PMID- 22114064
OWN - NLM
STAT- MEDLINE
DCOM- 20120202
LR  - 20211021
IS  - 1535-3699 (Electronic)
IS  - 1535-3702 (Print)
IS  - 1535-3699 (Linking)
VI  - 236
IP  - 12
DP  - 2011 Dec
TI  - Homocysteine inhibits adipogenesis in 3T3-L1 preadipocytes.
PG  - 1379-88
LID - 10.1258/ebm.2011.011234 [doi]
AB  - Hyperhomocysteinemia (HHcy) is a characteristic metabolic abnormality in several 
      pathological conditions, including hypertension, diabetes and alcoholic liver 
      disease. Emerging evidence indicates that adipose tissue contributes to HHcy and 
      homocysteine (Hcy) conversely affects adipose tissue function. However, the 
      specific effect of Hcyon adipogenesis is poorly understood. In the present study, 
      we investigated the effects and mechanisms of Hcy on adipogenic process using 
      3T3-L1 preadipocytes, a well-established in vitro model for the study of 
      adipogenesis. Confluent mouse embryo 3T3-L1 preadipocytes (D0) were exposed to 
      differentiation cocktail for three days (D3). Then, cells were transferred to 
      insulin-containing medium and re-fed every two days. Maturation of adipocytes was 
      confirmed by Oil Red O staining of lipid droplets on day 7. Exogenous Hcy was 
      added to the culture medium on either D0 or D3. At day 7, adipogenesis indices 
      were measured. Our data indicated that both Hcy addition protocols suppressed 
      adipogenic process, evidenced by decreased lipid accumulation and downregulated 
      gene expressions of adipocyte protein 2 and peroxisome proliferator-activated 
      receptor gamma (PPAR-gamma), implying that Hcy exerted inhibitory effects on both 
      mitotic clonal expansion (MCE) stage and differentiation stage. Further study 
      showed that Hcy suppresses MCE via decreasing retinoblastoma protein 
      phosphorylation and E2F-1 protein expression. To delineate the critical 
      involvement of PPAR-gamma in Hcy-induced suppression on adipogenesis, we employed 
      rosiglitazone, a specific PPAR-gamma agonist, to replace insulin for the 
      inductive stimulus of adipogenesis. Our results showed that Hcy suppressed 
      rosiglitazone-induced adipogenesis in a similar fashion as this by insulin, 
      suggesting that inhibition of PPAR-gamma transactivation was critically involved 
      in the Hcy-induced inhibitory effect on adipogenesis. Taken together, our data 
      indicate that Hcy suppressed adipogenesis in 3T3-L1 preadipocytes and the 
      inhibition of PPAR-gamma transactivity may, at least partially, contribute to the 
      suppressive effect.
FAU - Wang, Zhigang
AU  - Wang Z
AD  - College of Pharmacy, Harbin Medical University, Harbin, Heilongjiang 150086, P R 
      China.
FAU - Dou, Xiaobing
AU  - Dou X
FAU - Yao, Tong
AU  - Yao T
FAU - Song, Zhenyuan
AU  - Song Z
LA  - eng
GR  - K01 AA015344/AA/NIAAA NIH HHS/United States
GR  - R01 AA017442/AA/NIAAA NIH HHS/United States
GR  - R01 AA017442-04/AA/NIAAA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20111123
PL  - Switzerland
TA  - Exp Biol Med (Maywood)
JT  - Experimental biology and medicine (Maywood, N.J.)
JID - 100973463
RN  - 0 (Fabp4 protein, mouse)
RN  - 0 (Fatty Acid-Binding Proteins)
RN  - 0 (PPAR gamma)
RN  - 0 (Retinoblastoma Protein)
RN  - 0LVT1QZ0BA (Homocysteine)
SB  - IM
MH  - Adipocytes/drug effects
MH  - Adipogenesis/*drug effects
MH  - Animals
MH  - Cell Differentiation
MH  - Fatty Acid-Binding Proteins/genetics
MH  - Gene Expression Regulation/drug effects
MH  - Homocysteine/*pharmacology
MH  - Lipid Metabolism/drug effects
MH  - Mice
MH  - NIH 3T3 Cells
MH  - PPAR gamma/genetics
MH  - Phosphorylation/drug effects
MH  - Retinoblastoma Protein/metabolism
PMC - PMC5534134
MID - NIHMS350697
EDAT- 2011/11/25 06:00
MHDA- 2012/02/03 06:00
PMCR- 2017/07/29
CRDT- 2011/11/25 06:00
PHST- 2011/11/25 06:00 [entrez]
PHST- 2011/11/25 06:00 [pubmed]
PHST- 2012/02/03 06:00 [medline]
PHST- 2017/07/29 00:00 [pmc-release]
AID - ebm.2011.011234 [pii]
AID - 10.1258/ebm.2011.011234 [doi]
PST - ppublish
SO  - Exp Biol Med (Maywood). 2011 Dec;236(12):1379-88. doi: 10.1258/ebm.2011.011234. 
      Epub 2011 Nov 23.