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ERATO
Exploratory Research for Advanced Technology 
戦略的創造研究推進事業(総括実施型研究)
創造科学犠実推進事業
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TORII Nutrient-Stasis
Research Director: Dr.Kunio Torii
(Chief Researcher Physiology and Nutrition Section Life Science Laboratories, Central Research Laboratories, Ajinomoto Co., Inc.)
Research Term 1990-1995
 
Outline of Research Results
 It has long been suspected that animals have the ability to seek out the nutrients necessary for health. Their metabolism is continuously changing so as to maintain an optimal balance among nutrients, a process that gives rise to the project's name, "nutrient-stasis." This project focused on the ability of animals to maintain nutrient stasis for protein.

Research Results

Operant study involving a lysine-deficient diet: In an operant behavioral test, rats fed a L-lysine (Lys)-deficient diet specifically selected a Lys solution. Several days later growth normalized and a preference for monosodium L glutamate (MSG) developed, suggesting that animals under nutrient stress develop a preference for the deficient nutrient.

Localization of the active area in the brain: The direct infusion of Lys into the lateral hypothalamic area of the brain decreased the preference for this nutrient, but did not alter that for other amino acids, thus establishing neuroplasticity in the hypothalamic area. Information may travel from the oblongata to the hypothalamus. The cortex integrates information between the hypothalamus and other areas.

Brain studies by MRI: Functional brain-activity maps by magnetic-resonance imaging (MRI) were generated under Lys deficiency and following the administration of Lys. The results suggest that the lateral hypothalamic area (LHA), and probably the ventro-medial hypothalamus (VMH), are recognition sites for the intake of Lys.

Neurotropic factors in serum: Neurotropic factors were assayed in the serum of rats with and without protein or Lys deficiency. An increase in serum inhibin and activin A was observed in rats fed Lys-sufficient and nonprotein diets, respectively. Under Lys deficiency, serum activin A activity was suppressed. These altered levels of neurotropic factors may elicit plasticity in brain nuclei, which then drive selective ingestive behaviors to alleviate the nutrient deficiency.

Localization of activin A activity: The soma of the LHA and VMH neurons was stained positively for activin A. Results suggest that activin A activity in the brain is likely to be regulated by a concomitant release of inhibin, acting as a competitive inhibitor to activin A's receptor. These two humoral factors may be released under Lys deficiency, and, subsequently, regulate the intake of Lys solution through neuroplasticity, thereby establishing a learned preference.

Localization of Lys and MSG-specific neurons: Experiments have suggested the possibility that LHA neurons have plasticity to specific tastes and help an animal to integrate the taste for a particular substance with physiological need.

graph1

·Neuron response in the brain to a specific nutrient

graph2

·Brain function of a lys-deficient rat revealed by an MRI method
 

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Exploratory Research for Advanced Technology 
戦略的創造研究推進事業(総括実施型研究)
創造科学技術推進事業 ERATO