HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 89/3/991S    most recent ajcn.2008.26788Ev1 Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Blüher, S. Articles by Mantzoros, C. S Search for Related Content PubMed PubMed Citation Articles by Blüher, S. Articles by Mantzoros, C. S Agricola Articles by Blüher, S. Articles by Mantzoros, C. S

Leptin in humans: lessons from translational research

¹ From the Hospital for Children and Adolescents, University of Leipzig, Germany (SB), and the Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (CSM).

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

³ Supported by NIH grants DK 58785 and 79929 (CSM).

⁴ Reprints not available. Address correspondence to CS Mantzoros, Division of Endocrinology, RN 325, Beth Israel Deaconess Medical Center, Harvard Medical School, 99 Brookline Avenue, Boston, MA 02215. E-mail: cmantzor{at}caregroup.harvard.edu.

Leptin has emerged over the past decade as a key hormone in not only the regulation of food intake and energy expenditure but also in the regulation of neuroendocrine and immune function as well as the modulation of glucose and fat metabolism as shown by numerous observational and interventional studies in humans with (complete) congenital or relative leptin deficiency. These results have led to proof-of-concept studies that have investigated the effect of leptin administration in subjects with complete (congenital) leptin deficiency caused by mutations in the leptin gene as well as in humans with relative leptin deficiency, including states of lipoatrophy or negative energy balance and neuroendocrine dysfunction, as for instance seen with hypothalamic amenorrhea in states of exercise-induced weight loss. In those conditions, most neuroendocrine, metabolic, or immune disturbances can be restored by leptin administration. Leptin replacement therapy is thus a promising approach in several disease states, including congenital complete leptin deficiency, states of energy deprivation, including anorexia nervosa or milder forms of hypothalamic amenorrhea, as well as syndromes of insulin resistance seen in conditions such as congenital or acquired lipodystrophy. In contrast, states of energy excess such as garden-variety obesity are associated with hyperleptinemia that reflects either leptin tolerance or leptin resistance. For those conditions, development of leptin sensitizers is currently a focus of pharmaceutical research. This article summarizes our current understanding of leptin's role in human physiology and its potential role as a novel therapeutic option in human disease states associated with a new hormone deficiency, ie, leptin deficiency.

This article has been cited by other articles:

				E. Lebenthal Introduction to the symposium Am. J. Clinical Nutrition, March 1, 2009; 89(3): 971S - 972S. [Full Text] [PDF]

				K. W Williams, M. M Scott, and J. K Elmquist From observation to experimentation: leptin action in the mediobasal hypothalamus Am. J. Clinical Nutrition, March 1, 2009; 89(3): 985S - 990S. [Abstract] [Full Text] [PDF]

				J. M Friedman Leptin at 14 y of age: an ongoing story Am. J. Clinical Nutrition, March 1, 2009; 89(3): 973S - 979S. [Abstract] [Full Text] [PDF]

				I S. Farooqi and S. O'Rahilly Leptin: a pivotal regulator of human energy homeostasis Am. J. Clinical Nutrition, March 1, 2009; 89(3): 980S - 984S. [Abstract] [Full Text] [PDF]