Lori L Bonnycastle, Yvonne Böttcher, Heather A Boyd, Marcel Bruinenberg, Ida H Caspersen, Yii-Der Ida Chen, Robert Clarke, E Warwick Daw, Anton J M de Craen, Graciela Delgado, Maria Dimitriou, Alex S F Doney, Niina Eklund, Karol Estrada, Elodie Eury, Lasse Folkersen, Ross M Fraser, Melissa E Garcia, Frank Geller, Vilmantas Giedraitis, Bruna Gigante, Alan S Go, Alain Golay, Alison H Goodall, Scott D Gordon, Mathias Gorski, Hans-Jörgen Grabe, Harald Grallert, Tanja B Grammer, Jürgen Gräßler, Henrik Grönberg, Christopher J Groves, Gaëlle Gusto, Jeffrey Haessler, Per Hall, Toomas Haller, Goran Hallmans, Catharina A Hartman, Maija Hassinen, Caroline Hayward, Nancy L Heard-Costa, Quinta Helmer, Christian Hengstenberg, Oddgeir Holmen, Jouke-Jan Hottenga, Alan L James, Janina M Jeff, Åsa Johansson, Jennifer Jolley, Thorhildur Juliusdottir, Leena Kinnunen, Wolfgang Koenig, Markku Koskenvuo, Wolfgang Kratzer, Jaana Laitinen, Claudia Lamina, Karin Leander, Nanette R Lee, Peter Lichtner, Lars Lind, Jaana Lindström, Ken Sin Lo, Stéphane Lobbens, Roberto Lorbeer, Yingchang Lu, François Mach, Patrik K E Magnusson, Anubha Mahajan, Wendy L McArdle, Stela McLachlan, Cristina Menni, Sigrun Merger, Evelin Mihailov, Lili Milani, Alireza Moayyeri, Keri L Monda, Mario A Morken, Antonella Mulas, Gabriele Müller, Martina Müller-Nurasyid, Arthur W Musk, Ramaiah Nagaraja, Markus M Nöthen, Ilja M Nolte, Stefan Pilz, Nigel W Rayner, Frida Renstrom, Rainer Rettig, Janina S Ried, Stephan Ripke, Neil R Robertson, Lynda M Rose, Serena Sanna, Hubert Scharnagl, Salome Scholtens, Fredrick R Schumacher, William R Scott, Thomas Seufferlein, Jianxin Shi, Albert Vernon Smith, Joanna Smolonska, Alice V Stanton, Valgerdur Steinthorsdottir, Kathleen Stirrups, Heather M Stringham, Johan Sundström, Morris A Swertz, Amy J Swift, Ann-Christine Syvänen, Sian-Tsung Tan, Bamidele O Tayo, Barbara Thorand, Gudmar Thorleifsson, Jonathan P Tyrer, Hae-Won Uh, Liesbeth Vandenput, Frank C Verhulst, Sita H Vermeulen, Niek Verweij, Judith M Vonk, Lindsay L Waite, Helen R Warren, Dawn Waterworth, Michael N Weedon, Lynne R Wilkens, Christina Willenborg, Tom Wilsgaard, Mary K Wojczynski, Andrew Wong, Alan F Wright, Qunyuan Zhang, Eoin P Brennan, Murim Choi, Zari Dastani, Alexander W Drong, Per Eriksson, Anders Franco-Cereceda, Jesper R Gådin, Ali G Gharavi, Michael E Goddard, Robert E Handsaker, Jinyan Huang, Fredrik Karpe, Sekar Kathiresan, Sarah Keildson, Krzysztof Kiryluk, Michiaki Kubo, Jong-Young Lee, Liming Liang, Richard P Lifton, Baoshan Ma, Steven A McCarroll, Amy J McKnight, Josine L Min, Miriam F Moffatt, Grant W Montgomery, Joanne M Murabito, George Nicholson, Dale R Nyholt, Yukinori Okada, John R B Perry, Rajkumar Dorajoo, Eva Reinmaa, Rany M Salem, Niina Sandholm, Robert A Scott, Lisette Stolk, Atsushi Takahashi, Toshihiro Tanaka, Ferdinand M van 't Hooft, Anna A E Vinkhuyzen, Harm-Jan Westra, Wei Zheng, Krina T Zondervan, Andrew C Heath, Dominique Arveiler, Stephan J L Bakker, John Beilby, Richard N Bergman, John Blangero, Pascal Bovet, Harry Campbell, Mark J Caulfield, Giancarlo Cesana, Aravinda Chakravarti, Daniel I Chasman, Peter S Chines, Francis S Collins, Dana C Crawford, L Adrienne Cupples, Daniele Cusi, John Danesh, Ulf de Faire, Hester M den Ruijter, Anna F Dominiczak, Raimund Erbel, Jeanette Erdmann, Johan G Eriksson, Martin