TY  - JOUR
A1  - Saussenthaler, Sophie
A1  - Ouni, Meriem
A1  - Baumeier, Christian
A1  - Schwerbel, Kristin
A1  - Gottmann, Pascal
A1  - Christmann, Sabrina
A1  - Laeger, Thomas
A1  - Schürmann, Annette
T1  - Epigenetic regulation of hepatic Dpp4 expression in response to dietary protein
T2  - The journal of nutritional biochemistry
N2  - Dipeptidyl peptidase 4 (DPP4) is known to be elevated in metabolic disturbances such as obesity, type 2 diabetes and fatty liver disease. Lowering DPP4 concentration by pharmacological inhibition improves glucose homeostasis and exhibits beneficial effects to reduce hepatic fat content. As factors regulating the endogenous expression of Dpp4 are unknown, the aim of this study was to examine whether the Dpp4 expression is epigenetically regulated in response to dietary components. Primary hepatocytes were treated with different macronutrients, and Dpp4 mRNA levels and DPP4 activity were evaluated. Moreover, dietary low-protein intervention was conducted in New Zealand obese (NZO) mice, and subsequently, effects on Dpp4 expression, methylation as well as plasma concentration and activity were determined. Our results indicate that Dpp4 mRNA expression is mediated by DNA methylation in several tissues. We therefore consider the Dpp4 southern shore as tissue differentially methylated region. Amino acids increased Dpp4 expression in primary hepatocytes, whereas glucose and fatty acids were without effect. Dietary protein restriction in NZO mice increased Dpp4 DNA methylation in liver leading to diminished Dpp4 expression and consequently to lowered plasma DPP4 activity. We conclude that protein restriction in the adolescent and adult states is a sufficient strategy to reduce DPP4 which in turn contributes to improve glucose homeostasis. (C) 2018 Published by Elsevier Inc.
KW  - DPP4
KW  - DNA methylation
KW  - Protein restriction
KW  - Type 2 diabetes
KW  - NZO
Y1  - 2018
UR  - https://publishup.uni-potsdam.de/frontdoor/index/index/docId/50838
SN  - 0955-2863
SN  - 1873-4847
VL  - 63
SP  - 109
EP  - 116
PB  - Elsevier
CY  - New York
ER  -