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Am J Clin Nutr 89: 985S-990S, 2009. First published January 28, 2009; doi:10.3945/ajcn.2008.26788D
American Journal of Clinical Nutrition, doi:10.3945/ajcn.2008.26788D
Vol. 89, No. 3, 985S-990S, March 2009

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© 2009 American Society for Clinical Nutrition

ORIGINAL RESEARCH COMMUNICATION

From observation to experimentation: leptin action in the mediobasal hypothalamus

Kevin W Williams1,2,3,4, Michael M Scott1,2,3,4 and Joel K Elmquist1,2,3,4

1 From the Division of Hypothalamic Research, Departments of Internal Medicine and Pharmacology, The University of Texas Southwestern Medical Center, Dallas, TX.

2 Presented at the symposium "Leptin: Weight Management and Beyond," held at Experimental Biology 2008, San Diego, CA, 6 April 2008.

3 Supported by the NIH (F32 DK077487-01 to KWW; DK53301, MH61583, DK081185, and DK71320 to JKE) and by an American Diabetes Association Smith Family Foundation Pinnacle Program Award to JKE.

4 Reprints not available. Address correspondence to JK Elmquist, Division of Hypothalamic Research, Departments of Internal Medicine and Pharmacology, The University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 85390-9051. E-mail: joel.elmquist{at}utsouthwestern.edu.

The burgeoning obesity epidemic has fueled the drive to describe, mechanistically, metabolic homeostasis. From the early theories implicating glucose as a principal modulator grew an understanding of a complex array of metabolic signals, sensed by peripheral organs along with specific locations within the central nervous system (CNS). The discovery that leptin, an adipose-derived hormone, acts within the mediobasal hypothalamus to control food intake and energy expenditure ushered in a decade of research that went on to describe not only the specific nuclei and cell type, such as proopiomelanocortin neurons of the arcuate nucleus, that respond to leptin but also the signaling cascades that mediated its effects. This review thus highlights the sites and mechanisms of action of leptin, both in the hypothalamus and in extrahypothalamic sites within the CNS, and shows our current knowledge and direction of future research aimed at understanding the multifunctional role of leptin in maintaining metabolic homeostasis.




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