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The Genetics of Obesity the Genetics of Obesity Journal of Obesity Journal of Obesity The Genetics of Obesity The Genetics of Obesity Journal of Obesity The Genetics of Obesity Copyright © 2012 Hindawi Publishing Corporation. All rights reserved. This is a focus issue published in “Journal of Obesity.” All articles are open access articles distributed under the Creative Commons At- tribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Editorial Board DavidB.Allison,USA Xu Feng Huang, Australia Jonatan R. Ruiz, Sweden B. J. Ammori, UK Terr y Huang , USA Jordi Salas-Salvado,´ Spain Marco Anselmino, Italy Gianluca Iacobellis, Canada Francesco Saverio Papadia, Italy Molly S. Bray, USA Lauren E. Lissner, Sweden J. C. Seidell, The Netherlands Bernhard Breier, New Zealand Yannis Manios, Greece G. Silecchia, Italy Eliot Brinton, USA Claude Marcus, Sweden Laurence Tecott, USA Yvon Chagnon, Canada Ron F. Morrison, USA Serena Tonstad, Norway Karen Charlton, Australia Michael M. Murr, USA Paul Trayhurn, UK Eric Doucet, Canada Tomoo Okada, Japan Rob Martinus Van Dam, Singapore Pietro Forestieri, Italy Renato Pasquali, Italy Youfa Wang, USA Jayne Fulkerson, USA Mark A. Pereira, USA Aron Weller, Israel Jesus´ M. Garagorri, Spain Angelo Pietrobelli, Italy Aimin Xu, Hong Kong Tiffany L. Gary-Webb, USA R. Prager, Austria Jack A. Yanovski, USA Andras Hajnal, USA Denis Richard, Canada Alfredo Halpern, Brazil Robert J. Ross, Canada Contents The Role of Leptin in Antipsychotic-Induced Weight Gain: Genetic and Non-Genetic Factors, Fabio Panariello, Gina Polsinelli, Carol Borlido, Marcellino Monda, and Vincenzo De Luca Volume 2012, Article ID 572848, 7 pages High Levels of Cardiovascular Risk Factors among Pakistanis in Norway Compared to Pakistanis in Pakistan, Naeem Zahid, Haakon E. Meyer, Bernadette N. Kumar, Bjørgulf Claussen, and Akhtar Hussain Volume 2011, Article ID 163749, 5 pages Mendelian Randomisation Study of Childhood BMI and Early Menarche, Hannah S. Mumby, Cathy E. Elks, Shengxu Li, Stephen J. Sharp, Kay-Tee Khaw, Robert N. Luben, Nicholas J. Wareham, Ruth J. F. Loos, and Ken K. Ong Volume 2011, Article ID 180729, 6 pages An Obesity Risk SNP (rs17782313) near the MC4R Gene Is Associated with Cerebrocortical Insulin Resistance in Humans, Otto Tschritter, Axel Haupt, Hubert Preissl, Caroline Ketterer, Anita M. Hennige, Tina Sartorius, Fausto Machicao, Andreas Fritsche, and Hans-Ulrich Haring¨ Volume 2011, Article ID 283153, 4 pages Sequence Analysis of the UCP1 Gene in a Severe Obese Population from Southern Italy, Giuseppe Labruna, Fabrizio Pasanisi, Giuliana Fortunato, Carmela Nardelli, Carmine Finelli, Eduardo Farinaro, Franco Contaldo, and Lucia Sacchetti Volume 2011, Article ID 269043, 4 pages Genetics of Childhood Obesity, Jianhua Zhao and Struan F. A. Grant Volume 2011, Article ID 845148, 9 pages Studies of Gene Variants Related to Inflammation, Oxidative Stress, Dyslipidemia, and Obesity: Implications for a Nutrigenetic Approach, Maira Ladeia R. Curti, Patri’cia Jacob, Maria Carolina Borges, Marcelo Macedo Rogero, and Sandra Roberta G. Ferreira Volume 2011, Article ID 497401, 31 pages Variations in Adipokine Genes AdipoQ, Lep, and LepR Are Associated with Risk for Obesity-Related Metabolic Disease: The Modulatory Role of Gene-Nutrient Interactions, Jennifer Emily Enns, Carla G. Taylor, and Peter Zahradka Volume 2011, Article ID 168659, 17 pages Associations of FTO and MC4R Variants with Obesity Traits in Indians and the Role of Rural/Urban Environment as a Possible Effect Modifier, A. E. Taylor, M. N. Sandeep, C. S. Janipalli, C. Giambartolomei, D. M. Evans, M. V. Kranthi Kumar, D. G. Vinay, P. Smitha, V. Gupta, M. Aruna, S. Kinra, R. M. Sullivan, L. Bowen, N. J. Timpson, G. Davey Smith, F. Dudbridge, D. Prabhakaran, Y. Ben-Shlomo, K. S. Reddy, S. Ebrahim, and G. R. Chandak Volume 2011, Article ID 307542, 7 pages Can Thrifty Gene(s) or Predictive Fetal Programming for Thriftiness Lead to Obesity?, Ulfat Baig, Prajakta Belsare, Milind Watve, and Maithili Jog Volume 2011, Article ID 861049, 11 pages Differential Effects of Calorie Restriction and Exercise on the Adipose Transcriptome in Diet-Induced Obese Mice, Karrie E. Wheatley, Leticia M. Nogueira, Susan N. Perkins, and Stephen D. Hursting Volume 2011, Article ID 265417, 13 pages Microarray Evidences the Role of Pathologic Adipose Tissue in Insulin Resistance and Their Clinical Implications, Sandeep Kumar Mathur, Priyanka Jain, and Prashant Mathur Volume 2011, Article ID 587495, 16 pages Genetic Variance in Uncoupling Protein 2 in Relation to Obesity, Type 2 Diabetes, and Related Metabolic Traits: Focus on the Functional −866G>A Promoter Variant (rs659366), Louise T. Dalgaard