Mechanism of liraglutide-induced adipocyte browning

Liu Yutong; Liu Ruihan; Zhou Xiang; Wang Xiaomao; Zhang Jie; Cao Jian

doi:10.3969/j.issn.1009-0126.2025.04.024

Abstract：Objective To investigate the regulatory effects of liraglutide(Lira)on adipocyte brown-ing 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 lenti-viral 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 expres-sion 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 PGC1α group showed decreases in UCP-1 and Prdm16 expression,accompanied by increa-ses 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 PGC1α group(0.534±0.035 vs 0.837±0.049,P＜0.01)when compared with the scram-bled siRNA group.Conclusion Lira promotes adipocyte browning and improves lipid metabolism disorders in a high-fat environment by activating the AMPK/PGC1α signaling pathway.