Novel role of autophagy-associated Pik3c3 gene in gonadal white adipose tissue browning in aged C57/Bl6 male mice
dc.contributor.author | Ghosh, AK | |
dc.contributor.author | Mau, T | |
dc.contributor.author | O'Brien, M | |
dc.contributor.author | Yung, R | |
dc.coverage.spatial | United States | |
dc.date.accessioned | 2024-05-06T19:05:37Z | |
dc.date.available | 2024-05-06T19:05:37Z | |
dc.date.issued | 2018-04-01 | |
dc.identifier.issn | 1945-4589 | |
dc.identifier.issn | 1945-4589 | |
dc.identifier.uri | https://www.ncbi.nlm.nih.gov/pubmed/29695642 | |
dc.identifier.uri | https://hdl.handle.net/2027.42/193084 | en |
dc.description.abstract | Adipose tissue dysfunction is associated with inflammation, metabolic syndrome and other diseases in aging. Recent work has demonstrated that compromised autophagy activity in aging adipose tissue promotes ER stress responses, contributing to adipose tissue and systemic inflammation in aging. Phosphatidylinositol 3- kinase catalytic subunit type 3 (Pik3c3) is an 887 amino acid lipid kinase that regulates intracellular membrane trafficking and autophagy activity. To address the mechanistic link between autophagy and ER stress response in aging adipose tissue, we generated a line of adipose tissue-specific Pik3c3 knock out (~mutant mice) with the Fabp4 (Fatty acid binding protein 4) promoter driven Cre recombinase system. We found elevated ER stress response signaling with reduced autophagy activity without any significant change on adiposity or glucose tolerance in early life of Pik3c3 mutant mice. Interestingly, middle- and old-aged mutant mice exhibited improved glucose tolerance (GTT) and reduced adiposity compared to age and sex-matched littermates. In addition, adipose tissue-specific Pik3c3 mutants display reduced expression of adiposity-associated genes with the signature of adipose tissue browning phenotypes in old age. Overall, the results suggest that altered adipose tissue characteristics due to autophagy inhibition early in life has beneficial effects that promote adipose tissue browning and improves glucose tolerance in late-life. | |
dc.format.medium | ||
dc.language | eng | |
dc.publisher | Impact Journals, LLC | |
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 | Adipose Tissue, Brown | |
dc.subject | Adipose Tissue, White | |
dc.subject | Adiposity | |
dc.subject | Aging | |
dc.subject | Animals | |
dc.subject | Autophagy | |
dc.subject | Class III Phosphatidylinositol 3-Kinases | |
dc.subject | Endoplasmic Reticulum Stress | |
dc.subject | Inflammation | |
dc.subject | Male | |
dc.subject | Mice | |
dc.subject | Mice, Inbred C57BL | |
dc.subject | Mice, Knockout | |
dc.title | Novel role of autophagy-associated Pik3c3 gene in gonadal white adipose tissue browning in aged C57/Bl6 male mice | |
dc.type | Article | |
dc.identifier.pmid | 29695642 | |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/193084/2/aging-10-101426.pdf | |
dc.identifier.doi | 10.18632/aging.101426 | |
dc.identifier.doi | https://dx.doi.org/10.7302/22729 | |
dc.identifier.source | Aging | |
dc.description.version | Published version | |
dc.date.updated | 2024-05-06T19:05:36Z | |
dc.identifier.orcid | 0000-0002-8181-027X | |
dc.identifier.volume | 10 | |
dc.identifier.issue | 4 | |
dc.identifier.startpage | 764 | |
dc.identifier.endpage | 774 | |
dc.identifier.name-orcid | Ghosh, AK | |
dc.identifier.name-orcid | Mau, T | |
dc.identifier.name-orcid | O'Brien, M | |
dc.identifier.name-orcid | Yung, R; 0000-0002-8181-027X | |
dc.working.doi | 10.7302/22729 | en |
dc.owningcollname | Internal Medicine, Department of |
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