Novel role of autophagy-associated Pik3c3 gene in gonadal white adipose tissue browning in aged C57/Bl6 male mice
Ghosh, AK; Mau, T; O'Brien, M; Yung, R
2018-04-01
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.Publisher
Impact Journals, LLC
ISSN
1945-4589 1945-4589
Deep Blue DOI
Other DOIs
PMID
29695642
Subjects
ER-Stress adipose tissue aging autophagy inflammation Adipose Tissue, Brown Adipose Tissue, White Adiposity Aging Animals Autophagy Class III Phosphatidylinositol 3-Kinases Endoplasmic Reticulum Stress Inflammation Male Mice Mice, Inbred C57BL Mice, Knockout
Types
Article
Metadata
Show full item recordCollections
Except where otherwise noted, this item's license is described as Licence for published version: Creative Commons Attribution 4.0 International
Showing items related by title, author, creator and subject.
-
Gao, Chuan; Langefeld, Carl D.; Ziegler, Julie T.; Taylor, Kent D.; Norris, Jill M.; Chen, Yii‐der I.; Hellwege, Jacklyn N.; Guo, Xiuqing; Allison, Matthew A.; Speliotes, Elizabeth K.; Rotter, Jerome I.; Bowden, Donald W.; Wagenknecht, Lynne E.; Palmer, Nicholette D. (Wiley Periodicals, Inc., 2018-01)
-
Morris, David L.; Oatmen, Kelsie E.; Mergian, Taleen A.; Cho, Kae Won; DelProposto, Jennifer L.; Singer, Kanakadurga; Evans‐molina, Carmella; O’rourke, Robert W.; Lumeng, Carey N. (Wiley Periodicals, Inc., 2016-06)
-
Zimmermann, E.; Ängquist, L. H.; Mirza, S. S.; Zhao, J. H.; Chasman, D. I.; Fischer, K.; Qi, Q.; Smith, A. V.; Thinggaard, M.; Jarczok, M. N.; Nalls, M. A.; Trompet, S.; Timpson, N. J.; Schmidt, B.; Jackson, A. U.; Lyytikäinen, L. P.; Verweij, N.; Mueller‐nurasyid, M.; Vikström, M.; Marques‐vidal, P.; Wong, A.; Meidtner, K.; Middelberg, R. P.; Strawbridge, R. J.; Christiansen, L.; Orho‐melander, M.; Kyvik, K. O.; Hamsten, A.; Jääskeläinen, T.; Tjønneland, A.; Eriksson, J. G.; Whitfield, J. B.; Boeing, H.; Hardy, R.; Vollenweider, P.; Leander, K.; Peters, A.; Harst, P.; Kumari, M.; Lehtimäki, T.; Meirhaeghe, A.; Tuomilehto, J.; Jöckel, K.‐h.; Ben‐shlomo, Y.; Sattar, N.; Baumeister, S. E.; Davey Smith, G.; Casas, J. P.; Houston, D. K.; März, W.; Christensen, K.; Gudnason, V.; Hu, F. B.; Metspalu, A.; Ridker, P. M.; Wareham, N. J.; Loos, R. J. F.; Tiemeier, H.; Sonestedt, E.; Sørensen, T. I. A. (John Wiley & Sons, Ltd, 2015-04)
Remediation of Harmful Language
The University of Michigan Library aims to describe library materials in a way that respects the people and communities who create, use, and are represented in our collections. Report harmful or offensive language in catalog records, finding aids, or elsewhere in our collections anonymously through our metadata feedback form. More information at Remediation of Harmful Language.
Accessibility
If you are unable to use this file in its current format, please select the Contact Us link and we can modify it to make it more accessible to you.