Open AccessInhibition of preadipocyte differentiation and adipogenesis by zinc‐α2‐glycoprotein treatment in 3T3‐L1 cells
Author(s) -
Zhu HuiJuan,
Ding HuiHua,
Deng JieYing,
Pan Hui,
Wang LinJie,
Li NaiShi,
Wang XiangQing,
Shi YiFan,
Gong FengYing
Publication year - 2013
Publication title -
journal of diabetes investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.089
H-Index - 50
eISSN - 2040-1124
pISSN - 2040-1116
DOI - 10.1111/jdi.12046
Subject(s) - adipogenesis , 3t3 l1 , fatty acid synthase , endocrinology , medicine , oil red o , transfection , microbiology and biotechnology , adipose tissue , biology , biochemistry , lipid metabolism , gene
Aims/Introduction Zinc‐α2‐glycoprotein ( ZAG ) is associated with the loss of adipose tissue in cancer cachexia, and has recently been proposed to be a candidate factor in the regulation of bodyweight. The aim of the study was to investigate the effects of ZAG on the proliferation and differentiation of 3T3‐L1 preadipocytes. Materials and Methods 3‐(4,5‐Dimethylthiazol‐2‐yl) 2,5‐diphenyl tetrazolium bromide ( MTT ) spectrophotometry, Oil Red O staining, intracellular triglyceride assays, real‐time quantitative reverse transcription polymerase chain reaction and transient transfection methods were used to explore the action of ZAG . Results Ectopic ZAG expression significantly stimulates 3T3‐L1 cells proliferation in a dose‐ and time‐dependent manner. The maximum influence of ZAG on proliferation was 1.43‐fold higher than what was observed in control cells. This effect was observed 144 h after transfection with 0.16 μg of murine ZAG ( mZAG ) plasmid ( P < 0.001). The intracellular lipids content in mZAG over‐expressing cells were decreased as much as 37% when compared with the control cells after differentiation ( P < 0.05, P < 0.01). The messenger ribonucleic acid levels of peroxisome proliferators‐activated receptor‐γ (PPARγ), CCAAT enhancer‐binding protein‐α (C/EBPα) and the critical lipogenic gene, fatty acid synthase (FAS), are also downregulated by up to 50% in fully differentiated ZAG‐treated adipocytes. ZAG suppresses FAS messenger ribonucleic acid expression by reducing FAS promoter activity. Conclusions Zinc‐α2‐glycoprotein stimulates the proliferation and inhibits the differentiation of 3T3‐L1 murine preadipocytes. The inhibitory action of ZAG on cell differentiation might be a result of the attenuation of the expression of PPAR γ, C/ EBP α and the lipogenic‐specific enzyme FAS by reducing FAS promoter activity.