| First Author | Yi CX | Year | 2017 |
| Journal | Nat Commun | Volume | 8 |
| Pages | 15143 | PubMed ID | 28489068 |
| Mgi Jnum | J:250358 | Mgi Id | MGI:5920536 |
| Doi | 10.1038/ncomms15143 | Citation | Yi CX, et al. (2017) TNFalpha drives mitochondrial stress in POMC neurons in obesity. Nat Commun 8:15143 |
| abstractText | 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 TNFalpha 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 TNFalpha 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 TNFalpha secretion induces mitochondrial stress in POMC neurons that contributes to the development of obesity. |
