PMID- 29789508
OWN - NLM
STAT- MEDLINE
DCOM- 20180918
LR  - 20211204
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 19
IP  - 6
DP  - 2018 May 23
TI  - Dual Effects of Metformin on Adipogenic Differentiation of 3T3-L1 Preadipocyte in 
      AMPK-Dependent and Independent Manners.
LID - 10.3390/ijms19061547 [doi]
LID - 1547
AB  - Metformin has been reported to have body weight lowering effects while treating 
      type 2 diabetes. However, limited studies examined the effects of metformin on 
      adipogenesis in vitro, and available data are inconclusive and contradictory. In 
      this study, we examined the effects of a variety of concentrations of metformin 
      on adipocyte differentiation of 3T3-L1 preadipocytes and found metformin exhibits 
      a dual effect on adipogenesis. Metformin at lower concentrations (1.25(-)2.5 mM) 
      significantly induced adipogenesis while at higher concentrations (5(-)10 mM) 
      metformin significantly inhibited adipogenesis in 3T3-L1 cells. The biphasic 
      effect of different doses of metformin on adipogenesis was accompanied by 
      increasing or decreasing the expression of adipogenic and lipogenic genes 
      including peroxisome proliferator-activated receptor (PPARgamma), CCAAT/enhancer 
      binding protein alpha (C/EBPalpha), and fatty acid synthase (FASN) at both messenger RNA 
      (mRNA) and protein levels. Furthermore, only the higher concentrations of 
      metformin induced the phosphorylation of adenosine 5'-monophosphate 
      (AMP)-activated protein kinase (AMPK), p38, and c-Jun N-terminal kinase (JNK) and 
      reduced the phosphorylation of extracellular regulated protein kinases (ERK) and 
      Akt. Pretreatment with compound C, a specific AMPK inhibitor, significantly 
      countered high concentration of metformin-induced inhibition of adipogenesis. 
      Taken together, these findings demonstrate that the effect of metformin on 
      adipocyte differentiation is biphasic and dose-dependent. Lower concentrations of 
      metformin induce adipogenesis, which could be mediated in an AMPK-independent 
      manner, while higher concentrations of metformin inhibit adipogenesis via AMPK 
      activation.
FAU - Chen, Dian
AU  - Chen D
AD  - College of Pharmaceutical Science, Zhejiang Chinese Medical University, 548 
      Binwen Road, Hangzhou 310053, China. chendian_zcmu@163.com.
FAU - Wang, Ying
AU  - Wang Y
AD  - College of Pharmaceutical Science, Zhejiang Chinese Medical University, 548 
      Binwen Road, Hangzhou 310053, China. wangying19870523@163.com.
FAU - Wu, Kaikai
AU  - Wu K
AD  - College of Pharmaceutical Science, Zhejiang Chinese Medical University, 548 
      Binwen Road, Hangzhou 310053, China. 15990099051@163.com.
FAU - Wang, Xingya
AU  - Wang X
AD  - College of Pharmaceutical Science, Zhejiang Chinese Medical University, 548 
      Binwen Road, Hangzhou 310053, China. xywang@zcmu.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20180523
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (CCAAT-Enhancer-Binding Protein-alpha)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (PPAR gamma)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 9100L32L2N (Metformin)
RN  - EC 2.3.1.85 (Fatty Acid Synthase, Type I)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.3 (AMP-Activated Protein Kinase Kinases)
RN  - EC 2.7.12.2 (MAP Kinase Kinase 4)
SB  - IM
MH  - 3T3 Cells
MH  - AMP-Activated Protein Kinase Kinases
MH  - Adipocytes/cytology/*drug effects/metabolism
MH  - *Adipogenesis
MH  - Animals
MH  - CCAAT-Enhancer-Binding Protein-alpha/genetics/metabolism
MH  - Fatty Acid Synthase, Type I/genetics/metabolism
MH  - Hypoglycemic Agents/*pharmacology
MH  - MAP Kinase Kinase 4/genetics/metabolism
MH  - Metformin/*pharmacology
MH  - Mice
MH  - PPAR gamma/genetics/metabolism
MH  - Protein Kinase Inhibitors/pharmacology
MH  - Protein Kinases/*metabolism
MH  - p38 Mitogen-Activated Protein Kinases/genetics/metabolism
PMC - PMC6032223
OTO - NOTNLM
OT  - 3T3-L1 preadipocyte
OT  - AMPK
OT  - MAPKs
OT  - adipogenesis
OT  - metformin
COIS- The authors declare no conflict of interest.
EDAT- 2018/05/24 06:00
MHDA- 2018/09/19 06:00
PMCR- 2018/06/01
CRDT- 2018/05/24 06:00
PHST- 2018/03/12 00:00 [received]
PHST- 2018/05/14 00:00 [revised]
PHST- 2018/05/18 00:00 [accepted]
PHST- 2018/05/24 06:00 [entrez]
PHST- 2018/05/24 06:00 [pubmed]
PHST- 2018/09/19 06:00 [medline]
PHST- 2018/06/01 00:00 [pmc-release]
AID - ijms19061547 [pii]
AID - ijms-19-01547 [pii]
AID - 10.3390/ijms19061547 [doi]
PST - epublish
SO  - Int J Mol Sci. 2018 May 23;19(6):1547. doi: 10.3390/ijms19061547.