title: αMSH promotes preadipocyte proliferation by alleviating ER stress-induced leptin resistance and by activating Notch1 signal in mice.
abstract: Alpha-melanocyte stimulating hormone (αMSH) has an important role in the regulation of body weight and energy expenditure. Nevertheless, the molecular mechanisms of circulating αMSH on preadipocyte proliferation remain elusive. We found αMSH 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. αMSH increased leptin sensitivity and alleviated ER stress along with increased p-STAT3 level and reduced SOCS3, GRP78, CHOP, ATF4, p27 and p53 levels. αMSH 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. αMSH 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 αMSH and leptin were blocked by the specific inhibitor of Notch1 signal. In summary, our data revealed αMSH enhanced leptin sensitivity and preadipocyte proliferation, meanwhile inhibited ER stress of preadipocytes by activating Notch1 signal.
authors.affiliation: College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Gan
authors.affiliation: College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, China.
authors.forename: Zhenjiang
authors.initials: Z
authors.lastname: Liu
authors.affiliation: College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, China.
authors.forename: Tianjiao
authors.initials: T
authors.lastname: Wu
authors.affiliation: College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Feng
authors.affiliation: College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, China. Electronic address: sunchao2775@163.com.
authors.forename: Chao
authors.initials: C
authors.lastname: Sun
mesh_terms: D017667:Adipocytes / Q000166:cytology* / Q000378:metabolism; D000818:Animals; D002453:Cell Cycle; D049109:Cell Proliferation; D002478:Cells, Cultured; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress; D020738:Leptin / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D051881:Receptor, Notch1 / Q000378:metabolism*; D015398:Signal Transduction; D000521:alpha-MSH / Q000378:metabolism*
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; C000717248:Hspa5 protein, mouse; D020738:Leptin; C497762:Notch1 protein, mouse; D051881:Receptor, Notch1; D000521:alpha-MSH
keywords: Cell cycle; Endoplasmic reticulum stress; Leptin; Notch; αMSH