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Curr Opin Clin Nutr Metab Care. 2013 Jan;16(1):96-101. doi: 10.1097/MCO.0b013e32835b618b.

Detection of amino acid deprivation in the central nervous system.

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  • 1Department of Nutritional Sciences, Rutgers, The State University of New Jersey, New Brunswick, New Jersey 08901, USA.



To understand the principles of amino acid deprivation sensing in the brain and its behavioral and metabolic outcomes with an emphasis on the current literature.


Sensing essential amino acid (EAA) depletion occurs in the anterior piriform cortex (APC) via general control nonderepressible 2 (GCN2) binding to deacylated tRNA and subsequent glutamatergic signaling to influence behavior. Mapping of the APC output during EAA insufficiency shows axons projecting to the hypothalamus as well as other regions that are involved in feeding and locomotion. Whereas these neurocircuits are clearly important in regulating anorectic responses to an EAA-devoid diet, the propagating events and regulatory factors are still unclear. Recently, several groups examined signaling and gene expression in the arcuate nucleus and lateral hypothalamus during EAA deficiency. In these efforts, several gene products, including somatostatin, corticotrophin-releasing hormone, neuropeptide Y, agouti-related protein, and several novel targets were identified as factors involved in regulating the aversion to EAA-deficient diets. On a different note, marginal EAA deficiency in the form of methionine restriction promotes hyperphagia similar to low-protein diets, yet animals are leaner and live longer. The central mechanisms are unclear but involve sympathetic nervous signaling. How and why different degrees of EAA deficiency cause opposite changes in behavior and body composition require further study.


Scientific inquiry into the central mechanism by which EAA insufficiency is sensed has identified the APC as the brain's initial EAA chemosensor. Beyond this, much remains uncertain. Future investigation into the signaling and gene expression events occurring in the hypothalamus and other brain regions is warranted.

[PubMed - indexed for MEDLINE]
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