Document Detail

Blocking dopamine D2 receptors by haloperidol curtails the beneficial impact of calorie restriction on the metabolic phenotype of high-fat diet induced obese mice.
MedLine Citation:
PMID:  21062378     Owner:  NLM     Status:  In-Process    
Calorie restriction is the most effective way of expanding life-span and decreasing morbidity. It improves insulin sensitivity and delays the age-related loss of dopamine receptor D(2) (DRD2) expression in the brain. Conversely, high-fat feeding is associated with obesity, insulin resistance and a reduced number of DRD2 binding sites. We hypothesised that the metabolic benefit of calorie restriction involves the preservation of appropriate DRD2 transmission. The food intake of wild-type C57Bl6 male mice was restricted to 60% of ad lib. intake while they were treated with the DRD2 antagonist haloperidol or vehicle using s.c. implanted pellets. Mice with ad lib. access to food receiving vehicle treatment served as controls. All mice received high-fat food throughout the experiment. After 10 weeks, an i.p. glucose tolerance test was performed and, after 12 weeks, a hyperinsulinaemic euglycaemic clamp. Hypothalamic DRD2 binding was also determined after 12 weeks of treatment. Calorie-restricted (CR) vehicle mice were glucose tolerant and insulin sensitive compared to ad lib. (AL) fed vehicle mice. CR mice treated with haloperidol were slightly heavier than vehicle treated CR mice. Haloperidol completely abolished the beneficial impact of calorie restriction on glucose tolerance and partly reduced the insulin sensitivity observed in CR vehicle mice. The metabolic differences between AL and CR vehicle mice were not accompanied by alterations in hypothalamic DRD2 binding. In conclusion, blocking DRD2 curtails the metabolic effects of calorie restriction. Although this suggests that the dopaminergic system could be involved in the metabolic benefits of calorie restriction, restricting access to high-fat food does not increase (hypothalamic) DRD2 binding capacity, which argues against this inference.
J E de Leeuw van Weenen; H E Auvinen; E T Parlevliet; C P Coomans; J P Schröder-van der Elst; O C Meijer; H Pijl
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of neuroendocrinology     Volume:  23     ISSN:  1365-2826     ISO Abbreviation:  J. Neuroendocrinol.     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-01-11     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8913461     Medline TA:  J Neuroendocrinol     Country:  England    
Other Details:
Languages:  eng     Pagination:  158-67     Citation Subset:  IM    
Copyright Information:
© 2011 The Authors. Journal of Neuroendocrinology © 2011 Blackwell Publishing Ltd.
Department of Endocrinology and Metabolic Diseases, Leiden University Medical Centre, Leiden, The Netherlands.
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