title: Obesity-induced endoplasmic reticulum stress suppresses nuclear factor-Y expression.
abstract: Nuclear transcription factor Y (NF-Y) is an evolutionarily conserved transcription factor composed of three subunits, NF-YA, NF-YB, and NF-YC. NF-Y plays crucial roles in pre-adipocyte maintenance and/or commitment to adipogenesis. NF-YA dysfunction in adipocyte resulted in an age-dependent progressive loss of adipose tissue associated with metabolic complications. Endoplasmic reticulum (ER) stress has emerged as an important mediator in the pathogenesis of obesity. However, it is not known if NF-YA is involved in the ER stress-mediated pathogenesis of obesity. We first examined the effects of ER stress on the NF-YA expression in cultured 3T3-L1 adipocytes; then in ob/ob genetic obesity mice, we tested the effect of chemical chaperones alleviating ER stress on the expression levels of NF-YA. Subsequently, we inhibited the new mRNA synthesis using actinomycin D in 3T3-L1 cells to explore the mechanism modulating NF-YA expression. Finally, we evaluated the involvement of PPARg in the regulation of NF-YA expression by ER stress. We demonstrated that both obesity- and chemical chaperone -induced ER stress suppressed NF-YA expression and alleviation of ER stress by chemical chaperone could recover NF-YA expression in ob/ob mice. Moreover, we showed that ER stress suppressed NF-YA mRNA transcription through the involvement of peroxisome proliferator-activated receptor gamma (PPARg). Activation of PPARg ameliorates the ER stress-induced NF-YA suppression. Our findings may point to a possible role of NF-YA in stress conditions that occur in chronic obesity, ER stress might be involved in the pathogenesis of obesity through NF-YA depletion.
authors.affiliation: Molecular Medicine Research Center, West China Hospital, and State Key Laboratory of Biotherapy, Sichuan University, 1 Keyuan 4th Road, Gaopeng Street, Chengdu, 610041, Sichuan, China.
authors.forename: Yulan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Division of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.
authors.forename: Yuwei
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Molecular Medicine Research Center, West China Hospital, and State Key Laboratory of Biotherapy, Sichuan University, 1 Keyuan 4th Road, Gaopeng Street, Chengdu, 610041, Sichuan, China.
authors.forename: Yanjie
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Molecular Medicine Research Center, West China Hospital, and State Key Laboratory of Biotherapy, Sichuan University, 1 Keyuan 4th Road, Gaopeng Street, Chengdu, 610041, Sichuan, China.
authors.forename: Jinlong
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Molecular Medicine Research Center, West China Hospital, and State Key Laboratory of Biotherapy, Sichuan University, 1 Keyuan 4th Road, Gaopeng Street, Chengdu, 610041, Sichuan, China.
authors.forename: Yin
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Molecular Medicine Research Center, West China Hospital, and State Key Laboratory of Biotherapy, Sichuan University, 1 Keyuan 4th Road, Gaopeng Street, Chengdu, 610041, Sichuan, China.
authors.forename: Peiqun
authors.initials: P
authors.lastname: Feng
authors.affiliation: Molecular Medicine Research Center, West China Hospital, and State Key Laboratory of Biotherapy, Sichuan University, 1 Keyuan 4th Road, Gaopeng Street, Chengdu, 610041, Sichuan, China. zhiguang.su@scu.edu.cn.
authors.forename: Zhiguang
authors.initials: Z
authors.lastname: Su
mesh_terms: D041721:3T3-L1 Cells; D000818:Animals; D023081:CCAAT-Binding Factor / Q000096:biosynthesis* / Q000235:genetics; D059865:Endoplasmic Reticulum Stress; D005786:Gene Expression Regulation; D008297:Male; D051379:Mice; D008820:Mice, Obese; D009765:Obesity / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism
chemical_list: D023081:CCAAT-Binding Factor; C492060:Nfya protein, mouse; D047495:PPAR gamma
keywords: Adipocyte; ER stress; NF-Y; Obese; PPARg; Transcriptional regulation