caa a22 4500 44531351X CHVBK 20180317142638.0 cr unu---uuuuu 170323e20110801xx s 000 0 eng 10.1007/s11095-010-0341-1 doi (NATIONALLICENCE)springer-10.1007/s11095-010-0341-1 Witkamp Renger Division of Human Nutrition, Wageningen University, P.O. Box8129, 6700, EV Wageningen, The Netherlands aut Current and Future Drug Targets in Weight Management [Elektronische Daten] [Renger Witkamp] ABSTRACT: Obesity will continue to be one of the leading causes of chronic disease unless the ongoing rise in the prevalence of this condition is reversed. Accumulating morbidity figures and a shortage of effective drugs have generated substantial research activity with several molecular targets being investigated. However, pharmacological modulation of body weight is extremely complex, since it is essentially a battle against one of the strongest human instincts and highly efficient mechanisms of energy uptake and storage. This review provides an overview of the different molecular strategies intended to lower body weight or adipose tissue mass. Weight-loss drugs in development include molecules intended to reduce the absorption of lipids from the GI tract, various ways to limit food intake, and compounds that increase energy expenditure or reduce adipose tissue size. A number of new preparations, including combinations of the existing drugs topiramate plus phentermine, bupropion plus naltrexone, and the selective 5-HT2C agonist lorcaserin have recently been filed for approval. Behind these leading candidates are several other potentially promising compounds and combinations currently undergoing phase II and III testing. Some interesting targets further on the horizon are also discussed. The Author(s), 2010 energy metabolism nationallicence food-intake nationallicence obesity complications nationallicence satiety hormones nationallicence weight management nationallicence 5-HT : serotonin (5-hydroxytryptamine) nationallicence 11β-HSD1 : 11-β hydroxysteroid dehydrogenase type 1 nationallicence AgRP : agouti-related protein nationallicence β3AR : β3-adrenoceptors nationallicence BAT : brown adipose tissue nationallicence BMI : body mass index nationallicence CART : cocaine-amphetamine-regulated transcript nationallicence CB1 : cannabinoid receptor type 1 nationallicence CCK : cholecystokinin nationallicence CNS : central nervous system nationallicence DGAT : diacylglycerol O-acyltransferase nationallicence DPP-IV : dipeptidyl peptidase IV nationallicence EEC : entero-endocrine cell nationallicence GABA : gamma-amino butyrate nationallicence GH : growth hormone nationallicence GI : gastro-intestinal nationallicence GLP-1 : glucagon-like peptide 1 nationallicence HPA(-axis) : hypothalamic-pituitary-adrenal (-axis) nationallicence MCH : melanine-concentrating hormone nationallicence MGAT : 2-acylglycerol O-acyltransferase nationallicence MSH : melanocyte-stimulating hormone nationallicence MTP : microsomal triglyceride transfer protein nationallicence NPY : neuropeptide Y nationallicence OXM : oxyntomodulin nationallicence POMC : pro-opiomelanocortin nationallicence PP : pancreatic polypeptide nationallicence PPAR γ : peroxisome proliferator-activated receptor-γ nationallicence PYY : peptide YY nationallicence SGLT2 : (low affinity) sodium-dependent glucose co-transporter nationallicence TRPV type 1 : transient receptor potential cation channel V type 1 nationallicence Pharmaceutical Research Springer US; http://www.springer-ny.com 28/8(2011-08-01), 1792-1818 0724-8741 28:8<1792 2011 28 11095 https://doi.org/10.1007/s11095-010-0341-1 text/html Onlinezugriff via DOI 1 review-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11095-010-0341-1 text/html Onlinezugriff via DOI NATIONALLICENCE 100 1- Witkamp Renger Division of Human Nutrition, Wageningen University, P.O. Box8129, 6700, EV Wageningen, The Netherlands aut NATIONALLICENCE 773 0- Pharmaceutical Research Springer US; http://www.springer-ny.com 28/8(2011-08-01), 1792-1818 0724-8741 28:8<1792 2011 28 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer