Liraglutide Promotes White Adipose Browning Via Downregulating MicroRNA 27b

Objective:To study the effect of liraglutide on the browning of WAT from high fat fed rats and adipocytes derived from 3T3-L1 cells,and to investigate its possible mechanism.Methods:1 Animal studyForty SD rats were randomLy divided into five groups,low?middle and high doses of liraglutide groups were subcutaneously injected with corresponding doses of liraglutide,Con group and HF group received equal volume of normal saline.At the end of 12 th week of drug intervention,the rats were weighed and then killed.Epididymal white adipose tissue was collected.The morphological changes of white adipose tissue were observed by HE staining.Real-Time PCR was used to detect the expression of miR-27 b.Real-Time PCR and Western Blot were respectively used to detect the mRNA expression and protein expression of UCP1,PRDM16,CEBP?,CIDEA and PGC-1?.2 Cell study3T3-L1 preadipocytes were resuscitated and induced to differentiate into mature adipocytes.Mature adipocytes were randomly divided into three groups,negative control treatment or different doses of liraglutide intervention was given respectively.Triglyceride level was detected by oil red O staining and triglyceride assay kit.Real-Time PCR was used to detect the mRNA expression of miR-27 b.The mRNA expression and protein expression of UCP1,PRDM16,CEBP?,CIDEA and PGC-1? were detected by Real-Time PCR and Western Blot respectively.Mature adipocytes were randomly divided into control group and transfection group to transfect mi R-27 b,and then each group was randomly divided into two groups.Cells were treated with Liraglutide and negative control for 48 hours respectively,finally collected cells.PCR and Western Blot were used to detect the mRNA and protein expression of UCP1,PRDM16,CEBP?,CIDEA and PGC-1?.Results:1 Animal studyAfter 12 weeks of drug intervention,the body weight of rats in HF group was significantly increased compared to Con group(P<0.05).The body weight of liraglutide groups was decreased than Con group and HF group(P<0.05).Compared with HF group,adipocytes were smaller in liraglutide groups.There was no obvious difference of morphology compared with Con group.There was no significant difference in indexes above among liraglutide groups(P>0.05).Compared with Con group,the expression of miR-27 b in white adipose tissue of rats in HF group was significantly increased(P<0.05).Compared with HF group,the expression of miR-27 b in liraglutide groups decreased significantly(P<0.05).There was no significant difference in miR-27 b expression among liraglutide groups(P>0.05).Compared with Con group,the mRNA expression and protein expression of brown marker genes: UCP1,PRDM16,CEBP?,CIDEA and PGC-1? in white adipose tissue of rats was down-regulated in HF group(P<0.05).Compared with HF group,the mRNA expression and protein expression of UCP1,PRDM16,CEBP?,CIDEA and PGC-1? of liraglutide groups were up-regulated(P<0.05).There was no significant difference in the m RNA expression and protein expression of UCP1,PRDM16,CEBP?,CIDEA and PGC-1? among liraglutide groups(P>0.05).2 Cell studyCompared with Vechile group,the volume of lipid droplets and the content of triglyceride in 1u M and 10 uM groups were decreased(P<0.05).Compared with Vechile group,the expression of miR-27 b in 1uM and 10 uM groups was decreased(P<0.05),the mRNA expression and protein expression of UCP1,PRDM16,CEBP?,CIDEA and PGC-1? in 1u M and 10 uM groups were increased(P<0.05).Compared with mimic-nc+con group,the mRNA expression and protein expression of UCP1,PRDM16,CEBP?,CIDEA and PGC-1? in miR-27b+con group was decreased(P<0.05).The mRNA expression and protein expression of UCP1,PRDM16,CEBP?,CIDEA and PGC-1? in miR-27b+Lira group was increased than mi R-27b+con group(P<0.05).Conclusion:Liraglutide can reduce the body weight of high fat fed rats,and reduce the lipid content in high fat diet rats and 3T3-L1 mature adipocytes.Liraglutide can promote the browning function of white adipose tissue and may via down-regulation of miR-27 b.