{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T20:54:49Z","timestamp":1793652889403,"version":"4.5.1"},"reference-count":96,"publisher":"American Society for Clinical Investigation","issue":"2","license":[{"start":{"date-parts":[[2023,1,24]],"date-time":"2023-01-24T00:00:00Z","timestamp":1674518400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,1,24]]},"abstract":"<jats:p>\n                    Elevated circulating dipeptidyl peptidase-4 (DPP4) is a biomarker for liver disease, but its involvement in gluconeogenesis and metabolic associated fatty liver disease progression remains unclear. Here, we identified that DPP4 in hepatocytes but not TEK receptor tyrosine kinase\u2013positive endothelial cells regulates the local bioactivity of incretin hormones and gluconeogenesis. However, the complete absence of DPP4 (\n                    <jats:italic>\n                      Dpp4\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    ) in aged mice with metabolic syndrome accelerates liver fibrosis without altering dyslipidemia and steatosis. Analysis of transcripts from the livers of\n                    <jats:italic>\n                      Dpp4\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    mice displayed enrichment for inflammasome, p53, and senescence programs compared with littermate controls. High-fat, high-cholesterol feeding decreased\n                    <jats:italic>Dpp4<\/jats:italic>\n                    expression in F4\/80\n                    <jats:sup>+<\/jats:sup>\n                    cells, with only minor changes in immune signaling. Moreover, in a lean mouse model of severe nonalcoholic fatty liver disease, phosphatidylethanolamine\n                    <jats:italic>N<\/jats:italic>\n                    -methyltransferase mice, we observed a 4-fold increase in circulating DPP4, in contrast with previous findings connecting DPP4 release and obesity. Last, we evaluated DPP4 levels in patients with hepatitis C infection with dysglycemia (Homeostatic Model Assessment of Insulin Resistance &gt; 2) who underwent direct antiviral treatment (with\/without ribavirin). DPP4 protein levels decreased with viral clearance; DPP4 activity levels were reduced at long-term follow-up in ribavirin-treated patients; but metabolic factors did not improve. These data suggest elevations in DPP4 during hepatitis C infection are not primarily regulated by metabolic disturbances.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.154314","type":"journal-article","created":{"date-parts":[[2022,12,6]],"date-time":"2022-12-06T12:01:14Z","timestamp":1670328074000},"source":"Crossref","is-referenced-by-count":20,"title":["Hepatocyte-derived DPP4 regulates portal GLP-1 bioactivity, modulates glucose production, and when absent influences NAFLD progression"],"prefix":"10.1172","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4056-9766","authenticated-orcid":true,"given":"Natasha A.","family":"Trzaskalski","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ontario, Canada."},{"name":"University of Ottawa Heart Institute, Ottawa, Ontario, 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