Myeloid SIRT1 regulates macrophage infiltration and insulin sensitivity in mice fed a high-fat diet
| العنوان: | Myeloid SIRT1 regulates macrophage infiltration and insulin sensitivity in mice fed a high-fat diet |
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| المؤلفون: | Eun Ju Bae, Byung-Hyun Park, Mi-Young Song, Sun-O Ka |
| المصدر: | Journal of Endocrinology. 224:109-118 |
| بيانات النشر: | Bioscientifica, 2014. |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Macrophage polarization, Adipose tissue, Inflammation, Biology, Diet, High-Fat, Macrophage chemotaxis, Proinflammatory cytokine, Islets of Langerhans, Mice, Endocrinology, Insulin resistance, Sirtuin 1, Cell Movement, Internal medicine, medicine, Animals, Humans, Macrophage, Myeloid Cells, Cells, Cultured, Cell Migration Assays, Macrophage, Mice, Knockout, Macrophages, Pancreatic islets, medicine.disease, Dietary Fats, HEK293 Cells, medicine.anatomical_structure, Adipose Tissue, Liver, Atrophy, Insulin Resistance, medicine.symptom |
| الوصف: | Inflammation is an important factor in the development of insulin resistance. SIRT1, a class 3 histone/protein deacetylase, has anti-inflammatory functions. Myeloid-specific deletion ofSirt1promotes macrophage infiltration into insulin-sensitive organs and aggravates tissue inflammation. In this study, we investigated how SIRT1 in macrophages alters tissue inflammation in the pancreas as well as liver and adipose tissue, and further explored the role of SIRT1 in locomotion of macrophages. Myeloid-specificSirt1-deleted mice (mS1KO) and WT littermates were fed a 60% calorie high-fat diet (HFD) for 16 weeks. Tissue inflammation and metabolic phenotypes were compared. Bone marrow macrophages (BMMs) from WT or mS1KO mice were used inin vitrochemotaxis assays and macrophage polarization studies. mS1KO mice fed a HFD exhibited glucose intolerance, reduced insulin secretion, and insulin sensitivity with a slight decrease in body weight. Consistent with these results, pancreatic islets of mS1KO mice fed a HFD displayed decreased mass with profound apoptotic cell damage and increased macrophage infiltration and inflammation. Liver and adipose tissues from mS1KO HFD mice also showed greater accumulation of macrophages and tissue inflammation. Results fromin vitroexperiments indicated that deletion of myeloidSirt1stimulated proinflammatory M1-like polarization of BMMs and augmented the adipocyte-mediated macrophage chemotaxis. The latter effect was accompanied by increased expression and acetylation of focal adhesion kinase, as well as nuclear factor kappa B. Our results indicate that myeloid SIRT1 plays a crucial role in macrophage polarization and chemotaxis, and thus regulates the development of HFD-induced pancreatic inflammation and insulin secretion, and metabolic derangements in liver and adipose tissue. |
| تدمد: | 1479-6805 0022-0795 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7f3d3f1da4998b3dd9c761d151d63546Test https://doi.org/10.1530/joe-14-0527Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....7f3d3f1da4998b3dd9c761d151d63546 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14796805 00220795 |
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