Olivia M Farr1, Anna Gavrieli, Christos S Mantzoros. 1. Division of Endocrinology, Boston VA Healthcare System/Harvard Medical School Section of Endocrinology, Beth-Israel Deaconess Medical Center/Harvard Medical School, Boston, Massachusetts, USA *Olivia M. Farr and Anna Gavrieli authors have contributed equally to the writing of this article.
Abstract
PURPOSE OF REVIEW: To summarize previous and current advancements for leptin therapeutics, we described how leptin may be useful in leptin deficient states such as lipodystrophy, for which leptin was recently approved, and how it may be useful in the future for typical obesity. RECENT FINDINGS: The discovery of leptin in 1994 built the foundation for understanding the pathophysiology and treatment of obesity. Leptin therapy reverses morbid obesity related to congenital leptin deficiency and appears to possibly treat lipodystrophy, a finding which has led to the approval of leptin for the treatment of lipodystrophy in the USA and Japan. Typical obesity, on the other hand, is characterized by hyperleptinemia and leptin tolerance. Thus, leptin administration has proven ineffective for inducing weight loss on its own but could possibly be useful in combination with other therapies or for weight loss maintenance. SUMMARY: Leptin is not able to treat typical obesity; however, it is effective for reversing leptin deficiency-induced obesity and is possibly useful in lipodystrophy. New mechanisms and pathways involved in leptin resistance are continuously discovered, whereas the development of new techniques and drug combinations which may improve leptin's efficacy and safety regenerate the hope for its use as an effective treatment for typical obesity.
PURPOSE OF REVIEW: To summarize previous and current advancements for leptin therapeutics, we described how leptin may be useful in leptin deficient states such as lipodystrophy, for which leptin was recently approved, and how it may be useful in the future for typical obesity. RECENT FINDINGS: The discovery of leptin in 1994 built the foundation for understanding the pathophysiology and treatment of obesity. Leptin therapy reverses morbid obesity related to congenital leptin deficiency and appears to possibly treat lipodystrophy, a finding which has led to the approval of leptin for the treatment of lipodystrophy in the USA and Japan. Typical obesity, on the other hand, is characterized by hyperleptinemia and leptin tolerance. Thus, leptin administration has proven ineffective for inducing weight loss on its own but could possibly be useful in combination with other therapies or for weight loss maintenance. SUMMARY:Leptin is not able to treat typical obesity; however, it is effective for reversing leptindeficiency-induced obesity and is possibly useful in lipodystrophy. New mechanisms and pathways involved in leptin resistance are continuously discovered, whereas the development of new techniques and drug combinations which may improve leptin's efficacy and safety regenerate the hope for its use as an effective treatment for typical obesity.
Authors: Harry R Kissileff; John C Thornton; Migdalia I Torres; Katherine Pavlovich; Laurel S Mayer; Vamsi Kalari; Rudolph L Leibel; Michael Rosenbaum Journal: Am J Clin Nutr Date: 2012-01-11 Impact factor: 7.045
Authors: Sharon H Chou; John P Chamberland; Xiaowen Liu; Giuseppe Matarese; Chuanyun Gao; Rianna Stefanakis; Mary T Brinkoetter; Huizhi Gong; Kalliopi Arampatzi; Christos S Mantzoros Journal: Proc Natl Acad Sci U S A Date: 2011-04-04 Impact factor: 11.205
Authors: Alexander J Rodríguez; Teresa Neeman; Aaron G Giles; Claudio A Mastronardi; Gilberto Paz Filho Journal: Arq Bras Endocrinol Metabol Date: 2014-11-01
Authors: Y C Loraine Tung; Pawan Gulati; Che-Hsiung Liu; Debra Rimmington; Rowena Dennis; Marcella Ma; Vladimir Saudek; Stephen O'Rahilly; Anthony P Coll; Giles S H Yeo Journal: Mol Metab Date: 2015-02-07 Impact factor: 7.422
Authors: Michael V Fedewa; Elizabeth D Hathaway; Christie L Ward-Ritacco; Tyler D Williams; Ward C Dobbs Journal: Sports Med Date: 2018-06 Impact factor: 11.136