title: The melanocortin-4 receptor as target for obesity treatment: a systematic review of emerging pharmacological therapeutic options.
abstract: Obesity is one of the greatest public health challenges of the 21st century. Obesity is currently responsible for ∼0.7-2.8% of a country's health costs worldwide. Treatment is often not effective because weight regulation is complex. Appetite and energy control are regulated in the brain. Melanocortin-4 receptor (MC4R) has a central role in this regulation. MC4R defects lead to a severe clinical phenotype with lack of satiety and early-onset severe obesity. Preclinical research has been carried out to understand the mechanism of MC4R regulation and possible effectors. The objective of this study is to systematically review the literature for emerging pharmacological obesity treatment options. A systematic literature search was performed in PubMed and Embase for articles published until June 2012. The search resulted in 664 papers matching the search terms, of which 15 papers remained after elimination, based on the specific inclusion and exclusion criteria. In these 15 papers, different MC4R agonists were studied in vivo in animal and human studies. Almost all studies are in the preclinical phase. There are currently no effective clinical treatments for MC4R-deficient obese patients, although MC4R agonists are being developed and are entering phase I and II trials.
authors.affiliation: Department of Pediatrics, Division of Endocrinology, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: L
authors.initials: L
authors.lastname: Fani
authors.affiliation: Department of Pediatrics, Division of Endocrinology, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: S
authors.initials: S
authors.lastname: Bak
authors.affiliation: Department of Internal Medicine, Division of Endocrinology, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: P
authors.initials: P
authors.lastname: Delhanty
authors.affiliation: Department of Internal Medicine, Division of Endocrinology, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: E F C
authors.initials: EF
authors.lastname: van Rossum
authors.affiliation: Department of Pediatrics, Division of Endocrinology, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: E L T
authors.initials: EL
authors.lastname: van den Akker
mesh_terms: D000081:Acetamides / Q000627:therapeutic use; D000818:Animals; D019440:Anti-Obesity Agents / Q000627:therapeutic use*; D001069:Appetite Regulation / Q000187:drug effects* / Q000235:genetics; D015992:Body Mass Index; D002149:Energy Intake / Q000187:drug effects* / Q000235:genetics; D004734:Energy Metabolism / Q000187:drug effects* / Q000235:genetics; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D009765:Obesity / Q000188:drug therapy* / Q000235:genetics; D010456:Peptides, Cyclic / Q000627:therapeutic use; D010641:Phenotype; D011759:Pyrrolidines / Q000627:therapeutic use; D044105:Receptor, Melanocortin, Type 4 / Q000819:agonists* / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism; D013141:Spiro Compounds / Q000627:therapeutic use; D000521:alpha-MSH / Q000031:analogs & derivatives / Q000627:therapeutic use
chemical_list: D000081:Acetamides; D019440:Anti-Obesity Agents; C553253:MK-0489; C545557:N-1-(2-(1-(tert-butyl-4-(2,4-difluorophenyl)pyrrolidin-3-yl)-5-chlorophenyl)ethyl)acetamide; D010456:Peptides, Cyclic; D011759:Pyrrolidines; D044105:Receptor, Melanocortin, Type 4; D011956:Receptors, Cell Surface; D013141:Spiro Compounds; C079282:melanotan-II; D000521:alpha-MSH