| Autor: |
Ou, Zhimin, Ma, Yanchen, Sun, Yuxia, Zheng, Gege, Wang, Shiyun, Xing, Rui, Chen, Xiang, Han, Ying, Wang, Jiajia, Lu, Q. Richard, Zhao, Tong-Jin, Chen, Ying |
| Zdroj: |
Cell Reports; Mar2019, Vol. 26 Issue 11, p2984-2984, 1p |
| Abstrakt: |
The CNS plays a pivotal role in energy homeostasis, but whether oligodendrocytes are involved has been largely unexplored. Here, we show that signaling through GPR17, a G-protein-coupled receptor predominantly expressed in the oligodendrocyte lineage, regulates food intake by modulating hypothalamic neuronal activities. GPR17 -null mice and mice with an oligodendrocyte-specific knockout of GPR17 have lean phenotypes on a high-fat diet, suggesting that GPR17 regulates body weight by way of oligodendrocytes. Downregulation of GPR17 results in activation of cAMP-protein kinase A (PKA) signaling in oligodendrocytes and upregulated expression of pyruvate dehydrogenase kinase 1 (PDK1), which promotes lactate production. Elevation of lactate activates AKT and STAT3 signaling in the hypothalamic neurons, leading to increased expression of Pomc and suppression of Agrp. Our findings uncover a critical role of oligodendrocytes in metabolic homeostasis, where GPR17 modulates the production of lactate, which, in turn, acts as a metabolic signal to regulate neuronal activity. • GPR17-deficient mice are resistant to high-fat-diet-induced obesity • Oligodendrocytic Gpr17 signaling controls metabolic homeostasis and food intake • Oligodendrocyte lactate is a metabolic signal for neuronal AKT/STAT3 signaling • Oligodendrocytic GPR17-cAMP-lactate axis regulates neuronal activity Ou et. al. show that Gpr17 in oligodendrocytes contributes to whole-body metabolic regulation. Gpr17 -deficient mice exhibit decreased body weight on long-term high-fat feeding by reducing food intake. Loss of Gpr17 increases oligodendrocytic lactate production, which results in the lean phenotype of the KO animals. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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