Obesity is associated with increased levels of soluble Dipeptidyl Peptidase-4 (DPP-4) in serum leading to adipose tissue inflammation and insulin resistance. Animal studies, however, have shown that a high fat diet acutely decreases serum DDP-4 levels. This study investigated the response of serum DDP-4 to a sudden switch from a healthy isocaloric low fat diet to an isocaloric high fat diet (HFD) in healthy human twins. 35 monzyogotic and 11 dizygotic healthy pairs of twins (women and men, age 18 - 70) were investigated for 12 weeks. An isocaloric diet rich in carbohydrates (55% carbohydrates, 30% fat, 15% protein, LF) was applied for 6 weeks, followed by an isocaloric diet rich in saturated fat (40% carbohydrates, 45% fat, 15% protein, HF) for another 6 weeks. Body weight (BW) and serum concentrations of DPP-4, tumor necrosis factor α (TNFα) and insulin were analyzed after the LF period, after one week (HF1w) and at the end (HF6w) of the HF period. Total body fat and lean mass were determined by DEXA-Scan at LF and HF6w. BW was constant over the time of intervention. Serum DPP-4 protein was decreased by 15% at HF1w and by 18% at HF6w, respectively, compared to LF (both P<0.001). At HF1w DPP-4 and TNFα serum levels were positively correlated (r=0.299, P=0.004) however, this correlation was lost at HF6w. Serum DPP-4 was positively correlated with lean mass at LF (r=0.357, P<0.001) and HF6w (r=0.218, P<0.05), however not with body fat content. DPP-4 serum protein was strongly positively correlated within monzogotic twins at LF, HF1w and HF6w (for all P<0.01), but not within dizygotic twins. Insulin was increased 1.20-fold and 1.12-fold at HF1w and HF6w, respectively, compared to LF (both P<0.001). These data indicate that serum DPP-4 protein responds to nutritional stimuli and is decreased upon consuming a HFD under isocaloric conditions in healthy human subjects which is in contrast to overt adiposity. Moreover, expression of serum DPP-4 protein is genetically determined.
M. Kruse: None. A. Ost: None. S. Hornemann: None. D. Hoffmann: None. T. Frahnow: None. A. Busjahn: None. A.F. Pfeiffer: None.
German Federal Ministry of Education and Research (0315424)