Elevated Endoplasmic Reticulum Stress Response Contributes to Adipose Tissue Inflammation in Aging
Ghosh, AK; Garg, SK; Mau, T; O'Brien, M; Liu, J; Yung, R
2015-11-01
Abstract
Adipose tissue inflammation has been linked to age-related metabolic diseases. However, the underlying mechanisms are poorly understood. Adipose tissue inflammation and insulin resistance in diet associated obesity has been correlated with aberrant endoplasmic reticulum (ER) stress. This study was undertaken to test our hypothesis that increased ER stress response contributes to age-associated adipose tissue inflammation. We found elevated ER stress response in adipose tissue of old (18-20 months) compared to young (4-6 months) mice. Elevated ER stress markers BIP (GRP78), CHOP, cleaved-ATF-6, phospho-IRE1α, and XBP-1 were observed in old compared to young adipose tissue stromal cells. Additionally, old adipose tissue stromal cells were more sensitive to an ER stress inducer, thapsigargin. Similar experiments with adipose tissue macrophages showed elevated Chop and Bip expression in old adipose tissue macrophages when induced with thapsigargin. Treatment of chemical chaperone 4-phenyle-butyric acid alleviated ER stress in adipose tissue stromal cells and adipose tissue macrophages and attenuated the production of IL-6 and MCP-1 by adipose tissue stromal cells, and TNF-α by adipose tissue macrophages from both young and old mice. Finally, old mice fed with 4-phenyle-butyric acid have reduced expression of ER stress and inflammatory cytokine genes. Our data suggests that an exaggerated ER stress response in aging adipose tissue contributes to age-associated inflammation that can be mitigated by treatment with chemical chaperones.Publisher
Oxford University Press (OUP)
ISSN
1079-5006 1758-535X
Deep Blue DOI
Other DOIs
PMID
25324219
Subjects
Adipose tissue Aging Chemical chaperones. ER stress response Activating Transcription Factor 6 Adipose Tissue Age Factors Animals Cell Culture Techniques Cytokines DNA-Binding Proteins Endoplasmic Reticulum Chaperone BiP Endoplasmic Reticulum Stress Endoribonucleases Enzyme Inhibitors Heat-Shock Proteins Inflammation Macrophages Male Mice Phenylbutyrates Protein Serine-Threonine Kinases RNA, Messenger Regulatory Factor X Transcription Factors Stromal Cells Thapsigargin Transcription Factor CHOP Transcription Factors X-Box Binding Protein 1
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