Novel role of autophagy-associated Pik3c3 gene in gonadal white adipose tissue browning in aged C57/Bl6 male mice

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. Phosph...

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Bibliographic Details
Published in:Aging (Albany, NY.) NY.), 2018-04, Vol.10 (4), p.764-774
Main Authors: Ghosh, Amiya Kumar, Mau, Theresa, O'Brien, Martin, Yung, Raymond
Format: Article
Language:English
Subjects:
Adipose Tissue, Brown - metabolism
Adipose Tissue, Brown - pathology
Adipose Tissue, White - metabolism
Adipose Tissue, White - pathology
Adiposity - physiology
Aging - pathology
Animals
Autophagy - physiology
Class III Phosphatidylinositol 3-Kinases - genetics
Endoplasmic Reticulum Stress - genetics
Inflammation - genetics
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Research Paper
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Summary: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 knock out (~mutant mice) with the (Fatty acid binding protein 4) promoter driven 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 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.
ISSN:1945-4589
1945-4589
DOI:10.18632/aging.101426