| Budget Amount *help |
¥3,890,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥390,000)
Fiscal Year 2007: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2006: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Research Abstract |
In the present study, to elucidate the molecular mechanisms of adipocyte-macrohphage interaction, we examined the relationship between adipocytokine dysregulation and the function of monocyte and the effect of anti-insulin resistant agents on the function of monocyte in the obesity and metabolic syndrome.
1. Examination using the THP-1 cell : In THP-1 cell, the incubation with of PPAR ligand ; TZDs(Pioglitazone 6μM) for 24 hours significantly decreased the expression of IL-6 and MMP-9 and the administration of EPA 50 μM for 24 hours significantly decreased CD14, TNFα, MCP-1, MMP-9 and TLR4 and increased adiponectin.
2. Examination using the human monocyte : We examined monocyte function after separating peripheral blood monocyte cells by MACS or Ficoll-Paque method from blood in control, obesity and diabetes. (1) The expressions of TNF-α, IL-6 and MCP-1 detected by real-time PCR in monocyte were higher in obesity and diabetes compared to control. (2) there is no significant difference between the expression and activity of CD14, a specific marker of monocyte, detected by FACS between control and obesity, however in diabetic patients the expression and activity of CD14 and inactive M2 Macrophage was significantly lower. (3) Administrating TZDs for 3 months, the expression of TNF-α and CD14 activity were improved
3. Clinical Study : We revealed that highly purified EPA reduces small, dense LDL(sdLDL), remnants, and CRP(Diabetes Care 27 : 144, 2007) and increases adiponectin secretion in rodent models of obesity and human obese subjects, possibly through the improvement of obese-related adipose tissue inflammation(ATVB 27 : 1918, 2007).
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