TNFα drives mitochondrial stress in POMC neurons in obesity

Chun Xia Yi, Marc Walter, Yuanqing Gao, Soledad Pitra, Beata Legutko, Stefanie Kälin, Clarita Layritz, Cristina García-Cáceres, Maximilian Bielohuby, Martin Bidlingmaier, Stephen C. Woods, Alexander Ghanem, Karl Klaus Conzelmann, Javier Eduardo Stern, Martin Jastroch, Matthias H. Tschöp

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

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 TNFα 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 TNFα 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 TNFα secretion induces mitochondrial stress in POMC neurons that contributes to the development of obesity.

Original languageEnglish (US)
Article number15143
JournalNature communications
Volume8
DOIs
StatePublished - 2017

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Fingerprint Dive into the research topics of 'TNFα drives mitochondrial stress in POMC neurons in obesity'. Together they form a unique fingerprint.

  • Cite this

    Yi, C. X., Walter, M., Gao, Y., Pitra, S., Legutko, B., Kälin, S., Layritz, C., García-Cáceres, C., Bielohuby, M., Bidlingmaier, M., Woods, S. C., Ghanem, A., Conzelmann, K. K., Stern, J. E., Jastroch, M., & Tschöp, M. H. (2017). TNFα drives mitochondrial stress in POMC neurons in obesity. Nature communications, 8, [15143]. https://doi.org/10.1038/ncomms15143