ArticleMolecular metabolism2017
Elevated hepatic DPP4 activity promotes insulin resistance and non-alcoholic fatty liver disease.
Article in Molecular metabolism, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
90 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Dipeptidyl peptidase-4 inhibitors alleviate cognitive dysfunction in type 2 diabetes mellitus.Lipids in health and disease · 2023Pooled it
- Effect of glimepiride versus teneligliptin in combination with metformin in type 2 diabetes mellitus patients.Indian journal of pharmacology · 2024Trial
- Plasma levels of DPP4 activity and sDPP4 are dissociated from inflammation in mice and humans.Nature communications · 2020Trial
- Depletion of myeloid-derived Zbtb46Journal of advanced research · 2026Article
- Exploring Active Ingredients and Mechanisms ofMolecules (Basel, Switzerland) · 2026Article
- DPP4 inhibition affects metabolism and inflammation associated pathways in hiPSC-derived steatotic HLCs.Frontiers in cell and developmental biology · 2026Article
- The liver-muscle axis in metabolic dysfunction-associated steatotic liver disease: a narrative review and conceptual framework for body-composition phenotyping.Frontiers in medicine · 2026Review
- Phenotypic Screening Coupled with AI-Driven Target Deconvolution Identifies α-Terthienyl as a Dual DPP-IV/HSD17β13 Modulator with Efficacy in a Mouse Model of MASLD.bioRxiv : the preprint server for biology · 2025Article
- Oxidative Stress in Liver Metabolic Dysfunction and Diseases, with a Focus on Hepatogenic Diabetes: Effect of Alcohol Consumption.Antioxidants (Basel, Switzerland) · 2025Review
- Comparative effectiveness of antidiabetic therapies on hepatic decompensation in patients with type 2 diabetes: A target trial emulation.JHEP reports : innovation in hepatology · 2025Article
- Unraveling the Antihyperglycemic Effects of Dipeptyl Peptidase-4 Inhibitors in Rodents: A Multi-Faceted Approach Combining Effects on Glucose Homeostasis, Molecular Docking, and ADMET Profiling.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Protective effect of exercise on metabolic dysfunction‑associated fatty liver disease: Potential epigenetic mechanisms (Review).International journal of molecular medicine · 2025Review
- Elimination of hepatocyte-derived DPP4 downregulates cardiac immune- and collagen-related genes but does not alter cardiac function in aged male mice.Physiological reports · 2025Article
- Bridging the gap in obesity research: A consensus statement from the European Society for Clinical Investigation.European journal of clinical investigation · 2025Review
- Review Article: GLP-1 Receptor Agonists and Glucagon/GIP/GLP-1 Receptor Dual or Triple Agonists-Mechanism of Action and Emerging Therapeutic Landscape in MASLD.Alimentary pharmacology & therapeutics · 2025Review
- Clinical Insights into Non-Alcoholic Fatty Liver Disease and the Therapeutic Potential of Flavonoids: An Update.Nutrients · 2025Review
- The Safety and Efficacy of Dietary Epigallocatechin Gallate Supplementation for the Management of Obesity and Non-Alcoholic Fatty Liver Disease: Recent Updates.Biomedicines · 2025Review
- The Triad of Risk: Linking MASLD, Cardiovascular Disease and Type 2 Diabetes; From Pathophysiology to Treatment.Journal of clinical medicine · 2025Review
- The role of microbiota in nonalcoholic fatty liver disease: mechanism of action and treatment strategy.Frontiers in microbiology · 2025Review
- Association of metabolic-dysfunction associated steatotic liver disease with polycystic ovary syndrome.iScience · 2024Review
30 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveIncreased hepatic expression of dipeptidyl peptidase 4 (DPP4) is associated with non-alcoholic fatty liver disease (NAFLD). Whether this is causative for the development of NAFLD is not yet clarified. Here we investigate the effect of hepatic DPP4 overexpression on the development of liver steatosis in a mouse model of diet-induced obesity.
methodsPlasma DPP4 activity of subjects with or without NAFLD was analyzed. Wild-type (WT) and liver-specific Dpp4 transgenic mice (Dpp4-Liv-Tg) were fed a high-fat diet and characterized for body weight, body composition, hepatic fat content and insulin sensitivity. In vitro experiments on HepG2 cells and primary mouse hepatocytes were conducted to validate cell autonomous effects of DPP4 on lipid storage and insulin sensitivity.
resultsSubjects suffering from insulin resistance and NAFLD show an increased plasma DPP4 activity when compared to healthy controls. Analysis of Dpp4-Liv-Tg mice revealed elevated systemic DPP4 activity and diminished active GLP-1 levels. They furthermore show increased body weight, fat mass, adipose tissue inflammation, hepatic steatosis, liver damage and hypercholesterolemia. These effects were accompanied by increased expression of PPARγ and CD36 as well as severe insulin resistance in the liver. In agreement, treatment of HepG2 cells and primary hepatocytes with physiological concentrations of DPP4 resulted in impaired insulin sensitivity independent of lipid content.
conclusionsOur results give evidence that elevated expression of DPP4 in the liver promotes NAFLD and insulin resistance. This is linked to reduced levels of active GLP-1, but also to auto- and paracrine effects of DPP4 on hepatic insulin signaling.
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