NOD 激活对脂肪细胞分化的影响。

The effects of NOD activation on adipocyte differentiation.

机构信息

Department of Nutrition, University of Tennessee, Knoxville, Tennessee, USA.

出版信息

Obesity (Silver Spring). 2013 Apr;21(4):737-47. doi: 10.1002/oby.20275.

DOI:10.1002/oby.20275

PMID:23712977

Abstract

OBJECTIVE

Obesity is associated with chronic inflammation. Toll-like receptors (TLR) and NOD-like receptors (NLR) are two families of pattern recognition receptors that play important roles in immune response and inflammation in adipocytes. It has been reported that TLR4 and TLR2 activation induce proinflammatory changes that impair adipocyte differentiation. However, the effects of activation of NOD1 and NOD2, the two prominent members of NLR, on adipocyte differentiation have not been studied.

DESIGN AND METHODS

3T3-L1 and human adipose-derived stem cells were tested for adipocyte differentiation in the presence or absence of NOD ligand. Adipocyte differentiation was evaluated by the adipocyte markers gene expression and Oil Red O staining for lipid accumulation.

RESULTS

Activation of NOD1, but not NOD2, by a synthetic ligand dose-dependently suppressed 3T3-L1 adipocyte differentiation as revealed by Oil Red O stained cell morphology, lipid accumulation, and attenuated gene expression of adipocyte markers (PPARγ, C/EBPα, SCD, FABP4, Adiponectin). Activation of NOD1, but not NOD2, induced NF-κB activation, which correlated with their abilities to suppress ligand-induced PPARγ transaction. Moreover, the suppressive effect by NOD1 activation was reversed by IκB super-repressor which blocks NF-κB activation. The suppression by NOD1 ligand C12-iEDAP on adipocyte differentiation was reversed by small RNA interference targeting NOD1, demonstrating the specificity of NOD1 activation. In contrast, activation of NOD1 and NOD2 both significantly suppressed adipocyte differentiation of human adipose-derived adult stem cells, demonstrating the species specific effects of NOD activation. In contrast to enhanced leptin mRNA by LPS and TNFα, NOD1 activation suppressed leptin mRNA in adipocytes, suggesting the differential effects of NOD1 activation in adipocytes.

CONCLUSIONS

Overall, our results suggest that NOD1 represents a novel target for adipose inflammation in obesity.

摘要

目的

肥胖与慢性炎症有关。Toll 样受体（TLR）和 NOD 样受体（NLR）是两种模式识别受体家族，在脂肪细胞的免疫反应和炎症中发挥重要作用。据报道，TLR4 和 TLR2 的激活诱导促炎变化，损害脂肪细胞分化。然而，NLR 中两个突出成员 NOD1 和 NOD2 的激活对脂肪细胞分化的影响尚未研究。

设计和方法

在存在或不存在 NOD 配体的情况下，用 3T3-L1 和人脂肪源性干细胞检测脂肪细胞分化。通过脂肪细胞标志物基因表达和油红 O 染色检测脂质积累来评估脂肪细胞分化。

结果

合成配体浓度依赖性激活 NOD1，但不激活 NOD2，可通过油红 O 染色细胞形态、脂质积累和减弱脂肪细胞标志物（PPARγ、C/EBPα、SCD、FABP4、脂联素）的基因表达来抑制 3T3-L1 脂肪细胞分化。NOD1 激活诱导 NF-κB 激活，这与其抑制配体诱导的 PPARγ 转导的能力相关。此外，IκB 超级抑制剂可逆转 NOD1 激活的抑制作用，该抑制剂可阻断 NF-κB 激活。NOD1 配体 C12-iEDAP 对脂肪细胞分化的抑制作用被针对 NOD1 的小 RNA 干扰逆转，表明 NOD1 激活的特异性。与 LPS 和 TNFα 增强瘦素 mRNA 相反，NOD1 激活抑制脂肪细胞中的瘦素 mRNA，提示 NOD1 激活在脂肪细胞中的差异作用。