Leptin signaling as a therapeutic target of obesity.
BACKGROUND
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.


METHODS
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.


CONCLUSIONS
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.
University of Navarra, Centre for Nutrition Research, School of Pharmacy , C/Irunlarrea 1, 31008 Pamplona , Spain.
Neira
N
Sáinz
Carlos J
CJ
González-Navarro
J Alfredo
JA
Martínez
Maria J
MJ
Moreno-Aliaga
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D019440:Anti-Obesity Agents / Q000494:pharmacology*; D001835:Body Weight; D006801:Humans; D007031:Hypothalamus / Q000187:drug effects; D007249:Inflammation / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D020738:Leptin / Q000172:deficiency / Q000378:metabolism*; D058990:Molecular Targeted Therapy; D009765:Obesity / Q000188:drug therapy* / Q000503:physiopathology; D015398:Signal Transduction / Q000187:drug effects
D000893:Anti-Inflammatory Agents; D019440:Anti-Obesity Agents; D020738:Leptin
inflammation; leptin; nutrients; obesity