Transcriptional regulation of energy metabolism in metabolic syndrome.
| Project/Area Number |
18390268
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Metabolomics
|
|---|
| Research Institution | University of Tsukuba |
|---|
Principal Investigator |
YAMADA Nobuhiro University of Tsukuba, GraduateSchool of Comprehensive Human Sciences, Professor (40200729)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
SHIMANO Hitoshi University of Tsukuba, Graduate School of Comprehensive Human Sciences, Professor (20251241)
TAKAHASHI Akimitsu University of Tsukuba, Graduate School of Comprehensive Human Sciences, Assistant Professor (70344893)
豊島 秀男 筑波大学, 大学院人間総合科学研究科, 講師 (20197966)
|
|---|
| Project Period (FY) |
2006 – 2007
|
| Project Status |
Completed (Fiscal Year 2007)
|
| Budget Amount *help |
¥17,460,000 (Direct Cost: ¥15,600,000、Indirect Cost: ¥1,860,000)
Fiscal Year 2007: ¥8,060,000 (Direct Cost: ¥6,200,000、Indirect Cost: ¥1,860,000)
Fiscal Year 2006: ¥9,400,000 (Direct Cost: ¥9,400,000)
|
|---|
| Keywords | metabolic syndrome / insulin resistance / transcription factor / energy metabolism / diabetes mellitus |
|---|
| Research Abstract |
Insulin resistance is often associated with obesity and can precipitate type 2 diabetes. To date, most known approaches that improve insulin resistance must be preceded by the amelioration of obesity and hepatosteatosis. Here, we show that this provision is not mandatory; insulin resistance and hyperglycemia are improved by the modification of hepatic fatty acid composition, even in the presence of persistent obesity and hepatosteatosis. Mice deficient for Elov 16, the gene encoding the elongase that catalyzes the conversion of palmitate to stearate, were generated and shown to become obese and develop hepatosteatosis when fed a high-fat diet or mated to leptin-deficient ob/ob mice. However, they showed marked protection from hyperinsulinemia, hyperglycemia and hyperleptinemia. Amelioration of insulin resistance was associated with restoration of hepatic insulin receptor substrate-2 and suppression of hepatic protein kinase C e activity resulting in restoration of Akt phosphorylation. Collectively, these data show that hepatic fatty acid composition is a new determinant for insulin sensitivity that acts independently of cellular energy balance and stress. Inhibition of this elongase could be a new therapeutic approach for ameliorating insulin resistance, diabetes and cardiovascular risks, even in the presence of a continuing state of obesity.
|
Report
(3 results)
Research Products
(33 results)
