2001 Fiscal Year Final Research Report Summary
Treatment of obesity and diabetes by the neuronal factor
| Project/Area Number |
10470233
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Metabolomics
|
|---|
| Research Institution | OITA MEDICAL UNIVERSITY |
|---|
Principal Investigator |
SAKATA Toshiie Oita medical university, school of medicine, Professor, 医学部, 教授 (50037420)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
YOSHIMATSU Hironobu Oita medical university, school of medicine, Associate Professor, 医学部, 助教授 (00166993)
|
|---|
| Project Period (FY) |
1998 – 2000
|
| Keywords | Energy homeostasis / Uncoupling protein / Neuronal histamine / Leptin / Diabetes |
|---|
| Research Abstract |
We analyze energy homOastasis including uncoupling protein (UCF) family mRNA expression in diabetic state. UCP1 mRNA expression in brown adipose tissue (BAT) was decreased in storeptozocin (STZ)-induced diabetes rat compared with control rats. UCP2 mRNA in BAT, white adipose tissue (WAT), and skeletal muscle (MSL) were increased in STZ diabetic rat. In contrast, UCP3 mRNA, not UCP2 mRNA, was increased in heart concomitantly increase with free fatty acid (EFA). However, heart UCP3 mRNA was not increased in zucker fatty obese rats which shown chromic hyper free fatty acidemia. These results indicated that UCP family mRNA expressions were tissue-dependently regulated in diabetic state and heart UCP3 mRNA was regulated FFA in acute phase. We next analyze energy homeostasis regulated by neuronal histamine. Visceral adiposity and ob mRNA expression in WAT were increased in histamine H_1, receptor (H_1R) knockout (H1KO) mice. In addition, the effects of leptin on food intake and BAT UCP1 mRNA expression were attenuated in H1KO mice. Furthermore, central administration of histamine decreased daily food intake and BAT UCP1 mRNA expression even in leptin resistant db/db obese mice. These studies demonstrated that neuronal histamine including H_1 -R is the target of leptin in food intake, adiposity, BAT UCP1 mRNA expression and neuronal histamine can act energy homeostasis during leptin resistant obesity.
|
