Journal
CELL METABOLISM
Volume 5, Issue 2, Pages 103-114Publisher
CELL PRESS
DOI: 10.1016/j.cmet.2007.01.001
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Funding
- NIDDK NIH HHS [DK062049] Funding Source: Medline
- NIGMS NIH HHS [GM56957] Funding Source: Medline
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Metabolic adaptation is required to cope with episodes of protein deprivation and malnutrition. GCN2 eIF2 alpha kinase, a sensor of amino acid deficiency, plays a key role in yeast and mammals in modulating amino acid metabolism as part of adaptation to nutrient deprivation. The role of GCN2 in adaptation to long-term amino acid deprivation in mammals, however, is poorly understood. We found that expression of lipogenic genes and the activity of fatty acid synthase (FAS) in the liver are repressed and lipid stores in adipose tissue are mobilized in wildtype mice upon leucine deprivation. In contrast, GCN2-deficient mice developed liver steatosis and exhibited reduced lipid mobilization. Liver steatosis in Gcn2(-/-) mice was found to be caused by unrepressed expression of lipogenic genes, including Srebp-1c and Fas. Thus, our study identifies a novel function of GCN2 in regulating lipid metabolism during leucine deprivation in addition to regulating amino acid metabolism.
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