Gliptins Suppress Inflammatory Macrophage Activation to Mitigate Inflammation, Fibrosis, Oxidative Stress, and Vascular Dysfunction in Models of Nonalcoholic Steatohepatitis and Liver Fibrosis

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RESEARCH PRODUCT

Gliptins Suppress Inflammatory Macrophage Activation to Mitigate Inflammation, Fibrosis, Oxidative Stress, and Vascular Dysfunction in Models of Nonalcoholic Steatohepatitis and Liver Fibrosis

Sebastian Steven S.-y. Weng X.-y. Wang Thomas Klein Detlef Schuppan Detlef Schuppan Michael Hausding Andreas Daiber Yong Ook Kim

subject

0301 basic medicine medicine.medical_specialty Physiology Clinical Biochemistry Anti-Inflammatory Agents Gene Expression Inflammation Type 2 diabetes 030204 cardiovascular system & hematology medicine.disease_cause Biochemistry Antioxidants Proinflammatory cytokine Mice 03 medical and health sciences 0302 clinical medicine Non-alcoholic Fatty Liver Disease Fibrosis Internal medicine medicine Animals Myeloid Cells Molecular Biology Dipeptidyl peptidase-4 General Environmental Science Inflammation Mice Knockout Dipeptidyl-Peptidase IV Inhibitors business.industry Macrophages Cell Biology Macrophage Activation medicine.disease Fibrosis Diet Disease Models Animal Oxidative Stress 030104 developmental biology Endocrinology Liver NADPH Oxidase 2 General Earth and Planetary Sciences Tumor necrosis factor alpha Steatosis medicine.symptom Reactive Oxygen Species business Biomarkers Oxidative stress

description

Abstract Aims: Nonalcoholic steatohepatitis (NASH) is characterized by steatosis, panlobular inflammation, liver fibrosis, and increased cardiovascular mortality. Dipeptidyl peptidase-4 inhibitors (gliptins) are indirect glucagon-like peptide 1 agonists with antidiabetic and anti-inflammatory activity, used for the treatment of type 2 diabetes. Their potential and underlying mechanisms to treat metabolic liver inflammation and fibrosis as well as the associated vascular dysfunction remain to be explored. Results: In the methionine/choline-deficient (MCD) diet and Mdr2−/− models of NASH and liver fibrosis, treatment with sitagliptin and linagliptin significantly decreased parameters of steatosis and inflammation, which was accompanied by suppression of hepatic transcript levels reflecting metabolic inflammation and fibrosis, including SREBP-1c, FAS, TNFα, iNOS, α-SMA, Col1α1, and MMP-12. Moreover, gliptins reduced the number of liver infiltrating CD11b+Ly6Chi proinflammatory monocytes/macrophages and liver...

year	journal	country	edition	language
2017-06-22	Antioxidants & Redox Signaling

https://doi.org/10.1089/ars.2016.6953