Myeloid-specific deletion of Zfp36 protects against insulin resistance and fatty liver in diet-induced obese mice
| العنوان: | Myeloid-specific deletion of Zfp36 protects against insulin resistance and fatty liver in diet-induced obese mice |
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| المؤلفون: | Caleb B. Kallen, Jason K. Kim, Robert C. Bauer, Valentina Caracciolo, Jeanette Young, Dae Young Jung, Taekyoon Kim, Hye Lim Noh, Perry J. Blackshear, Yingchun Ni, Stephen J. Flowers, Danielle O'Connell, Ross Summer, Donna M. Gonzales, Scott A. Waldman |
| المصدر: | American Journal of Physiology-Endocrinology and Metabolism. 315:E676-E693 |
| بيانات النشر: | American Physiological Society, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, medicine.medical_specialty, Kupffer Cells, Physiology, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Adipose tissue, 030209 endocrinology & metabolism, Inflammation, Diet, High-Fat, Mice, 03 medical and health sciences, 0302 clinical medicine, Insulin resistance, Tristetraprolin, Physiology (medical), Diabetes mellitus, Internal medicine, Diabetes Mellitus, medicine, Animals, Myeloid Cells, Obesity, RNA, Messenger, Mice, Knockout, Zinc finger, business.industry, Insulin, Fatty liver, Transcription Factor RelA, Organ Size, medicine.disease, I-kappa B Kinase, Fatty Liver, 030104 developmental biology, Endocrinology, Adipose Tissue, Cytokines, Insulin Resistance, medicine.symptom, business, Diet-induced obese, Research Article |
| الوصف: | Obesity is associated with adipose tissue inflammation that contributes to insulin resistance. Zinc finger protein 36 (Zfp36) is an mRNA-binding protein that reduces inflammation by binding to cytokine transcripts and promoting their degradation. We hypothesized that myeloid-specific deficiency of Zfp36 would lead to increased adipose tissue inflammation and reduced insulin sensitivity in diet-induced obese mice. As expected, wild-type (Control) mice became obese and diabetic on a high-fat diet, and obese mice with myeloid-specific loss of Zfp36 [knockout (KO)] demonstrated increased adipose tissue and liver cytokine mRNA expression compared with Control mice. Unexpectedly, in glucose tolerance testing and hyperinsulinemic-euglycemic clamp studies, myeloid Zfp36 KO mice demonstrated improved insulin sensitivity compared with Control mice. Obese KO and Control mice had similar macrophage infiltration of the adipose depots and similar peripheral cytokine levels, but lean and obese KO mice demonstrated increased Kupffer cell (KC; the hepatic macrophage)-expressed Mac2 compared with lean Control mice. Insulin resistance in obese Control mice was associated with enhanced Zfp36 expression in KCs. Compared with Control mice, KO mice demonstrated increased hepatic mRNA expression of a multitude of classical (M1) inflammatory cytokines/chemokines, and this M1-inflammatory hepatic milieu was associated with enhanced nuclear localization of IKKβ and the p65 subunit of NF-κB. Our data confirm the important role of innate immune cells in regulating hepatic insulin sensitivity and lipid metabolism, challenge-prevailing models in which M1 inflammatory responses predict insulin resistance, and indicate that myeloid-expressed Zfp36 modulates the response to insulin in mice. |
| تدمد: | 1522-1555 0193-1849 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b6ee91aa4cfd3735252f95b99d4e7bd5 https://doi.org/10.1152/ajpendo.00224.2017 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....b6ee91aa4cfd3735252f95b99d4e7bd5 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15221555 01931849 |
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