Budget Amount *help |
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2022: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2021: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2020: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2019: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
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Outline of Final Research Achievements |
To clarify the role of Hmg-CoA reductase (Hmgcr) in macrophages in the development of insulin resistance and hepatic steatosis, we generated mice lacking Hmgcr in macrophages by crossing floxed Hmgcr mice with imce expressiong Cre recombinase under the control of lysozyme promoter (M-HmgcrKO). After feeding M-Hmgcr with high fat diet, M-HmgcrKO mice had better glucose tolerance, insurlin sensitivity and hepatic steatosis compared with wild-type mice. The number of maccropahges were significantly decreased in M-HmgcrKO mice compared with wild-tyoe mice, thereby contributing to reduced inflamation. Macrophages taken from M-HmgcrKO mice had reduced migratory activity compared with wild-type macrophages. Membrane-bound RhoA or Rac1 were increased in the macrophages from M-HmgcrKO mice compared with wild-type macrophages. We speculate that pharmacological or genetic targeting Hmgcr would be a promosing strategy to treat metabolic abnormalities in type 2 diabetes and/or obesity.
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