This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Jeong, K.-H. Articles by Majzoub, J. A. Search for Related Content PubMed PubMed Citation Articles by Jeong, K.-H. Articles by Majzoub, J. A. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Substance via MeSH

Impaired Leptin Expression and Abnormal Response to Fasting in Corticotropin-Releasing Hormone-Deficient Mice

Division of Endocrinology (K.-H.J., S.S., J.A.M.), Children’s Hospital, and Division of Endocrinology, Diabetes, and Hypertension (K.-H.J.), Brigham and Women’s Hospital, Harvard Medical School; and Department of Biology (E.P.W.), Boston University, Boston, Massachusetts 02215

Address all correspondence and requests for reprints to: Joseph A. Majzoub, Division of Endocrinology, Children’s Hospital, Harvard Medical School, Enders 416, 300 Longwood Avenue, Boston, Massachusetts 02115. E-mail: joseph.majzoub{at}tch.harvard.edu.

Leptin has been postulated to comprise part of an adipostat, whereby during states of excessive energy storage, elevated levels of the hormone prevent further weight gain by inhibiting appetite. A physiological role for leptin in this regard remains unclear because the presence of excessive food, and therefore the need to restrain overeating under natural conditions, is doubtful. We have previously shown that CRH-deficient (Crh^–/–) mice have glucocorticoid insufficiency and lack the fasting-induced increase in glucocorticoid, a hormone important in stimulating leptin synthesis and secretion. We hypothesized that these mice might have low circulating leptin. Indeed, Crh^–/– mice exhibited no diurnal variation of leptin, whereas normal littermates showed a clear rhythm, and their leptin levels were lower than their counterparts. A continuous peripheral CRH infusion to Crh^–/– mice not only restored corticosterone levels, but it also increased leptin expression to normal. Surprisingly, 36 h of fasting elevated leptin levels in Crh^–/– mice, rather than falling as in normal mice. This abnormal leptin change during fasting in Crh^–/– mice was corrected by corticosterone replacement. Furthermore, Crh^–/– mice lost less body weight during 24 h of fasting and ate less food during refeeding than normal littermates. Taken together, we conclude that glucocorticoid insufficiency in Crh^–/– mice results in impaired leptin production as well as an abnormal increase in leptin during fasting, and propose that the fast-induced physiological reduction in leptin may play an important role to stimulate food intake during the recovery from fasting.

This article has been cited by other articles:

				J. Gay, E. Kokkotou, M. O'Brien, C. Pothoulakis, and K. P. Karalis Corticotropin-Releasing Hormone Deficiency Is Associated with Reduced Local Inflammation in a Mouse Model of Experimental Colitis Endocrinology, July 1, 2008; 149(7): 3403 - 3409. [Abstract] [Full Text] [PDF]

				J. A Majzoub Corticotropin-releasing hormone physiology Eur. J. Endocrinol., November 1, 2006; 155(suppl_1): S71 - S76. [Abstract] [Full Text] [PDF]

				R. Malcher-Lopes, S. Di, V. S. Marcheselli, F.-J. Weng, C. T. Stuart, N. G. Bazan, and J. G. Tasker Opposing crosstalk between leptin and glucocorticoids rapidly modulates synaptic excitation via endocannabinoid release. J. Neurosci., June 14, 2006; 26(24): 6643 - 6650. [Abstract] [Full Text] [PDF]

				M. C. Henson and V. D. Castracane Leptin in Pregnancy: An Update Biol Reprod, February 1, 2006; 74(2): 218 - 229. [Abstract] [Full Text] [PDF]