ArticleAmerican journal of physiology. Endocrinology and metabolism2013
CD40 deficiency in mice exacerbates obesity-induced adipose tissue inflammation, hepatic steatosis, and insulin resistance.
Article in American journal of physiology. Endocrinology and metabolism, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 52 citations in OpenAlex.
- Association between targeted inflammatory proteomics and insulin sensitivity as well as beta-cell function in subjects with normal glucose tolerance.Journal of molecular cell biology · 2026Article
- The bidirectional immune crosstalk in metabolic dysfunction-associated steatotic liver disease.Cell metabolism · 2023Review
- Adipocytes control hematopoiesis and inflammation through CD40 signaling.Haematologica · 2023Article
- Identification of potential hub genes linked to immune and metabolic alterations in postoperative systemic inflammatory dysregulation.Frontiers in immunology · 2023Article
- Downregulation of sCD40 and sCTLA4 in Recovered COVID-19 Patients with Comorbidities.Pathogens (Basel, Switzerland) · 2022Article
- Progress and Prospects of Non-Canonical NF-κB Signaling Pathway in the Regulation of Liver Diseases.Molecules (Basel, Switzerland) · 2022Review
- Multiomics Analysis Reveals the Impact of Microbiota on Host Metabolism in Hepatic Steatosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- CD47 differentially regulates white and brown fat function.Biology open · 2020Article
- Comparative Transcriptomic Analysis of Subcutaneous Adipose Tissue from Local Pig Breeds.Genes · 2020Article
- Depletion of CD40 on CD11cScientific reports · 2019Article
- Inflammation and Immunity: From an Adipocyte's Perspective.Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research · 2019Review
- Silencing an insulin-induced lncRNA, LncASIR, impairs the transcriptional response to insulin signalling in adipocytes.Scientific reports · 2019Article
- Deficiency of T cell CD40L has minor beneficial effects on obesity-induced metabolic dysfunction.BMJ open diabetes research & care · 2019Article
- Article
- JAZF1 Inhibits Adipose Tissue Macrophages and Adipose Tissue Inflammation in Diet-Induced Diabetic Mice.BioMed research international · 2018Article
- Heterozygosity for the rs696217 SNP in the Preproghrelin Gene Predicts Weight Loss After Bariatric Surgery in Severely Obese Individuals.Obesity surgery · 2017Article
- CD40 promotes MHC class II expression on adipose tissue macrophages and regulates adipose tissue CD4+ T cells with obesity.Journal of leukocyte biology · 2016Article
- The Immune Landscape in Nonalcoholic Steatohepatitis.Immune network · 2016Review
- AHNAK deficiency promotes browning and lipolysis in mice via increased responsiveness to β-adrenergic signalling.Scientific reports · 2016Article
- The role of immune cells in metabolism-related liver inflammation and development of non-alcoholic steatohepatitis (NASH).Reviews in endocrine & metabolic disorders · 2016Review
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
The pathophysiology of obesity and type 2 diabetes in rodents and humans is characterized by low-grade inflammation in adipose tissue and liver. The CD40 receptor and its ligand CD40L initiate immune cell signaling promoting inflammation, but conflicting data on CD40L-null mice confound its role in obesity-associated insulin resistance. Here, we demonstrate that CD40 receptor-deficient mice on a high-fat diet display the expected decrease in hepatic cytokine levels but paradoxically exhibit liver steatosis, insulin resistance, and glucose intolerance compared with their age-matched wild-type controls. Hyperinsulinemic-euglycemic clamp studies also demonstrated insulin resistance in glucose utilization by the CD40-null mice compared with wild-type mice. In contrast to liver, adipose tissue in CD40-deficient animals harbors elevated cytokine levels and infiltration of inflammatory cells, particularly macrophages and CD8(+) effector T cells. In addition, ex vivo explants of epididymal adipose tissue from CD40(-/-) mice display elevated basal and isoproterenol-stimulated lipolysis, suggesting a potential increase of lipid efflux from visceral fat to the liver. These findings reveal that 1) CD40-null mice represent an unusual model of hepatic steatosis with reduced hepatic inflammation, and 2) CD40 unexpectedly functions in adipose tissue to attenuate its inflammation in obesity, thereby protecting against hepatic steatosis.
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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.