| First Author | Gan L | Year | 2017 |
| Journal | Biochim Biophys Acta | Volume | 1863 |
| Issue | 1 | Pages | 231-238 |
| PubMed ID | 27717825 | Mgi Jnum | J:256242 |
| Mgi Id | MGI:6105677 | Doi | 10.1016/j.bbadis.2016.10.001 |
| Citation | Gan L, et al. (2017) alphaMSH promotes preadipocyte proliferation by alleviating ER stress-induced leptin resistance and by activating Notch1 signal in mice. Biochim Biophys Acta 1863(1):231-238 |
| abstractText | Alpha-melanocyte stimulating hormone (alphaMSH) has an important role in the regulation of body weight and energy expenditure. Nevertheless, the molecular mechanisms of circulating alphaMSH on preadipocyte proliferation remain elusive. We found alphaMSH was reduced by high fat diet (HFD) while leptin was elevated in adipose tissue. Leptin resistance and endoplasmic reticulum (ER) stress of adipose tissue were increased in obese mice. alphaMSH increased leptin sensitivity and alleviated ER stress along with increased p-STAT3 level and reduced SOCS3, GRP78, CHOP, ATF4, p27 and p53 levels. alphaMSH and leptin co-treatment alleviated ER stress through decreasing the levels of GRP78 and CHOP. Tunicamycin (TM) or thapsigargin (Tg) induced ER stress blunted leptin sensitivity and inhibited preadipocyte proliferation. alphaMSH and leptin co-treatment increased the cell number, augmented G1-S transition, elevated leptin sensitivity, and reduced ER stress; it also activated Notch1 signal and stimulated preadipocyte proliferation, whereas ER stress marker genes were decreased during this process. However, the effects of alphaMSH and leptin were blocked by the specific inhibitor of Notch1 signal. In summary, our data revealed alphaMSH enhanced leptin sensitivity and preadipocyte proliferation, meanwhile inhibited ER stress of preadipocytes by activating Notch1 signal. |
