Epigenetic regulation of hepatic Dpp4 expression in response to dietary protein

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 r...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of nutritional biochemistry 2019-01, Vol.63, p.109-116
Main Authors: Saussenthaler, Sophie, Ouni, Meriem, Baumeier, Christian, Schwerbel, Kristin, Gottmann, Pascal, Christmann, Sabrina, Laeger, Thomas, Schürmann, Annette
Format: Article
Language:English
Subjects:
Amino Acids - pharmacology
Animals
CpG Islands
Dietary Proteins - pharmacology
Dipeptidyl Peptidase 4 - genetics
Dipeptidyl Peptidase 4 - metabolism
DNA methylation
DNA Methylation - drug effects
DPP4
Epigenesis, Genetic
Gene Expression Regulation - drug effects
Hepatocytes - drug effects
Hepatocytes - metabolism
Male
Mice, Inbred C57BL
Mice, Obese
NZO
Protein restriction
Type 2 diabetes
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0955-2863
1873-4847
DOI:10.1016/j.jnutbio.2018.09.025