| Project/Area Number |
10670066
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Environmental physiology (including Physical medicine and Nutritional physiology)
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| Research Institution | OITA MEDICAL UNIVERSITY |
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Principal Investigator |
YOSIMATSU Hironobu DEPARTMENT OF INTERNAL MEDICINE I, SCHOOL OF MEDICINE, OOITA MEDICAL UNIVERSITY, 医学部, 助教授 (00166993)
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| Co-Investigator(Kenkyū-buntansha) |
SAKATA Toshiie DEPARTMENT OF INTERNAL MEDICINE I, SCHOOL OF MEDICINE, OOITA MEDICAL UNIVERSITY, 医学部, 教授 (50037420)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1999: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1998: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | leptin resistance / hypothalamus / fatty acid / diet-induced obesity / Zucker fa / fa rat / OLETF rat / neuronal histamine / agouti mice / レプチン / 肥満症 / Zucker fatty rat / Zucker obese rat |
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| Research Abstract |
We aimed to clarify the involvement of fatty acids in the development of leptin resistance during the progression of obesity. In the liver of diet induced obese (DIO) rats using 34% sucrose loading, an increase in palmitolenic acid and oleinic acid as mono unsaturated fatty acids (MUFA) and a decrease in linoleic acid and arachidonic acid as poly unsaturated fatty acids (PUFA) were observed after 4 weeks as well as 20 weeks sucrose loading. These chnges in fatty acids component in other tissue including the white adipose tissue (WAT) and the muscle were detected only in 20 weeks sucrose loading rats which showed remarkable obesity. These results indicate that the liver is the principal site for the development and the spread of fatty acids imbalance in other target organs, which may induce obesity-related metabolic disturbance such as hyperlipidemia, hypeglycemia and rinsulin resistance. In Zucker fa/fa rats and OLETF rats, models of genetic obesity, the similar changes in fatty acids
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component were observed. In Zucker fa/+ rats, however, content of triglyceride was increased in the liver although hyperphagia and imbalance of fatty acids in the liver were not observed. This result indicates that even partial insufficiency of leptin action can affect liver lipid metabolism without changes in fatty acids component. And it also suggests that fatty acids imbalance observed in obese animals including DIO and genetic obese rats may be cause by nutritional or metabolic factors not by leptin action or leptin resistance. Central nervous system showed characteristic pattern of fatty acids component. Content of linoleic acid significantly decreased in the hypothalamus and the cortex compared with the peripheral tissue. Furthermore, there was no difference in fatty acids component in the hypothalamus between Zucker fa/fa rats and their lean littermates indicating fatty acids balance in the brain was not influenced by peripheral fatty acids metabolism. Loading of high oleinic acid or linoleinic acid containing diet did not affect content of histamine and tele-methylhistamine (tMH), a major metabolite of histamine, in the hypothalamus. No remarkable changes in histamine and tMH content in the hypothalamus were observed in OLETF rats and agouti obese yellow mice, another model of genetic obesity. Loading of sucrose plus high oleinic acid containing diet induced an increase in body weight and fat accumulation compared with sucrose loading only or sucrose plus high lenoleinic acid containing diet. The degree of hyperleptinemia as well as hyperinsulinemia were more prominent in oleinic acid loading animals compared with other DIO animals. These results indicate that oleinic acid promotes fat deposition which induces obesity-related metabolic disorder. In conclusion, oleinic acids may not directly affect leptin signaling in the hypothalamus, rather, it is highly probable that oleinic acid is involved in the development of leptin resistance through affecting peripheral leptin action or transportation of leptin into the brain. Less
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