The Brain and Leptin Resistance and Implications for Food-Related Disorders



Obesity and the chronic diseases associated with obesity are rapidly becoming a public health crisis in the world. The existence of a circulating factor with effects on body weight has long been anticipated. The discovery of the hormone leptin in 1994 dramatically accelerated the pace of research in obesity and the neurobiology of feeding. Following the initial characterization of leptin, the concept of a peripheral satiety signal gained new credibility. Early research typically focused on the weight-reducing effects of leptin, consequently leading to the idea of leptin as an antiobesity hormone. Subsequent studies, however, have indicated that leptin plays a role in many functions related to energy balance Many insights into leptin function have been gained from rodent models of obesity, which either lack functional leptin or do not respond to its effects due to the mutation in the leptin receptor gene. An obvious and important search has begun to see whether a significant proportion of human obesity can be due to mutations in the ob gene. The coding region of the leptin gene has been sequenced from hundreds of people, but mutations have not been found. Although mutations other than in the coding region may affect leptin messenger RNA, the demonstration that most obese individuals have high circulating leptin levels did exclude the possibility that the problem lied in the ob gene itself. Indeed, human obesity does not appear to be due to impairment in leptin or its receptor. Overweight and obese humans are hyperleptinemic but they seem to be resistant to leptin, which means they do not respond to high levels of leptin in blood. Biological processes potentially involved in leptin resistance include transport of leptin into the brain, alterations of leptin hypothalamic receptor expression, and downstream signaling pathways. This chapter focuses on possible mechanisms that may underlie leptin resistance.


Anorexia Nervosa Eating Disorder Binge Eating Bulimia Nervosa 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



The gene that encodes leptin protein


Obese mouse with a mutation in the leptin gene


The gene that encodes leptin receptor


Obese mouse with a recessive mutation in the leptin receptor gene


Splice variant of the leptin receptor gene


Blood–brain barrier


Cerebrospinal fluid


Body mass index


Janus Kinase, implicated in signaling by leptin


Signal transducer and activator of transcription protein


Suppressor of cytokine signaling


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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Human Neurotransmitters Laboratory, Vascular and Hypertension DivisionBaker IDI Heart and Diabetes InstituteMelbourneAustralia

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