Management of Monogenic and Syndromic Obesity.

Similar to the general population, lifestyle interventions focused on nutrition and physical activity form the foundation for treating obesity caused by rare genetic disorders. Additional therapies, including metreleptin and setmelanotide, that target defects within the leptin signaling pathway can effectively synergize with lifestyle efforts to treat monogenic disorders of leptin, leptin receptor, proopiomelanocortin (POMC), and proprotein convertase subtilisin/kexin type 1 (PCSK1) and syndromic conditions, such as the ciliopathies Bardet-Biedl and Alström syndromes, whose pathophysiological mechanisms also converge on the leptin pathway. Investigational treatments for Prader-Willi syndrome target specific defects caused by reduced expression of paternally derived genes within the chromosome 15q region.
Competing Interests: Disclosure J.C. Han is a clinical trial investigator for multi-site research studies sponsored by Rhythm Pharmaceuticals. A.M. Haqq is a clinical trial investigator for multi-site research studies sponsored by Rhythm Pharmaceuticals, Levo Therapeutics, and Eli Lilly. She has received grants from the Weston Family Microbiome Initiative and Canadian Institutes of Health Research, Canada, payment as a speaker for Pfizer Canada, and is a member of advisory boards for Pfizer, Rhythm Pharmaceuticals, and Novo Nordisk Canada. The remaining authors have no disclosures.
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