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Dipeptidyl peptidase IV (DPP4)-deficiency attenuates diet-induced obesity in rats: possible implications for the hypothalamic neuropeptidergic system.
MedLine Citation:
PMID:  20887754     Owner:  NLM     Status:  In-Process    
Abstract/OtherAbstract:
The underlying mechanisms controlling food intake and satiety are thoroughly controlled, but seem to be insufficient under conditions of almost unlimited food supply. Hence, overweight and obesity are serious problems especially in industrialized countries. To assess the possible influence of CD26, exerting a dipeptidyl peptidase activity (DPP4) cleaving several energy homeostasis-relevant peptides, we investigated wild type and DPP4-deficient dark agouti rats in a model of diet-induced obesity and found a reduced weight gain in DPP4-deficient rats. When investigating the specific increase of whole body fat volume by MRI to assess the distribution pattern (subcutaneous vs. intraabdominal), there was an altered ratio under dietary conditions only in DPP4-deficient rats, which was due to lower intraabdominal fat amounts. Furthermore, we investigated the number of cells immunopositive for the leptin receptor (OB-R), the orexigenic leptin antagonist neuropeptide Y (NPY), as well as of the NPY receptors Y1, Y2, and Y5 within hypothalamic nuclei. Independent from the body weight, higher levels of NPY and all receptors were expressed in DPP4-deficent rats. Under obese conditions, hypothalamic Y2-levels were reduced in both strains. Concerning NPY and Y1, there were partly oppositional effects, with reduced hypothalamic Y1 levels only in wild types, and increased NPY levels only in DPP4-deficient rats. These effects might be responsible for unaltered food intake in DPP4-deficent rats compared to wild types, despite reduced weight gain. However, since the food intake remained unaffected, these effects suggest that DPP4 exerts its effects on intraabdominal fat also via peripheral actions.
Authors:
Michael Stephan; Anna Radicke; Sandra Leutloff; Andreas Schmiedl; Reinhard Pabst; Stephan von Hörsten; Sabine Dettmer; Joachim Lotz; Heike Nave
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-09-29
Journal Detail:
Title:  Behavioural brain research     Volume:  216     ISSN:  1872-7549     ISO Abbreviation:  Behav. Brain Res.     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2010-11-15     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8004872     Medline TA:  Behav Brain Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  712-8     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier B.V. All rights reserved.
Affiliation:
Clinic for Psychosomatics and Psychotherapy, Hannover Medical School, OE 7160, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany. Stephan.Michael@mh-hannover.de
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