Leptin signaling as a therapeutic target of obesity

Abstract

Introduction: Leptin is a hormone with a key role in food intake and body weight homeostasis. Congenital leptin deficiency (CLD) is a rare disease that causes hyperphagia and early severe obesity. However, common obesity conditions are associated with hyperleptinemia and leptin resistance.

Areas covered: The main signaling pathways activated by leptin as well as the mechanisms underlying the regulatory actions of leptin on food intake and on lipid and glucose metabolism are reviewed. The potential mechanisms involving leptin resistance and the main regulatory hormonal and nutritional factors controlling leptin production/functions are also analyzed. The pathophysiology of leptin in human obesity, and especially the trials analyzing effects of leptin replacement therapy in patients with CLD or in subjects with common obesity and in post-obese weight-reduced subjects are also summarized.

Expert opinion: The use of drugs or specific bioactive food components with anti-inflammatory properties to reduce the inflammatory state associated with obesity, especially at the hypothalamus, may help to overcome leptin resistance. Research should also be focused on investigating dietary strategies, food supplements or drugs capable of avoiding or reversing the leptin fall during weight management, in order to promote sustained body weight lowering and weight loss maintenance.

Keywords:

• inflammation
• leptin
• nutrients
• obesity

Declaration of interest

The authors were supported by the Ministry of Economy and Competitiveness (AGL 2009-10873/ALI and BFU2012-36089) and CIBERobn of the government of Spain, Navarra government and Linea Especial ‘Nutrition Obesidad y Salud’ University of Navarra. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

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