Activation of GCN2/ATF4 signals in amygdalar PKC-δ neurons promotes WAT browning under leucine deprivation

Feixiang Yuan, Haizhou Jiang, Hanrui Yin, Xiaoxue Jiang, Fuxin Jiao, Shanghai Chen, Hao Ying, Yan Chen, Qiwei Zhai and Feifan Guo ()
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Feixiang Yuan: University of Chinese Academy of Sciences, Chinese Academy of Sciences
Haizhou Jiang: University of Chinese Academy of Sciences, Chinese Academy of Sciences
Hanrui Yin: University of Chinese Academy of Sciences, Chinese Academy of Sciences
Xiaoxue Jiang: University of Chinese Academy of Sciences, Chinese Academy of Sciences
Fuxin Jiao: University of Chinese Academy of Sciences, Chinese Academy of Sciences
Shanghai Chen: University of Chinese Academy of Sciences, Chinese Academy of Sciences
Hao Ying: University of Chinese Academy of Sciences, Chinese Academy of Sciences
Yan Chen: University of Chinese Academy of Sciences, Chinese Academy of Sciences
Qiwei Zhai: University of Chinese Academy of Sciences, Chinese Academy of Sciences
Feifan Guo: University of Chinese Academy of Sciences, Chinese Academy of Sciences

Nature Communications, 2020, vol. 11, issue 1, 1-12

Abstract: Abstract The browning of white adipose tissue (WAT) has got much attention for its potential beneficial effects on metabolic disorders, however, the nutritional factors and neuronal signals involved remain largely unknown. We sought to investigate whether WAT browning is stimulated by leucine deprivation, and whether the amino acid sensor, general control non-derepressible 2 (GCN2), in amygdalar protein kinase C-δ (PKC-δ) neurons contributes to this regulation. Our results show that leucine deficiency can induce WAT browning, which is unlikely to be caused by food intake, but is largely blocked by PKC-δ neuronal inhibition and amygdalar GCN2 deletion. Furthermore, GCN2 knockdown in amygdalar PKC-δ neurons blocks WAT browning, which is reversed by over-expression of amino acid responsive gene activating transcription factor 4 (ATF4), and is mediated by the activities of amygdalar PKC-δ neurons and the sympathetic nervous system. Our data demonstrate that GCN2/ATF4 can regulate WAT browning in amygdalar PKC-δ neurons under leucine deprivation.

Date: 2020
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DOI: 10.1038/s41467-020-16662-2

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