巨噬細胞對於脂肪細胞分化及能量代謝之影響

肥胖屬低度慢性發炎反應，使浸潤於脂肪組織之巨噬細胞(adipose tissue macrophages; ATMs)從抗發炎型(anti-inflammatory phenotype; M2)轉變為促發炎型(pro-inflammatory phenotype; M1)，進而影響胰島素作用使脂肪細胞產生胰島素阻抗性(insulin resistance)。根據先前的研究結果，高度表現第四型介白素(interleukin-4; IL-4)之小鼠，其脂肪組織中有較多M2 ATMs浸潤的現象。因此本研究欲探討在活體外情況下，M2巨噬細胞對脂肪細胞之細胞分化與能量代謝之影響。在建立細胞可從脂肪前驅細胞(preadipocytes)分化為成熟脂肪細胞的模式後，利用M2-conditioned medium培養脂肪前驅細胞後發現成熟脂肪細胞內的油滴減少，因此推論M2-conditioned medium可能影響脂肪細胞的分化過程。藉由觀察脂肪細胞分化過程中的標幟分子C/EBP-β、PPAR-γ和aP2之mRNA表現，得知脂肪細胞分化過程未受到顯著影響，因此進一步推論M2-conditioned medium可能影響脂肪細胞的油滴形成或脂質代謝。藉由觀察油滴包覆蛋白perilipin及參與脂質代謝酵素fatty acid synthase和hormone-sensitive lipase之mRNA表現，發現perilipin之表現明顯較陽性對照組低，表示在油滴包覆蛋白之表現量或是油滴形成過程可能受到抑制，進而導致成熟脂肪細胞內的油滴減少，未來仍需做進一步地釐清相關機制。

關鍵字

第四型介白素；胰島素阻抗性；巨噬細胞；脂肪細胞

並列摘要

Obesity is a chronic and low-grade inflammation, which causes insulin resistance, will affect the functions of adipocytes, attract macrophages to infiltrate into adipose tissue and make macrophages change their phenotype – from anti-inflammatory macrophages (M2) to pro-inflammatory macrophages (M1). These two different types of macrophage may play different roles in different stages of obesity. In our previous studies, the interleukin-4 (IL-4)-overexpressed mice showed there were more M2 macrophages accumulated in their adipose tissue. Therefore, we want to explore the effects of M2 macrophages on adipogenesis and metabolism of adipocytes by using an in vitro differentiation assay of 3T3-L1 with M2-conditioned medium. Our results showed there were fewer oil droplets accumulated in the M2-conditioned group than positive control, but it seemed there were no effects on the process of adipocyte differentiation and lipid metabolism by observing the expression levels of adipocyte differentiation and lipid metabolism markers, C/EBP-β, PPAR-γ, aP2, fatty acid synthase and hormone-sensitive lipase. However, there were significant decreases in lipid droplet formation marker, perilipin, between positive control and M2-conditioned group. It seemed that the expressions of perilipin or the process of lipid droplet formation may be inhibited by M2-conditioned medium. The detail molecular mechanism of this phenomenon is under further investigation.

並列關鍵字

interleukin-4 ； knsulin resistance ； macrophage ； adipocytes

參考文獻

Ailhaud G, Grimaldi P, Négrel R. Cellular and molecular aspects of adipose tissue development. Annu Rev Nutr 12: 207-233, 1992.

Borg J, Klint C, et al. Perilipin is present in islets of Langerhans and protects against lipotoxicity when overexpressed in the beta-cell line INS-1. Endocrinology 150(7): 3049-57, 2009

Chang YH, Ho KT, Lu SH, Huang CN, Shiau MY. Regulation of glucose/lipid metabolism and insulin sensitivity by interleukin-4. Int J Obes (Lond) 36(7): 993-8, 2012.

Christy RJ, Kaestner KH, Geiman DE, Lane MD. CCAAT/enhancer binding protein gene promoter: binding of nuclear factors during differentiation of 3T3-L1 preadipocytes. Proc Natl Acad Sci U S A 88(6): 2593-2597, 1991.

Clarke SL, Robinson CE, Gimble JM. CAAT/enhancer binding proteins directly modulate transcription from the peroxisome proliferator-activated receptor gamma 2 promoter. Biochem Biophys Res Commun 240(1): 99-103, 1997.

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巨噬細胞對於脂肪細胞分化及能量代謝之影響

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