长链脂肪酸通过GPR120对脂肪细胞炎症、内质网应激及胰岛素信号分子的影响

Long chain fatty acids on the fat cells inflammation,endoplasmic reticulum stress and insulin signaling molecules by affecting GPR120

目的观察长链脂肪酸对脂肪细胞GPR120的作用及对脂肪细胞炎症、内质网应激及胰岛素信号分子的影响。方法体外培养3T3-L1前脂肪细胞,采用1μM地塞米松、1μg/ml胰岛素和10%加强型小牛血清的DMEM培养基诱导为分化3T3-L1脂肪细胞,采用100Μm PA刺激2 h后,采用Western blot方法检测GPR120、XBP1S、PERK、P-PERK、IRE-1α、P-IRE-1α、IKKβ、p-IKKβ、JNK1、P-JNK1、JNK2和P-JNK2蛋白表达水平。加入含有100ng/ml胰岛素的DMEM培养基,孵育15 min,采用Western blot方法检测IR、P-IR、IRS-1、p-IRS、Akt和P-Akt蛋白表达水平。结果在PA的刺激下,GPR120、XBP1S、PERK、P-PERK、IRE-1α、P-IRE-1α、IKKβ、p-IKKβ、JNK1、PJNK1、JNK2和P-JNK2表达显著提高(P<0.05),IR、P-IR、IRS-1、p-IRS-1、Akt和P-Akt蛋白表达水平显著下降(P<0.05),而使用GPR120阻滞剂LGW9508可以抑制该过程。结论长链饱和脂肪酸PA可通过上调GPR120蛋白的表达,诱导脂肪内质网应激反应、炎症反应和胰岛素抵抗。

Objective To examine the role of long chain fatty acids and GPR120 on adipocytes inflammation,endoplasmic reticulum stress and insulin signaling molecules. Methods We cuhured 3T3-L1 pre-adipocytes, using 1 p.M dexametha- sone, 1 μg/ml insulin and DMEM medium 10% fetal bovine serum inducted differentiation of 3T3-L1 adipocytes. After 2 h 100 Mm PA stimulation, use western blot method to detect GPR120, XBP1 S, PERK, P-PERK, IRE-1α, P-IRE-1 α, IKKβ, p-IKKβ ,JNK1, P-JNK1, JNK2 and P-JNK2 protein expression levels. Add DMEM medium containing 100 ng/ml insulin, incubate 15 rain,and use western blot method to detect IR, P-IR, IRS-1 ,p-IRS, Akt and P-Akt protein expression levels. Results Under the stimulation of PA, GPR120, XBP1 S, PERK, P-PERK, IRE-1 a, P-IRE-1 a, IKKβ, p-IKKβ, JNK1, P- JNK1, JNK2 and P-JNK2 expression significantly increased （ P 〈 0.05 ） , IR, P-IR, IRS-1, p-IRS-1, Akt and P-Akt protein levels decreased significantly（ P 〈 0.05 ） ,while using GPR120 LGW9508 blockers can inhibit this process. Conclusion Long chain saturated fatty acids can increase PA GPR120 protein expression ,and induce fat endoplasmic reticulum stress response, inflammation and insulin resistance.