دورية أكاديمية
Loss of Kupffer cells in diet-induced obesity is associated with increased hepatic steatosis, STAT3 signaling, and further decreases in insulin signaling
| العنوان: | Loss of Kupffer cells in diet-induced obesity is associated with increased hepatic steatosis, STAT3 signaling, and further decreases in insulin signaling |
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| المؤلفون: | Clementi, Alicia H., Gaudy, Allison M., Rooijen, Nico Van, Pierce, Robert H., Mooney, Robert A. |
| المساهمون: | Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Department of Pharmacology and Physiology, Department of Molecular Cell Biology, Free University Medical Center Amsterdam, Department of Experimental Pathology & Pharmacology |
| المصدر: | ISSN: 0925-4439 ; Biochimica et Biophysica Acta - Molecular Basis of Disease ; https://hal.archives-ouvertes.fr/hal-00562925Test ; Biochimica et Biophysica Acta - Molecular Basis of Disease, Elsevier, 2009, 1792 (11), pp.1062. ⟨10.1016/j.bbadis.2009.08.007⟩. |
| بيانات النشر: | HAL CCSD Elsevier |
| سنة النشر: | 2009 |
| المجموعة: | Archive ouverte HAL (Hyper Article en Ligne, CCSD - Centre pour la Communication Scientifique Directe) |
| مصطلحات موضوعية: | Kupffer cell, macrophage, diet-induced obesity, inflammation, steatosis |
| الوصف: | International audience ; While adipose tissue-associated macrophages contribute to development of chronic inflammation and insulin resistance of obesity, little is known about the role of hepatic Kupffer cells in this environment. Here we address the impact of Kupffer cell ablation using clodronate-encapsulated liposome depletion in a diet-induced obese (DIO) and insulin resistant mouse model. Hepatic expression of macrophage markers measured by realtime RT-PCR remained unaltered in DIO mice despite characteristic expansion of adipose tissue-associated macrophages. DIO mouse livers displayed increased expression of alternative activation markers but unaltered proinflammatory cytokine expression when compared to lean mice. Kupffer cell ablation reduced hepatic anti-inflammatory cytokine IL-10 mRNA expression in lean and DIO mice by 95% and 84%, respectively. Despite decreased hepatic IL-6 gene expression after ablation in lean and DIO mice, hepatic STAT3 phosphorylation, and acute phase protein mRNA expression increased. Kupffer cell ablation in DIO mice resulted in additional hepatic triglyceride accumulation and a 30-40% reduction in hepatic insulin receptor autophosphorylation and Akt activation. Implicating systemic loss of IL-10, high-fat-fed IL-10 knockout mice also displayed increased hepatic STAT3 signaling and hepatic triglyceride accumulation. Insulin signaling was not altered, however. In conclusion, Kupffer cells are a major source of hepatic IL-10 expression, the loss of which is associated with increased STAT3-dependent signaling and steatosis. One or more additional factors appear to be required, however, for the Kupffer cell-dependent protective effect on insulin receptor signaling in DIO mice. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | hal-00562925; https://hal.archives-ouvertes.fr/hal-00562925Test; https://hal.archives-ouvertes.fr/hal-00562925/documentTest; https://hal.archives-ouvertes.fr/hal-00562925/file/PEER_stage2_10.1016%252Fj.bbadis.2009.08.007.pdfTest |
| DOI: | 10.1016/j.bbadis.2009.08.007 |
| الإتاحة: | https://doi.org/10.1016/j.bbadis.2009.08.007Test https://hal.archives-ouvertes.fr/hal-00562925Test https://hal.archives-ouvertes.fr/hal-00562925/documentTest https://hal.archives-ouvertes.fr/hal-00562925/file/PEER_stage2_10.1016%252Fj.bbadis.2009.08.007.pdfTest |
| حقوق: | info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: | edsbas.EA06F195 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1016/j.bbadis.2009.08.007 |
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