Mendelian obesity, molecular pathways and pharmacological therapies: a review.

In this qualitative review we analyze the major pathways and mechanisms involved in the onset of genetically-determined obesity (Mendelian obesity), identifying possible pharmacological treatments and trials. We searched PubMed with the keywords (obesity[Title/Abstract]) AND mutation[Title/Abstract], and OMIM with the keyword "obesity". In both cases, we selected non-syndromic Mendelian obesity. We then searched ClinicalTrials.gov with the following criteria: "recruitment status: active, not recruiting and completed"; "study type: interventional (clinical trial)"; "study results: with results"; type of intervention: "drug or dietary supplement". From the PubMed and OMIM searches we obtained a total of 15 genes associated with monogenic Mendelian obesity. From ClinicalTrials.gov we retrieved 46 completed or active trials of pharmacological treatments. We summarized the molecular bases of Mendelian obesity and searched for any clinical trials completed or underway for the treatment of severe forms of obesity. Most Mendelian obesities are linked to dysfunctions in the leptin/melanocortin signaling pathway, and most of the possible drugs target this pathway in order to improve energy expenditure and reduce food intake.