Impaired autophagy activity is linked to elevated ER-stress and inflammation in aging adipose tissue
dc.contributor.author | Ghosh, AK | |
dc.contributor.author | Mau, T | |
dc.contributor.author | O'Brien, M | |
dc.contributor.author | Garg, S | |
dc.contributor.author | Yung, R | |
dc.coverage.spatial | United States | |
dc.date.accessioned | 2024-05-06T19:19:36Z | |
dc.date.available | 2024-05-06T19:19:36Z | |
dc.date.issued | 2016-01-01 | |
dc.identifier.issn | 1945-4589 | |
dc.identifier.issn | 1945-4589 | |
dc.identifier.uri | https://www.ncbi.nlm.nih.gov/pubmed/27777379 | |
dc.identifier.uri | https://hdl.handle.net/2027.42/193092 | en |
dc.description.abstract | Adipose tissue dysfunction in aging is associated with inflammation, metabolic syndrome and other diseases. We propose that impaired protein homeostasis due to compromised lysosomal degradation (micro-autophagy) might promote aberrant ER stress response and inflammation in aging adipose tissue. Using C57BL/6 mouse model, we demonstrate that adipose tissue-derived stromal vascular fraction (SVF) cells from old (18-20 months) mice have reduced expression of autophagy markers as compared to the younger (4-6 months) cohort. Elevated expressions of ER-stress marker CHOP and autophagy substrate SQSTM1/p62 are observed in old SVFs compared to young, when treated with either vehicle or with thapsigargin (Tg), an ER stress inducer. Treatment with bafilomycin A1 (Baf), a vacuolar-type H (+)-ATPase, or Tg elevated expressions of CHOP, and SQSTM1/p62 and LC-3-II, in 3T3-L1-preadipocytes. We also demonstrate impaired autophagy activity in old SVFs by analyzing increased accumulation of autophagy substrates LC3-II and p62. Compromised autophagy activity in old SVFs is correlated with enhanced release of pro-inflammatory cytokines IL-6 and MCP-1. Finally, SVFs from calorie restricted old mice (CR-O) have shown enhanced autophagy activity compared to ad libitum fed old mice (ALO). Our results support the notion that diminished autophagy activity with aging contributes to increased adipose tissue ER stress and inflammation. | |
dc.format.medium | ||
dc.language | eng | |
dc.publisher | Impact Journals | |
dc.rights | Licence for published version: Creative Commons Attribution 4.0 International | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.subject | ER-Stress | |
dc.subject | adipose tissue | |
dc.subject | aging | |
dc.subject | autophagy | |
dc.subject | inflammation | |
dc.subject | Adipocytes | |
dc.subject | Adipose Tissue | |
dc.subject | Aging | |
dc.subject | Animals | |
dc.subject | Autophagy | |
dc.subject | Chemokine CCL2 | |
dc.subject | Endoplasmic Reticulum Stress | |
dc.subject | Enzyme Inhibitors | |
dc.subject | Inflammation | |
dc.subject | Interleukin-6 | |
dc.subject | Lysosomes | |
dc.subject | Mice | |
dc.subject | Mice, Inbred C57BL | |
dc.subject | Thapsigargin | |
dc.title | Impaired autophagy activity is linked to elevated ER-stress and inflammation in aging adipose tissue | |
dc.type | Article | |
dc.identifier.pmid | 27777379 | |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/193092/2/aging-08-2525.pdf | |
dc.identifier.doi | 10.18632/aging.101083 | |
dc.identifier.doi | https://dx.doi.org/10.7302/22737 | |
dc.identifier.source | Aging | |
dc.description.version | Published version | |
dc.date.updated | 2024-05-06T19:19:34Z | |
dc.identifier.orcid | 0000-0002-8181-027X | |
dc.identifier.volume | 8 | |
dc.identifier.issue | 10 | |
dc.identifier.startpage | 2525 | |
dc.identifier.endpage | 2537 | |
dc.identifier.name-orcid | Ghosh, AK | |
dc.identifier.name-orcid | Mau, T | |
dc.identifier.name-orcid | O'Brien, M | |
dc.identifier.name-orcid | Garg, S | |
dc.identifier.name-orcid | Yung, R; 0000-0002-8181-027X | |
dc.working.doi | 10.7302/22737 | en |
dc.owningcollname | Internal Medicine, Department of |
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