Molecular mechanisms in the brain involved in the anorexia of branched-chain amino acid deficiency.
The anterior piriform cortex (APC) of the rat is thought to be the site of indispensable amino acid (IAA) chemosensation in the brain. The branched-chain amino acids, including leucine, are among the IAA that are recognized in the APC. The behavioral outcome of IAA deficiency is an anorectic response. The specific transduction mechanisms by which IAA deficiency and repletion activate the APC are not fully understood, but clearly phosphorylation of proteins, increases in intracellular calcium, and expression of the immediate early gene c-fos, which are among the earliest events occurring after the initial drop in the concentration of the limiting IAA, cause stimulation in the APC. Subsequently, several neurotransmitter systems, including those for norepinephrine, GABA, serotonin, dopamine and nitric oxide, are activated in the APC of rats that have consumed an IAA-imbalanced diet. These systems appear to modulate the output cells from the APC, glutamatergic pyramidal cells that send neural signals to activate subsequent relays in the brain. Ultimately, the feeding circuits of the brain carry out the anorectic response. Continued consumption of a diet containing an IAA imbalance causes a conditioned taste aversion to the diet in all animals that have been studied. Such learning involves synaptic reorganization, requiring both degradation and synthesis of protein, along with alterations in genomic activity.
Department of Anatomy, Physiology and Cell Biology, School of Veterinary Medicine and Food Intake Laboratory, University of California-Davis, Davis, CA 95616, USA. dwgietzen@ucdavis.edu
D W
DW
Gietzen
L J
LJ
Magrum
D000597:Amino Acids, Branched-Chain / Q000097:blood / Q000172:deficiency* / Q000378:metabolism*; D000818:Animals; D000855:Anorexia / Q000503:physiopathology*; D001921:Brain / Q000378:metabolism / Q000503:physiopathology*; D002118:Calcium / Q000378:metabolism; D004032:Diet; D005508:Food Deprivation; D015870:Gene Expression; D016762:Genes, fos; D009434:Neural Pathways / Q000503:physiopathology; D018377:Neurotransmitter Agents / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats; D015398:Signal Transduction; D013649:Taste
D000597:Amino Acids, Branched-Chain; D018377:Neurotransmitter Agents; D002118:Calcium