Natasha A Trzaskalski, Branka Vulesevic, My-Anh Nguyen, Natasha Jeraj, Evgenia Fadzeyeva, Nadya M Morrow, Cassandra Aa Locatelli, Nicole Travis, Antonio A Hanson, Julia Rc Nunes, Conor O'Dwyer, Jelske N Van der Veen, Ilka Lorenzen-Schmidt, Rick Seymour, Serena M Pulente, Andrew C Clément, Angela M Crawley, René L Jacobs, Mary-Anne Doyle, Curtis L Cooper, Kyoung-Han Kim, Morgan D Fullerton, Erin E Mulvihill
Elevated circulating dipeptidyl-peptidase 4 is a biomarker for liver disease, but its involvement in gluconeogenesis and in metabolic-associated fatty liver disease (MAFLD) progression remains unclear. Here we identified that DPP4 in hepatocytes but not Tie2+ endothelial cells regulates the local bioactivity of incretin hormones and gluconeogenesis. However, the complete absence of DPP4 (Dpp4-/-) in aged mice with metabolic syndrome accelerates liver fibrosis without altering dyslipidemia and steatosis. Analysis of transcripts from the livers of whole body Dpp4-/- displayed enrichment for inflammasome, p53, and senescence programs compared to littermate controls...
December 6, 2022: JCI Insight