Myeloid Krüppel-like factor 2 is a critical regulator of metabolic inflammation
| Autor: | Nikunj Sharma, David R Sweet, Panjamaporn Sangwung, Yoichi Takami, Neelakantan T Vasudevan, Anthony Wynshaw-Boris, Paul Holvoet, Yuan Lu, Liyan Fan, Xudong Liao, Stanton L. Gerson, E. Ricky Chan, Chen Fu, Chloe E Booth, Vinesh Vinayachandran, Guangjin Zhou, Lilei Zhang, Keiichiro Matoba, Yulan Qing, Komal S Keerthy, Mukesh K. Jain, Lalitha Nayak, Derin Tugal |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Central Nervous System Male Myeloid Regulator General Physics and Astronomy Eating Mice 0302 clinical medicine Myeloid Cells lcsh:Science Mice Knockout INSULIN-RESISTANCE Multidisciplinary KLF2 Type 2 diabetes Metabolic syndrome Multidisciplinary Sciences medicine.anatomical_structure OBESITY Knockout mouse Science & Technology - Other Topics medicine.symptom EXPRESSION Science Kruppel-Like Transcription Factors Inflammation Diet High-Fat General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences Insulin resistance Immune system Metabolic Diseases Peripheral Nervous System medicine Animals Humans Obesity Science & Technology business.industry General Chemistry medicine.disease 030104 developmental biology Cancer research lcsh:Q JNK Insulin Resistance business 030217 neurology & neurosurgery Microglial cells |
| Zdroj: | Nature Communications, Vol 11, Iss 1, Pp 1-11 (2020) Nature Communications |
| ISSN: | 2041-1723 |
| Popis: | Substantial evidence implicates crosstalk between metabolic tissues and the immune system in the inception and progression of obesity. However, molecular regulators that orchestrate metaflammation both centrally and peripherally remains incompletely understood. Here, we identify myeloid Krüppel-like factor 2 (KLF2) as an essential regulator of obesity and its sequelae. In mice and humans, consumption of a fatty diet downregulates myeloid KLF2 levels. Under basal conditions, myeloid-specific KLF2 knockout mice (K2KO) exhibit increased feeding and weight gain. High-fat diet (HFD) feeding further exacerbates the K2KO metabolic disease phenotype. Mechanistically, loss of myeloid KLF2 increases metaflammation in peripheral and central tissues. A combination of pair-feeding, bone marrow-transplant, and microglial ablation implicate central and peripheral contributions to K2KO-induced metabolic dysfunction observed. Finally, overexpression of myeloid KLF2 protects mice from HFD-induced obesity and insulin resistance. Together, these data establish myeloid KLF2 as a nodal regulator of central and peripheral metabolic inflammation in homeostasis and disease. Inflammation contributes to the development of metabolic disease through incompletely understood mechanisms. Here the authors report that deletion of the transcription factor KLF2 in myeloid cells leads to increased feeding and weight gain in mice with concomitant peripheral and central tissue inflammation, while overexpression protects against diet-induced metabolic disease. |
| Databáze: | OpenAIRE |
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