Obesity-induced endoplasmic reticulum stress suppresses nuclear factor-Y expression.

Publisher: Springer Country of Publication: Netherlands NLM ID: 0364456 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1573-4919 (Electronic) Linking ISSN: 03008177 NLM ISO Abbreviation: Mol Cell Biochem Subsets: MEDLINE

Publication: New York : Springer
Original Publication: The Hague, Dr. W. Junk B. V. Publishers.

Endoplasmic Reticulum Stress* ; Gene Expression Regulation*; CCAAT-Binding Factor/*biosynthesis ; Obesity/*metabolism; 3T3-L1 Cells ; Animals ; CCAAT-Binding Factor/genetics ; Male ; Mice ; Mice, Obese ; Obesity/genetics ; Obesity/pathology ; PPAR gamma/genetics ; PPAR gamma/metabolism

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.

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Keywords: Adipocyte; ER stress; NF-Y; Obese; PPARg; Transcriptional regulation

0 (CCAAT-Binding Factor)
0 (Nfya protein, mouse)
0 (PPAR gamma)

Date Created: 20161113 Date Completed: 20170217 Latest Revision: 20181113

20221213

10.1007/s11010-016-2879-7

27837431