ArticleNature2018
Hepatocyte-secreted DPP4 in obesity promotes adipose inflammation and insulin resistance.
Article in Nature, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 163 papers, 7 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
163 citing papers in PubMed, 7 syntheses or guidelines pooled it, 289 citations in OpenAlex.
- [Recent Advances in the Interorgan Regulatory Roles of Adipose Tissue].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2026Pooled it
- The predictive value of a body shape index as a novel obesity metric for cancer risk: a systematic review and meta-analysis.Frontiers in nutrition · 2025Pooled it
- Effect of dipeptidyl peptidase-4 inhibitors on tumor necrosis factor alpha levels in patients with type 2 diabetes mellitus.European journal of medical research · 2024Pooled it
- New Mediators in the Crosstalk between Different Adipose Tissues.International journal of molecular sciences · 2024Pooled it
- Dipeptidyl peptidase-4 inhibitors alleviate cognitive dysfunction in type 2 diabetes mellitus.Lipids in health and disease · 2023Pooled it
- Dipeptidyl-peptidase-4 inhibitors have anti-inflammatory effects in patients with type 2 diabetes.European journal of clinical pharmacology · 2023Pooled it
- DPP-4 inhibitors may improve the mortality of coronavirus disease 2019: A meta-analysis.PloS one · 2021Pooled it
- Plasma levels of DPP4 activity and sDPP4 are dissociated from inflammation in mice and humans.Nature communications · 2020Trial
- Favourable effect of the sodium-glucose co-transporter-2 inhibitor canagliflozin plus the dipeptidyl peptidase-4 inhibitor teneligliptin in combination on glycaemic fluctuation: An open-label, prospective, randomized, parallel-group comparison trial (the CALMER study).Diabetes, obesity & metabolism · 2020Trial
- Association of DPP4 with esophageal stricture progression and the Hippo-YAP pathway.Animal models and experimental medicine · 2026Article
- Article
- Depletion of myeloid-derived Zbtb46Journal of advanced research · 2026Article
- Epithelial TMPRSS2 impairs glucose homeostasis in obese mice by regulating ghrelin-GLP-1 receptor signaling pathway.JCI insight · 2026Article
- The Role of Dipeptidyl Peptidase Inhibitors in Pulmonary Diseases.Biomedicines · 2026Review
- Therapeutic targeting of blood-derived protein infiltration to modulate neuroinflammation in cerebellar ataxia.Journal of neuroinflammation · 2026Article
- DPP4 inhibition affects metabolism and inflammation associated pathways in hiPSC-derived steatotic HLCs.Frontiers in cell and developmental biology · 2026Article
- Effects of metabolic syndrome on pulmonary infection in pediatric bronchial asthma: a narrative review.Frontiers in pediatrics · 2026Review
- A rationally designed 18-amino acid peptide with potential as GLP-1 receptor agonist.Frontiers in pharmacology · 2026Article
- Anti-diabetic medications and cancer: links beyond glycemic and body weight control.Precision clinical medicine · 2025Review
- Association between dietary inflammatory index and hepatic steatosis: cross-sectional evidence from the NHANES 2007-2020.Journal of health, population, and nutrition · 2025Article
103 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Obesity-induced metabolic disease involves functional integration among several organs via circulating factors, but little is known about crosstalk between liver and visceral adipose tissue (VAT). In obesity, VAT becomes populated with inflammatory adipose tissue macrophages (ATMs). In obese humans, there is a close correlation between adipose tissue inflammation and insulin resistance, and in obese mice, blocking systemic or ATM inflammation improves insulin sensitivity. However, processes that promote pathological adipose tissue inflammation in obesity are incompletely understood. Here we show that obesity in mice stimulates hepatocytes to synthesize and secrete dipeptidyl peptidase 4 (DPP4), which acts with plasma factor Xa to inflame ATMs. Silencing expression of DPP4 in hepatocytes suppresses inflammation of VAT and insulin resistance; however, a similar effect is not seen with the orally administered DPP4 inhibitor sitagliptin. Inflammation and insulin resistance are also suppressed by silencing expression of caveolin-1 or PAR2 in ATMs; these proteins mediate the actions of DPP4 and factor Xa, respectively. Thus, hepatocyte DPP4 promotes VAT inflammation and insulin resistance in obesity, and targeting this pathway may have metabolic benefits that are distinct from those observed with oral DPP4 inhibitors.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.