| Budget Amount *help |
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2020: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2019: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2018: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
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| Outline of Final Research Achievements |
ELOVL fatty acid elongase 6 (Elovl6) is responsible for converting C16 saturated and monounsaturated fatty acids (FAs) into C18 species. To define the precise molecular mechanism by which hepatic Elovl6 affects energy homeostasis and metabolic disease, we generated liver-specific Elovl6 knockout mice. Our study demonstrates the key role of hepatic Elovl6 in the regulation of the acyl-chain composition of ceramide and that C18:0-ceramide is a potent regulator of hepatic insulin signaling linked to Pnpla3-mediated NAFLD. To define the role of Elovl6 in pancreatic beta-cell and type 2 diabetes development, we generated beta-cell-specific Elovl6 knockout mice and assessed the effects of beta-cell specific Elovl6 deletion in db/db mice. The double mutant mice had a markedly increased β-cell mass, an adaptive increase in insulin and improved glycemic control. Taken together, inhibition of this elongase could be a new therapeutic approach for ameliorating insulin resistance and diabetes.
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