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Am J Physiol Endocrinol Metab 296: E282-E290, 2009. First published November 18, 2008; doi:10.1152/ajpendo.90523.2008
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Central and peripheral effects of chronic food restriction and weight restoration in the rat

Kimberly P. Kinzig, Sara L. Hargrave, and Erin E. Tao

Ingestive Behavior Research Center, Department of Psychological Sciences, Purdue University, West Lafayette, Indiana

Submitted 20 June 2008 ; accepted in final form 15 November 2008

Previous studies have demonstrated that some endocrine consequences of long-term caloric restriction persist after weight restoration in human subjects. Here we evaluate effects of chronic food restriction in rats that were restricted to 70% of control kcal for 4 wk and subsequently weight restored. Measures were taken from rats at 80% (chronically restricted; CR), 90% (partially weight restored; PR), 100% (fully weight restored; FR), and after 4 wk at 100% body weight of controls (extended weight restored; ER). Plasma insulin and leptin were decreased, and ghrelin was increased in CR compared with controls. Leptin and ghrelin normalized with weight restoration at PR, FR, and ER; however, baseline insulin was not normalized until the ER state. Hypothalamic mRNA expression levels for proopiomelanocortin (POMC), agouti-related protein (AgRP), and neuropeptide Y (NPY) revealed significantly less POMC mRNA expression in CR and PR rats, and significantly less arcuate NPY mRNA in PR and FR. In the dorsomedial hypothalamus, CR, PR, and FR rats had significantly increased NPY expression that was not normalized until the ER state. In response to a test meal, insulin and ghrelin release patterns were altered through the FR stage, and ghrelin remained affected at ER. Collectively, these data demonstrate that mere weight restoration is not sufficient to normalize hypothalamic gene expression levels and endocrine responses to a meal, and that meal-related ghrelin responses persist despite weight restoration for up to 4 wk.

ghrelin; insulin; leptin; hypothalamus



Address for reprint requests and other correspondence: K. P. Kinzig, 703 Third St., Dept. of Psychological Sciences, Purdue Univ., West Lafayette, IN 47907 (e-mail: kkinzig{at}psych.purdue.edu)







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