Regulation of Fat Metabilism Induced by Amino Acid Deprivation

Project: Research project

Project Details

Description

Project Summary
Malnutrition and nutrient deprivation are the single largest contributors to human
mortality and profoundly impacts the severity and susceptibility to diseases. Amino acid
and protein deprivation is the most common form of malnutrition in humans. We
discovered that deprivation of essential amino acids has a profound impact on fat
metabolism by repressing fat synthesis in the liver and inducing the loss of adipose tissue
resulting in the complete depletion visceral fat stores. The response to deprivation of the
essential amino acid leucine mimics a starvation response and is regulated by the amino
acid sensor GCN2 eIF2 alpha kinase. More recently we discovered that GCN2 is required
to repress both lipogenic and cholesterogenic gene expression during fasting. We propose
to investigate the mechanism of whereby GCN2 represses the expression of the SREBPs,
the key regulators of hepatic lipogenesis and cholesterogenesis. Studies to compare
adaptation to fasting and deprivation of single essential amino acids in the liver will be
conducted to determine shared and divergent regulatory pathways. In parallel, the
regulation of loss of visceral fat, induced by depletion of essential amino acids, will be
investigated to determine the role of GCN2 in controlling the oxidation of fatty acids
during nutrient deprivation.
StatusFinished
Effective start/end date8/1/087/31/10

Funding

  • National Institute of General Medical Sciences: $291,034.00

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