The Effect Of ?3 Adrenergic Receptor Expression And NE Intervention On Human Adiposity And Adipocyte Differentiation

Objectives:Brown adipose tissue(BAT)can dissipate chemical energy in the form of heat through the activation of uncoupling protein 1(UCP-1),thereby decreasing the occurrence of the obesity.Classical brown adipocytes mainly resided in infants and rodent,and rarely in adults,but active brown adipose tissue was found in adult through 18F-FDG-PET/CT,known as human brown adipose t:issue(hBAT),which was constituted with different perception of white,beige and brown adipocytes.The amount of hBAT inversly correlated with BMI and age.Some researchers have focused on the study of adipose tissue browning in human to treat obesity.?3 adrenergic receptor(P3AR)is a dominant signaling pathway in the process of adipose tissue browning.But the function of hBAT in obese patlients is lower compared with non-obese individuals during the process of sympathetic nerve stimulation and the underlying mechanisms remain poorly understood.Therefore,the present study would examine the adipocyte?3AR expression levels in overweight individuals and detect the beige adipocytes specific genes(PRDM16,PGC1? and UCP-1)expression with or without the the intervention of norepinephrine(NE)during preadipogenic differentiation.This study aims to explore whether there is a decrease in adipocyte ?3AR expression at the early stage of the obesity,which may result in the compromised ability of beige adipocytes activation and adipose tissue browning,and eventually contribute to the development of obesity.Methods:Omental adipose tissue samples(3-5g)were collected from 81 patients who underwent abdominal surgery.Participants were divided into two subgroups according to BMI,normal weight group[BMI<25(kg/m2)]and overweight group[25<BMI<30(kg/m2)].The adipose tissue samples were separated into mature adipocytes and stromal vascular cells,P3AR mRNA and protein expression levels in mature adipocytes and stromal vascular cells were examined by quantitative real-time PCR(qRT-PCR)and western blot(WB).The expression levels of Ebf2 mRNA were detected in preadipocytes before differentiation.PRDM16,PGCla and UCP-1 expression levels were detected by qRT-PCR during preadipocytes differentiation with or without the treatment of 1 ?M NE for 4 hours.Results:81 subjects were included in the present study.?3AR mRNA and protein expression levels in mature adipocytes were examined from 48 and 27 specimens respectively.?3AR protein levels of stromal vascular cells were analyzed from 50 specimens,preadipocytes differentiation and intervertion experiments used the preadipocytes from 10 specimens.The results showed that ?3AR mRNA(P=0.021)and protein(P=0.032)expression in mature adipocytes were significantly higher in normal weight group compared to overweight group.Similar result was found in stromal vascular cells ?3AR protein expression(P=0.022).An inverse correlation was verified between ?3AR mRNA expression in mature adipocytes and BMI(r=-0.346,P=0.016).The expression levels of Ebf2,the marker of beige adipocytes differentiation,in preadipocytes were lower in overweight group compared with normal weight group(P=0.031).PRDM16 mRNA expression started to increase at day 8,and reached to maximum expression level at day 11 during preadipocyte differentiation in normal weight group,but we did not see this trend in overweight group.There were also a increase in PGCla mRNA and UCP-1 mRNA expression during preadipocyte differentiation,but no significant difference between normal weight group and overweight group(P>0.05).In normal weight group,PGC1? mRNA and UCP-1 mRNA expression levels in NE intervention group were higher(P<0.05)than that in control,whereas there was not statistical difference in PRDM16 mRNA expression levels with or without NE intervention.In overweight group,no statistical difference was found in PRDM16 mRNA?PGC1?amRNA?UCP-1 mRNA after NE treatment.Conclusions:Overweight individuals had obviously lower ?3AR expression in adipose tissue stromal vascular cells and mature adipocytes compared to normal weight ones in present study,which may cause the compromised hBAT activity in obesity.And the beige adipocyte specific gene-PGCla and UCP-1 expression reached to peak at the mid-term and late stage of preadipocyte differentiation in normal weight individuals after NE treatment,but no significant increase in beige adipocyte specific gene expression was found in overweight individuals,which also verified that important role of P3AR function in adipocyte beiging.And ?3AR expression levels were down regulated before the onset of obesity,which indicated that(33AR disfunction maybe the reason of obesity,but not result.So interference with the ?3AR pathway may provide the promising potential target for the treatment of obesity.