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DOI | 10.1038/s41467-018-05042-6 |
TNF alpha drives mitochondrial stress in POMC neurons in obesity | |
Yi, Chun-Xia1,2; Walter, Marc1; Gao, Yuanqing1; Pitra, Soledad3; Legutko, Beata1; Kaelin, Stefanie1; Layritz, Clarita1; Garcia-Caceres, Cristina1; Bielohuby, Maximilian4; Bidlingmaier, Martin4; Woods, Stephen C.5; Ghanem, Alexander6,7; Conzelmann, Karl-Klaus6,7; Stern, Javier E.3; Jastroch, Martin1; Tschoep, Matthias H.1 | |
2017-05-10 | |
发表期刊 | NATURE COMMUNICATIONS
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ISSN | 2041-1723 |
出版年 | 2017 |
卷号 | 8 |
文章类型 | Article |
语种 | 英语 |
国家 | Germany; Netherlands; USA |
英文摘要 | Consuming a calorically dense diet stimulates microglial reactivity in the mediobasal hypothalamus (MBH) in association with decreased number of appetite-curbing pro-opiomelanocortin (POMC) neurons; whether the reduction in POMC neuronal function is secondary to the microglial activation is unclear. Here we show that in hypercaloric diet-induced obese mice, persistently activated microglia in the MBH hypersecrete TNF alpha that in turn stimulate mitochondrial ATP production in POMC neurons, promoting mitochondrial fusion in their neurites, and increasing POMC neuronal firing rates and excitability. Specific disruption of the gene expressions of TNF alpha downstream signals TNFSF11A or NDUFAB1 in the MBH of diet-induced obese mice reverses mitochondrial elongation and reduces obesity. These data imply that in a hypercaloric environment, persistent elevation of microglial reactivity and consequent TNF alpha secretion induces mitochondrial stress in POMC neurons that contributes to the development of obesity. |
领域 | 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000400887100001 |
WOS关键词 | KAPPA-B ; NEURODEGENERATIVE DISEASES ; CELL-SURVIVAL ; INFLAMMATION ; SICKNESS ; DYNAMICS ; MEDIATE ; CORTEX ; DIET |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/203866 |
专题 | 资源环境科学 |
作者单位 | 1.Tech Univ Munich, German Ctr Diabet Res DZD, Helmholtz Zentrum Munchen,Dept Med, Inst Diabet & Obes,Helmholtz Diabet Ctr,Div Metab, D-85764 Munich, Germany; 2.Univ Amsterdam, Acad Med Ctr, Dept Endocrinol & Metab, NL-1105 AZ Amsterdam, Netherlands; 3.Augusta Univ, Dept Physiol, Augusta, GA 30912 USA; 4.Klinikum Ludwig Maximilians Univ, Endocrine Res Unit, D-81377 Munich, Germany; 5.Univ Cincinnati, Dept Psychiat & Behav Neurosci, Cincinnati, OH 45220 USA; 6.Ludwig Maximilians Univ Munchen, Max von Pettenkofer Inst, D-80539 Munich, Germany; 7.Ludwig Maximilians Univ Munchen, Gene Ctr, D-80539 Munich, Germany |
推荐引用方式 GB/T 7714 | Yi, Chun-Xia,Walter, Marc,Gao, Yuanqing,et al. TNF alpha drives mitochondrial stress in POMC neurons in obesity[J]. NATURE COMMUNICATIONS,2017,8. |
APA | Yi, Chun-Xia.,Walter, Marc.,Gao, Yuanqing.,Pitra, Soledad.,Legutko, Beata.,...&Tschoep, Matthias H..(2017).TNF alpha drives mitochondrial stress in POMC neurons in obesity.NATURE COMMUNICATIONS,8. |
MLA | Yi, Chun-Xia,et al."TNF alpha drives mitochondrial stress in POMC neurons in obesity".NATURE COMMUNICATIONS 8(2017). |
条目包含的文件 | 条目无相关文件。 |
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