Leptin pp 67-78 | Cite as

Leptin, Obesity, and Leptin Resistance

  • Heike MünzbergEmail author
  • Steven B. Heymsfield


The cloning of leptin in 1994 was an important milestone in obesity research. In those days obesity was rather stigmatized as a condition caused by lack of character and self-control. With leptin and its receptor being the first single genes that could cause morbid obesity in man and mice, it is now appreciated that obesity is caused by a dysregulation of central neuronal circuits. Unfortunately, the high hopes that leptin would cure obesity were quickly dampened by the discovery that most obese humans have increased leptin levels and develop leptin resistance. It is now hoped that leptin resistance can be overcome by drugs that enhance leptin sensitivity. We review current knowledge of the mechanisms that cause leptin resistance and factors that influence leptin resistance and sensitivity. This topic is further discussed in the context of how and if improvement of leptin resistance can hold the key to cure human obesity.


Leptin receptor STAT3 SOCS3 Hypothalamus Blood–brain barrier Leptin transport Cellular leptin resistance 


ob/ob mice

Leptin-deficient mice

db/db mice

Leptin receptor-deficient mice


Blood–brain barrier


Long form leptin receptor


Cerebrospinal fluid




Tyrosine residues 985/1077/1138


Src homology-2 domain protein




Signal-transducer-and-acti- vator-of transcription-3/5






Phosphotyrosine phospha tase-1B


High-fat diet


Diet-induced obesity


Arcuate nucleus


α-Melanocyte-stimulating hormone


Agouti-related protein




Circumventricular organ


Median eminence


Ventromedial hypothalamus


Endoplasmatic reticulum


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© Springer International Publishing Switzerland 2015

Authors and Affiliations

  1. 1.Pennington Biomedical Research Center, LSU systemBaton RougeUSA

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