S6K1 in the central nervous system regulates energy expenditure via MC4R/CRH pathways in response to deprivation of an essential amino acid.
It is well established that the central nervous system (CNS), especially the hypothalamus, plays an important role in regulating energy homeostasis and lipid metabolism. We have previously shown that hypothalamic corticotropin-releasing hormone (CRH) is critical for stimulating fat loss in response to dietary leucine deprivation. The molecular mechanisms underlying the CNS regulation of leucine deprivation-stimulated fat loss are, however, still largely unknown. Here, we used intracerebroventricular injection of adenoviral vectors to identify a novel role for hypothalamic p70 S6 kinase 1 (S6K1), a major downstream effector of the kinase mammalian target of rapamycin, in leucine deprivation stimulation of energy expenditure. Furthermore, we show that the effect of hypothalamic S6K1 is mediated by modulation of Crh expression in a melanocortin-4 receptor-dependent manner. Taken together, our studies provide a new perspective for understanding the regulation of energy expenditure by the CNS and the importance of cross-talk between nutritional control and regulation of endocrine signals.
Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai, China.
Tingting
T
Xia
Ying
Y
Cheng
Qian
Q
Zhang
Fei
F
Xiao
Bin
B
Liu
Shanghai
S
Chen
Feifan
F
Guo
D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism*; D004734:Energy Metabolism / Q000502:physiology*; D007031:Hypothalamus / Q000378:metabolism*; D007930:Leucine / Q000172:deficiency*; D008099:Liver; D010766:Phosphorylation; D044105:Receptor, Melanocortin, Type 4 / Q000378:metabolism*; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
D044105:Receptor, Melanocortin, Type 4; D003346:Corticotropin-Releasing Hormone; D038744:Ribosomal Protein S6 Kinases, 90-kDa; C512964:Rps6ka1 protein, mouse; D007930:Leucine