Dipeptidyl peptidase IV (DPP4)-deficiency attenuates diet-induced obesity in rats: possible implications for the hypothalamic neuropeptidergic system.
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.
Stephan
Michael
M
Clinic for Psychosomatics and Psychotherapy, Hannover Medical School, OE 7160, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany. Stephan.Michael@mh-hannover.de
Radicke
Anna
A
Leutloff
Sandra
S
Schmiedl
Andreas
A
Pabst
Reinhard
R
von Hörsten
Stephan
S
Dettmer
Sabine
S
Lotz
Joachim
J
Nave
Heike
H
D000818:Animals; D001069:Appetite Regulation / Q000235:genetics / Q000502:physiology; D004041:Dietary Fats / Q000378:metabolism; D018819:Dipeptidyl Peptidase 4 / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D004195:Disease Models, Animal; D002149:Energy Intake / Q000235:genetics; D055786:Gene Knockout Techniques; D050152:Intra-Abdominal Fat / Q000502:physiology*; D008297:Male; D009478:Neuropeptide Y / Q000378:metabolism*; D009765:Obesity / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D017476:Receptors, Neuropeptide Y / Q000378:metabolism; D015430:Weight Gain / Q000235:genetics* / Q000502:physiology
D004041:Dietary Fats; D009478:Neuropeptide Y; D017476:Receptors, Neuropeptide Y; D018819:Dipeptidyl Peptidase 4