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

• DOI: 10.1038/s41467-020-16662-2
• Publication Date: 2020-06-05T10:04:22Z
• Authors: Feixiang Yuan; Haizhou Jiang; Hanrui Yin; Xiaoxue Jiang; Fuxin Jiao; Shanghai Chen; Hao Ying; Yan Chen; Qiwei Zhai; Feifan Guo
• Keywords: Male; Mice, Knockout; Neurons; 0303 health sciences; Sympathetic Nervous System; Science; Adipose Tissue, White; Lipolysis; Q; Thermogenesis; Protein Serine-Threonine Kinases; Amygdala; Activating Transcription Factor 4; Article; Stereotaxic Techniques; Mice; Protein Kinase C-delta; 03 medical and health sciences; Adipose Tissue, Brown; Leucine; Gene Knockdown Techniques; Animals; Signal Transduction

AbstractThe 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.