Farrall, Stephan B Felix, Ele Ferrannini, Jean Ferrières, Ian Ford, Nita G Forouhi, Terrence Forrester, Oscar H Franco, Ron T Gansevoort, Pablo V Gejman, Christian Gieger, Omri Gottesman, Vilmundur Gudnason, Ulf Gyllensten, Alistair S Hall, Tamara B Harris, Andrew T Hattersley, Andrew A Hicks, Lucia A Hindorff, Aroon D Hingorani, Albert Hofman, Georg Homuth, G Kees Hovingh, Steve E Humphries, Steven C Hunt, Elina Hyppönen, Thomas Illig, Kevin B Jacobs, Marjo-Riitta Jarvelin, Karl-Heinz Jöckel, Berit Johansen, Pekka Jousilahti, J Wouter Jukema, Antti M Jula, Jaakko Kaprio, John J P Kastelein, Sirkka M Keinanen-Kiukaanniemi, Lambertus A Kiemeney, Paul Knekt, Jaspal S Kooner, Charles Kooperberg, Peter Kovacs, Aldi T Kraja, Meena Kumari, Johanna Kuusisto, Timo A Lakka, Claudia Langenberg, Loic Le Marchand, Terho Lehtimäki, Valeriya Lyssenko, Satu Männistö, André Marette, Tara C Matise, Colin A McKenzie, Barbara McKnight, Frans L Moll, Andrew D Morris, Andrew P Morris, Jeffrey C Murray, Mari Nelis, Claes Ohlsson, Albertine J Oldehinkel, Ken K Ong, Pamela A F Madden, Gerard Pasterkamp, John F Peden, Annette Peters, Dirkje S Postma, Peter P Pramstaller, Jackie F Price, Lu Qi, Olli T Raitakari, Tuomo Rankinen, D C Rao, Treva K Rice, Paul M Ridker, John D Rioux, Marylyn D Ritchie, Igor Rudan, Veikko Salomaa, Nilesh J Samani, Jouko Saramies, Mark A Sarzynski, Heribert Schunkert, Peter E H Schwarz, Peter Sever, Alan R Shuldiner, Juha Sinisalo, Ronald P Stolk, Konstantin Strauch, Anke Tönjes, David-Alexandre Trégouët, Angelo Tremblay, Elena Tremoli, Jarmo Virtamo, Marie-Claude Vohl, Uwe Völker, Gérard Waeber, Gonneke Willemsen, Jacqueline C Witteman, M Carola Zillikens, Linda S Adair, Philippe Amouyel, Folkert W Asselbergs, Themistocles L Assimes, Murielle Bochud, Bernhard O Boehm, Eric Boerwinkle, Stefan R Bornstein, Erwin P Bottinger, Claude Bouchard, Stéphane Cauchi, John C Chambers, Stephen J Chanock, Richard S Cooper, Paul I W de Bakker, George Dedoussis, Luigi Ferrucci, Paul W Franks, Philippe Froguel, Leif C Groop, Christopher A Haiman, Anders Hamsten, Jennie Hui, David J Hunter, Kristian Hveem, Robert C Kaplan, Mika Kivimaki, Diana Kuh, Markku Laakso, Yongmei Liu, Nicholas G Martin, Winfried März, Mads Melbye, Andres Metspalu, Susanne Moebus, Patricia B Munroe, Inger Njølstad, Ben A Oostra, Colin N A Palmer, Nancy L Pedersen, Markus Perola, Louis Pérusse, Ulrike Peters, Chris Power, Thomas Quertermous, Rainer Rauramaa, Fernando Rivadeneira, Timo E Saaristo, Danish Saleheen, Naveed Sattar, Eric E Schadt, David Schlessinger, P Eline Slagboom, Harold Snieder, Tim D Spector, Unnur Thorsteinsdottir, Michael Stumvoll, Jaakko Tuomilehto, André G Uitterlinden, Matti Uusitupa, Pim van der Harst, Mark Walker, Henri Wallaschofski, Nicholas J Wareham, Hugh Watkins, David R Weir, H-Erich Wichmann, James F Wilson, Pieter Zanen, Ingrid B Borecki, Panos Deloukas, Caroline S Fox, Iris M Heid, Jeffrey R O'Connell, David P Strachan, Kari Stefansson, Cornelia M van Duijn, Gonçalo R Abecasis, Lude Franke, Timothy M Frayling, Mark I McCarthy, Peter M Visscher, André Scherag, Cristen J Willer, Michael Boehnke, Karen L Mohlke, Cecilia M Lindgren, Jacques S Beckmann, Inês Barroso, Kari E North, Erik Ingelsson, Joel N Hirschhorn, Ruth J F Loos, Elizabeth K Speliotes
Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes...