Volume 2011, Article ID 340241, 12 pages Relationships of Adrenoceptor Polymorphisms with Obesity, Kazuko Masuo and Gavin W. Lambert Volume 2011, Article ID 609485, 10 pages Interleukin-15, IL-15 Receptor-Alpha, and Obesity: Concordance of Laboratory Animal and Human Genetic Studies, LeBris S. Quinn and Barbara G. Anderson Volume 2011, Article ID 456347, 8 pages Rs9939609 Variant of the Fat Mass and Obesity-Associated Gene and Trunk Obesity in Adolescents, Harald Mangge, Wilfried Renner, Gunter Almer, Daniel Weghuber, Reinhard Moller,¨ and Renate Horejsi Volume 2011, Article ID 186368, 4 pages Gene by Sex Interaction for Measures of Obesity in the Framingham Heart Study, Ashlee M. Benjamin, Sunil Suchindran, Kaela Pearce, Jennifer Rowell, Lillian F. Lien, John R. Guyton, and Jeanette J. McCarthy Volume 2011, Article ID 329038, 8 pages Hindawi Publishing Corporation Journal of Obesity Volume 2012, Article ID 572848, 7 pages doi:10.1155/2012/572848 Review Article TheRoleofLeptininAntipsychotic-InducedWeightGain: Genetic and Non-Genetic Factors Fabio Panariello,1 Gina Polsinelli,2 Carol Borlido,2 Marcellino Monda,3 andVincenzoDeLuca2, 4 1 Spedali Civili Brescia, Department Mental Health, 25123 Brescia, Italy 2 Centre for Addiction and Mental Health, room 30, 250 College street, Toronto, ON, Canada M5T 1R8 3 Dipartimento di Medicina Sperimentale, Seconda Universita` degli Studi di Napoli, 80131 Napoli, Italy 4 Department of Psychiatry, University of Toronto, Toronto, ON, Canada M5T 1R8 Correspondence should be addressed to Vincenzo De Luca, vincenzo [email protected] Received 2 January 2011; Revised 3 October 2011; Accepted 13 October 2011 Academic Editor: Angelo Pietrobelli Copyright © 2012 Fabio Panariello et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Schizophrenia is a chronic and disabling mental illness affecting millions of people worldwide. A greater proportion of people with schizophrenia tends to be overweight. Antipsychotic medications have been considered the primary risk factor for obesity in schizophrenia, although the mechanisms by which they increase weight and produce metabolic disturbances are unclear. Several lines of research indicate that leptin could be a good candidate involved in pathways linking antipsychotic treatment and weight gain. Leptin is a circulating hormone released by adipocytes in response to increased fat deposition to regulate body weight, acting through receptors in the hypothalamus. In this work, we reviewed preclinical, clinical, and genetic data in order to infer the potential role played by leptin in antipsychotic-induced weight gain considering two main hypotheses: (1) leptin is an epiphenomenon of weight gain; (2) leptin is a consequence of antipsychotic-induced “leptin-resistance status,” causing weight gain. 1. Background The increased use of atypical antipsychotics over the last decade has raised concerns about their metabolic side effects, Schizophrenia has a worldwide prevalence of about one per- such as weight gain, diabetes, and dyslipidemia [4]. In ad- cent and has the potential for devastating emotional, phys- dition, medication-induced weight gain has been associated ical, and mental consequences [1]. Antipsychotic drugs are with a lower quality of life and noncompliance, which in- the first line of treatment for those with schizophrenia and creases the risk for relapse. The higher risk of cardiovascular other psychoses [2]. There are two classes of antipsychotic disease, leading to enhanced morbidity, mortality, significant medications used for treatment referred to as either typical or atypical. Typical antipsychotic drugs, like haloperidol, act economic cost, reduced quality of life, and lower compliance as high-affinity antagonists for dopamine 2 (D2) receptors to treatment can be linked to the obesitogenic and diabeto- with a possibility of extrapyramidal side effects. genic capacity of these drugs [5]. Second-generation antipsychotics (SGAs), like olanzap- However, the mechanisms of weight gain and dyslipi- ine and clozapine, have lower incidences of extrapyramidal demia are poorly understood, and various parts of the en- side effects than typical antipsychotics because they are po- docrine system are presumably involved in these side effects. tent antagonists of serotonin 2A (5-HT2A) rather than D2 Several lines of evidence indicate that antipsychotic drugs receptor antagonists, with a higher affinity for the former. elicit weight gain in some, but not all, individuals, suggesting These drugs also inhibit the G-protein-coupled receptors for a genetic predisposition [5]. Several hypotheses with regard several other biogenic amines including cholinergic, adrener- to the
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