Activation of LKB1 rescues 3T3-L1 adipocytes from senescence induced by Sirt1 knock-down: a pivotal role of LKB1 in cellular aging

Previous reports have shown that excess calorie intake promotes p53 dependent senescence in mouse adipose tissues. The objective of the current study was to address the mechanism underlying this observation, i.e. adipocyte aging. Using cultured 3T3-L1 cells, we investigated the involvement of energy...

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Published in:Aging (Albany, NY.) NY.), 2020-10, Vol.12 (19), p.18942-18956
Main Authors: Lan, Fan, Lin, Yan, Gao, Zhenfeng, Cacicedo, Jose M, Weikel, Karen, Ido, Yasuo
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container_issue 19
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container_title Aging (Albany, NY.)
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creator Lan, Fan
Lin, Yan
Gao, Zhenfeng
Cacicedo, Jose M
Weikel, Karen
Ido, Yasuo
description Previous reports have shown that excess calorie intake promotes p53 dependent senescence in mouse adipose tissues. The objective of the current study was to address the mechanism underlying this observation, i.e. adipocyte aging. Using cultured 3T3-L1 cells, we investigated the involvement of energy regulators Sirt1, AMPK, and LKB1 in senescence. Fifteen days post differentiation, Sirt1 knock-down increased senescence-associated beta-galactosidase (SA-β-Gal) staining by 20-40% (p
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The objective of the current study was to address the mechanism underlying this observation, i.e. adipocyte aging. Using cultured 3T3-L1 cells, we investigated the involvement of energy regulators Sirt1, AMPK, and LKB1 in senescence. Fifteen days post differentiation, Sirt1 knock-down increased senescence-associated beta-galactosidase (SA-β-Gal) staining by 20-40% (p&lt;0.05, n=12) and both cyclin kinase inhibitor p21 and chemokine receptor IL8Rb expression by 2-4 fold. ATP and expression of mitochondria Complex 1 were also reduced by 30% and 50%, respectively (p&lt;0.05, n=4). Such energy depletion may have caused the observed increase in AMPK activity, despite LKB1 activity downregulation. This association between Sirt1 and LKB1 activity was confirmed in mouse adipose tissue. Upregulation of LKB1 activity by expression of the Sirt1-insensitive LKB1-K48R mutant in 3T3-L1 cells completely prevented the senescence-associated changes of Sirt1 knock-down. 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title Activation of LKB1 rescues 3T3-L1 adipocytes from senescence induced by Sirt1 knock-down: a pivotal role of LKB1 in cellular aging
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