Reduced Beige Adipogenic Potential In Subcutaneous Adipose Tissue From Obese Individuals

Objectives:Obesity has been epidemic around the world for decades,and is an independent risk factor for cardiovascular diseases,Type 2 diabetes and some of the malignant tumors.There are two categories adipose tissues with opposite function to human fuel metabolism:white adipose tissue(WAT)charges for energy reservation,while brown adipose tissue(BAT)can dissipate stored energy through uncoupling protein 1(UCP1)and release as heat.BAT is rare in adults.However,some adipocytes in WAT could differentiate into brown-like adipocytes which possess similar thermogenic function under cold circumstance or sympathetic excitation,which were called beige adipocytes,and this process was named as WAT browning.Thermogenesis function has made beige adipocytes an attractive target for obesity.Experiments in rodents or humans have validated that BAT activity is negative related to body mass index(BMI),age and hyperlipemia by 18F-fluorodeoxyglucose PET/CT approach.The present study aims to verify if the adipocytes derived from subcutaneous adipose tissue of obesity have the compromised browning potential compared to normal weight individuals.Methods:Preadipocytes were isolated from subcutaneous fat tissues and induced into white or beige adipocytes.According to BMI,the participants that undertook plastic surgeries were divided into two groups:non-obese group[BMI≤24(kg/m2)]and obesity group[BMI>28(kg/m2)].The expression of UCP1 protein and beige adipocyte marker genes were detected via western blot and quantative real time PCR.Cellular oxygen consumption rate(OCR)and lipolysis were measured using extra-cellular flux bioanalyzer and enzyme-linked immuosorbent assay respectively.Results:In non-obese group(NW group),the expression of UCP1 was higher than that in obesity group(OB group).Besides,UCP1 protein expression,thermogenesis genes,including UCP1,PRDM16,PGC-1α,FGF21,CIDEA were upregulated and OCR were enhanced in beige induced adipocytes compared with white induced adipocytes in NW group(P<0.01).But in obesity group,except lipolysis(P<0.01),UCP1 protein,most brown or beige marker genes,and oxygen consumption rate did not increase significantly compared with induced white adipocytes(P>0.05).However,whether in beige or white induced adipocytes,UCP1 protein,brown/beige specific genes,OCR,and lipolysis were significantly higher than that in OB group.(P<0.01).Conclusion:It was shown that marker protein were downregulated in subcutaneous adipose tissue from obesity patients at cellular level,which indicated reduced BAT activity in obese people.With the presence of β3-adrenergic agonist in induction cocktail,beige adipoctyes specific protein and genes were improved significantly in beige induced adipocytes in NW group compared with white induced adipocytes,but there was no between white or beige induced adipocytes in OB group.Besides,OCR and lipolysis function were reduced in OB group.Collectively,the results demonstrated that the sensitivity of preadipocytes to beige induction were reduced in obesity patients.Adipocytes β3-adrenergic receptor may have been down-regulated in obesity patients because β3-adrenergic agonist was the dominant intervention reagent in induction cocktail,which also indicated that the regulation of BAT activity needed independent adrenergic pathway.