Hepatic DPP4 DNA methylation associates with fatty liver

Research output: Contribution to journalArticle

Abstract

Hepatic DPP4 expression is elevated in subjects with ectopic fat accumulation in the liver. However, whether increased dipeptidyl peptidase 4 (DPP4) is involved in the pathogenesis or is rather a consequence ofmetabolic disease is not known. We therefore studied the transcriptional regulation of hepatic Dpp4 in young mice prone to diet-induced obesity. Already at 6 weeks of age, expression of hepatic Dpp4 was increased in mice with high weight gain, independent of liver fat content. In the same animals, methylation of four intronic CpG sites was decreased, amplifying glucose-induced transcription of hepatic Dpp4. In older mice, hepatic triglyceride content was increased only in animals with elevated Dpp4 expression. Expression and release of DPP4 were markedly higher in the liver compared with adipose depots. Analysis of human liver biopsy specimens revealed a correlation of DPP4 expression and DNA methylation to stages of hepatosteatosis and nonalcoholic steatohepatitis. In summary, our results indicate a crucial role of the liver in participation to systemic DPP4 levels. Furthermore, the data show that glucoseinduced expression of Dpp4 in the liver is facilitated by demethylation of the Dpp4 gene early in life. This might contribute to early deteriorations in hepatic function, which in turn result in metabolic disease such as hepatosteatosis later in life.

Details

Authors
  • Christian Baumeier
  • Sophie Saussenthaler
  • Anne Kammel
  • Markus Jähnert
  • Luisa Schlüter
  • Deike Hesse
  • Mickaël Canouil
  • Stephane Lobbens
  • Robert Caiazzo
  • Violeta Raverdy
  • François Pattou
  • Emma Nilsson
  • Jussi Pihlajamäki
  • Charlotte Ling
  • Philippe Froguel
  • Annette Schürmann
  • Robert W. Schwenk
Organisations
External organisations
  • German Center for Diabetes Research
  • European Genome Institute for Diabetes (EGID) UMR 8199
  • Lille University Hospital
  • Kuopio University Hospital
  • Hammersmith Hospital
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Gastroenterology and Hepatology
Original languageEnglish
Pages (from-to)25-35
Number of pages11
JournalDiabetes
Volume66
Issue number1
Publication statusPublished - 2017 Jan 1
Publication categoryResearch
Peer-reviewedYes