| First Author | Haj-Yasein NN | Year | 2017 |
| Journal | Biochim Biophys Acta | Volume | 1862 |
| Issue | 6 | Pages | 623-635 |
| PubMed ID | 28219719 | Mgi Jnum | J:250984 |
| Mgi Id | MGI:6105506 | Doi | 10.1016/j.bbalip.2017.02.009 |
| Citation | Haj-Yasein NN, et al. (2017) Cysteine deprivation prevents induction of peroxisome proliferator-activated receptor gamma-2 and adipose differentiation of 3T3-L1 cells. Biochim Biophys Acta 1862(6):623-635 |
| abstractText | Plasma cysteine is strongly associated with body fat mass in human cohorts and diets low in cysteine prevents fat accumulation in mice. It is unclear if plasma cysteine affects fat development or if fat accumulation raises plasma cysteine. To determine if cysteine affects adipogenesis, we differentiated 3T3-L1 preadipocytes in medium with reduced cysteine. Cells incubated in media with 10-20muM cysteine exhibited reduced capacity to differentiate into triacylglycerol-storing mature adipocytes compared with cells incubated with 50muM cysteine. Low cysteine severely reduced expression of peroxisome proliferator-activated receptor gamma2 (Ppargamma2) and its target genes perlipin1 (Plin1) and fatty acid binding protein-4 (Fabp4). Expression of stearoyl-CoA desaturase-1 (Scd1), known to be repressed with cysteine depletion, was also reduced with low cysteine. Medium depletion of the essential amino acids leucine, valine, and isoleucine had only a modest effect on adipocyte specific gene expression and differentiation. Stimulation with the PPARgamma agonist BRL-49653 or addition of a hydrogen sulfide donor enhanced differentiation of 3T3-L1 cells cultured in low cysteine. This demonstrates that the ability to induce PPARgamma expression is preserved when cells are cultured in low cysteine. It therefore appears that cysteine depletion inhibits adipogenesis by specifically affecting molecular pathways required for induction of PPARgamma expression, rather than through a general reduction of global protein synthesis. In conclusion, we show that low extracellular cysteine reduces adipocyte differentiation by interfering with PPARgamma2 and PPARgamma target gene expression. Our results provide further evidence for the hypothesis that plasma cysteine is a casual determinant for body fat mass. |
