利拉鲁肽促进脂肪细胞褐化机制的实验研究  

Mechanism of liraglutide-induced adipocyte browning

作　　者：刘昱彤 刘睿涵 周翔 王小毛 张杰[1] 曹剑[1] Liu Yutong;Liu Ruihan;Zhou Xiang;Wang Xiaomao;Zhang Jie;Cao Jian(Fourth Department of Healthcare,Second Medical Center·National Clinical Research Center for Geriatric Diseases,Chinese PLA General Hospital,Beijing 100853,China)

机构地区：[1]解放军总医院第二医学中心保健四科、国家老年疾病临床医学研究中心,北京100853

出　　处：《中华老年心脑血管病杂志》2025年第4期510-514,共5页Chinese Journal of Geriatric Heart,Brain and Vessel Diseases

基　　金：北京市自然科学基金(7232157)。

摘　　要：目的探讨利拉鲁肽(liraglutide,Lira)对脂肪细胞褐化的调控作用及其潜在分子机制。方法脂肪间充质干细胞诱导成脂,棕榈酸模拟高脂环境,慢病毒转染沉默过氧化物酶体增殖物激活受体γ共激活因子1α(peroxisome proliferator-activated receptor gamma coactivator 1-Alpha,PGC1α)基因表达。将脂肪细胞分为对照组、Lira组(100 nmol/L的Lira溶液处理)、棕榈酸组(200 nmol/L的棕榈酸溶液处理)、棕榈酸+Lira组(100 nmol/L的Lira溶液+200 nmol/L棕榈酸溶液处理)、随机小干扰RNA(scrambled small interfering RNA,scrambled siRNA)组、scrambled siRNA+Lira组、沉默PGC1α小干扰RNA(siRNA PGC1α)组、siRNA PGC1α+Lira组(n=3)。Scrambled siRNA组、siRNA PGC1α组相应慢病毒转染后给予200 nmol/L的棕榈酸溶液处理;scrambled siRNA+Lira组、siRNA PGC1α+Lira组相应慢病毒转染后给予100 nmol/L的Lira溶液+200 nmol/L的棕榈酸溶液处理细胞。采用荧光定量聚合酶链反应和蛋白免疫印迹法检测细胞解偶联蛋白1(uncoupling protein 1,UCP-1)、PR结构域蛋白16(PR domain containing 16,Prdm16)、血管紧张素原(angiotensinogen,Agt)、脂联素的基因及蛋白表达,以及腺苷酸活化蛋白激酶(adenosine 5′-monophosphate-activated protein kinase,AMPK)及磷酸化AMPK(phosphorylated AMPK,p-AMPK)表达。结果与对照组比较,棕榈酸组Agt、脂联素蛋白及mRNA表达和Lira组UCP-1、Prdm16蛋白及mRNA明显升高,棕榈酸组UCP-1,Prdm16蛋白及mRNA表达和Lira组Agt、脂联素蛋白及mRNA表达明显下降,差异有统计学意义(P<0.05);与棕榈酸组比较,棕榈酸+Lira组UCP-1、Prdm16蛋白及mRNA表达明显升高,Agt、脂联素蛋白及mRNA表达明显降低,差异有统计学意义(P<0.05)。Scrambled siRNA+Lira组脂肪细胞UCP-1、Prdm16蛋白表达和siRNA PGC1α组Agt、脂联素蛋白表达显著高于scrambled siRNA组,scrambled siRNA+Lira组Agt、脂联素蛋白表达和siRNA PGC1α组UCP-1蛋白表达显著低于scrambled siRNA组(P<0.05)。与sObjective To investigate the regulatory effects of liraglutide(Lira)on adipocyte browning and its underlying molecular mechanisms.Methods Adipose-derived mesenchymal stem cells were induced to differentiate with palmitic acid(PA)simulating a high-fat environment and lentiviral transfection to silence the expression of PGC1α.The cell groups included control,Lira(100 nmol/L),PA(200 nmol/L),PA+Lira,scrambled siRNA,scrambled siRNA+Lira,siRNA PGC1α,and siRNA PGC1α+Lira groups(n=3).After corresponding treatments were given,quantitative PCR and Western blotting were employed to detect the mRNA and protein expression levels of UCP-1,Prdm16,Agt,and adiponectin,as well as AMPK and p-AMPK.Results Compared to the control group,the PA group had significantly increased expression of Agt and adiponectin but decreased UCP-1 and Prdm16 at protein and mRNA levels,and the Lira group showed obviously increased protein and mRNA levels of UCP-1 and Prdm16 but decreased Agt and adiponectin levels(P<0.05).Addition of Lira treatment resulted in increments in UCP-1 and Prdm16 while declines Agt and adiponectin at both mRNA and protein levels when compared with the levels in the PA group(P<0.05).In comparison to the scrambled siRNA group,the siRNA PGC1αgroup showed decreases in UCP-1 and Prdm16 expression,accompanied by increases in Agt and adiponectin levels(P<0.05),similar results were observed in the scrambled siRNA+Lira group(P<0.05).The p-AMPK/AMPK ratio was significantly increased in the scrambled siRNA+Lira group(1.415±0.176 vs 0.837±0.049,P<0.05),but decreased in the siRNA PGC1αgroup(0.534±0.035 vs 0.837±0.049,P<0.01)when compared with the scrambled siRNA group.Conclusion Lira promotes adipocyte browning and improves lipid metabolism disorders in a high-fat environment by activating the AMPK/PGC1αsignaling pathway.

关 键 词：利拉鲁肽 脂肪细胞 白色 脂肪细胞 棕色 棕榈酸 

分 类 号：R73[医药卫生—肿瘤]