| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Outline of Final Research Achievements |
Metabolic imbalance is associated with diabetes and linked with dysfunctions of nutrient-sensors such as AMPK. Additionally pro-inflammatory cytokines such as TNFα contributes to chronic low-grade inflammation and insulin resistance. Previously we reported that Fyn knockout mice display increased energy expenditure due to increased AMPK activity. More recently, we demonstrated that Fyn regulates AMPK activity through Y426 phosphorylation of the α subunit. We then examined the crosstalk between Fyn and pro-inflammatory cytokines on AMPK regulation. Prolonged incubation with TNFα suppressed AICAR stimulated T172 α subunit phosphorylation. In parallel, TNFα increased Fyn kinase activity and siRNA knockdown of Fyn prevented the chronic TNFa inhibition of AICAR-stimulated AMPK T172 α subunit phosphorylation. Taken together, these data suggest that prolonged stimulation of TNFα blunts AICAR dependent AMPK activation through Fyn-dependent tyrosine phosphorylation of AMPK α subunit.
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