| Co-Investigator(Kenkyū-buntansha) |
KIMURA Akinori KYUSYU UNIVERSITY FACULTY OF MEDICINE ASSOCIATE PROFESSOR, 医学部, 助教授 (60161551)
YOSHIMATSU Hironobu OITA MEDICAL UNIVERSITY, FACULTY OF MEDICINE ASSISTANT PROFESSOR, 医学部, 助手 (00166993)
SATO Yasufumi OITA MEDICAL UNIVERSITY, FACULTY OF MEDICINE ASSISTANT PROFESSOR, 医学部, 助手 (50178779)
KOHNO Kimitoshi OITA MEDICAL UNIVERSITY, FACULTY OF MEDICINE ASSOCIATE PROFESSOR, 医学部, 助教授 (00153479)
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| Research Abstract |
Genetically obese Zucker rats have been shown to have abnormalities in regulation of adaptive behavior, body temperature and metabolism. Present study aims to clarify whether impairment of histaminergic system in the hypothalamus may cause these regulatory dysfunctions.
Results : 1) Obese Zuckers had defect in behavioral responses to manipulation of gypothalamic neuronal histamine. 2) Concentration of neuronal histamine was hardly detectable in the obese Zucker hypothalamus. The defect in neuronal histamine of the obese Zuckers was resulted from inactivity of histamine synthesizing enzyme, histidine decarboxylase (HDC), compared to that of lean littermates and wistar King A rats. 3)Obese rats showed abnormal feeding behavior including dysruption of circadian rhythm, increase in size and duration of a meal, decrease in eating speed, and dysfunction of mastication.
The abnormalities mimiced those of the Wistar King A rats, from which neuronal histamine was depleted by use of alpha-fluorome
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thylhistidine (FMH), a suicide inhibitor of HDC.4)Energy deficiency due to starvation, insulin-induced hypoglycemia, and intracellular glucoprivation induced by 2-deoxy-D-glucose activated histaminergic system in the hypothalamus. 5) The activation of histaminergic system induced glycogenolysis in the hypothalamus, which resulted in homeostatic maintenance of energy supply. 6)Obese Zuckers failed to regulate energy metabolism under glucoprivic condition controled by histaminergic system. 7)Both obese Zuckers and histamine-depleted rats showed distorted adaptive behavior for high ambient temperature. 7)Abnormalitiy of HDC gene could not be demonstrated by molecular biology, but its genetic rearrangement such as point mutation was highly probable.
These results indicate that dysfunction of histaminergic system in the hypothalamus may cause abnormalities of Zucker obese rats, because hypothalamic neuronal histamine has been found to be crucial for integration of homeostatic energy metabolism. Less
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