February 12, 2015: Nature
Miyuki Shibata, Ryoichi Banno, Mariko Sugiyama, Takashi Tominaga, Takeshi Onoue, Taku Tsunekawa, Yoshinori Azuma, Daisuke Hagiwara, Wenjun Lu, Yoshihiro Ito, Motomitsu Goto, Hidetaka Suga, Yoshihisa Sugimura, Yutaka Oiso, Hiroshi Arima
Agouti-related protein (AgRP) expressed in the arcuate nucleus is a potent orexigenic neuropeptide, which increases food intake and reduces energy expenditure resulting in increases in body weight (BW). Glucocorticoids, key hormones that regulate energy balance, have been shown in rodents to regulate the expression of AgRP. In this study, we generated AgRP-specific glucocorticoid receptor (GR)-deficient (knockout [KO]) mice. Female and male KO mice on a high-fat diet (HFD) showed decreases in BW at the age of 6 weeks compared with wild-type mice, and the differences remained significant until 16 weeks old...
April 2016: Endocrinology
Yan Gao, Zhonggang Li, J Scott Gabrielsen, Judith A Simcox, Soh-hyun Lee, Deborah Jones, Bob Cooksey, Gregory Stoddard, William T Cefalu, Donald A McClain
Dietary iron supplementation is associated with increased appetite. Here, we investigated the effect of iron on the hormone leptin, which regulates food intake and energy homeostasis. Serum ferritin was negatively associated with serum leptin in a cohort of patients with metabolic syndrome. Moreover, the same inverse correlation was observed in mice fed a high-iron diet. Adipocyte-specific loss of the iron exporter ferroportin resulted in iron loading and decreased leptin, while decreased levels of hepcidin in a murine hereditary hemochromatosis (HH) model increased adipocyte ferroportin expression, decreased adipocyte iron, and increased leptin...
September 2015: Journal of Clinical Investigation
Sirazum M Choudhury, Tricia M Tan, Stephen R Bloom
PURPOSE OF REVIEW: Pandemic obesity is the most pressing health issue of this century. The most successful treatment so far is bariatric surgery, but for various reasons, surgery cannot be applied to all patients who require treatment. Gastrointestinal hormones are likely to play a key role in the success of bariatric surgery. This article examines in detail three of these gut hormones: peptide YY, oxyntomodulin and pancreatic polypeptide, and reviews how recent developments may offer new targets for therapy...
February 2016: Current Opinion in Endocrinology, Diabetes, and Obesity
Darleen Sandoval, Stephanie R Sisley
Type 2 diabetes is often treated with a class of drugs referred to as glucagon-like peptide-1 (GLP-1) analogs. GLP-1 is a peptide secreted by the gut that acts through only one known receptor, the GLP-1 receptor. The primary function of GLP-1 is thought to be lowering of postprandial glucose levels. Indeed, medications utilizing this system, including the long-acting GLP-1 analogs liraglutide and exenatide, are beneficial in reducing both blood sugars and body weight. GLP-1 analogs were long presumed to affect glucose control through their ability to increase insulin levels through peripheral action on beta cells...
December 15, 2015: Molecular and Cellular Endocrinology
Garron T Dodd, Stephanie Decherf, Kim Loh, Stephanie E Simonds, Florian Wiede, Eglantine Balland, Troy L Merry, Heike Münzberg, Zhong-Yin Zhang, Barbara B Kahn, Benjamin G Neel, Kendra K Bence, Zane B Andrews, Michael A Cowley, Tony Tiganis
The primary task of white adipose tissue (WAT) is the storage of lipids. However, "beige" adipocytes also exist in WAT. Beige adipocytes burn fat and dissipate the energy as heat, but their abundance is diminished in obesity. Stimulating beige adipocyte development, or WAT browning, increases energy expenditure and holds potential for combating metabolic disease and obesity. Here, we report that insulin and leptin act together on hypothalamic neurons to promote WAT browning and weight loss. Deletion of the phosphatases PTP1B and TCPTP enhanced insulin and leptin signaling in proopiomelanocortin neurons and prevented diet-induced obesity by increasing WAT browning and energy expenditure...
January 15, 2015: Cell
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