Brown Remodeling of White Adipose Tissue by SirT1-Dependent Deacetylation of Pparγ
By L. Qiang, Liheng Wang, N. Kon, Wenhui Zhao, Sangkyu Lee, Yiying Zhang, M. Rosenbaum, Yingming Zhao, W. Gu, S. Farmer and 1 more. Cell, 2012
792 citations recorded by the source corpus.
SUMMARY Brown adipose tissue (BAT) can disperse stored energy as heat. Promoting BAT-like features in white adipose (WAT) is an attractive, if elusive therapeutic approach to staunch the current obesity epidemic. Here we report that gain-of-function of the NAD-dependent deacetylase SirT1 or loss-of-function of its endogenous inhibitor Deleted in breast cancer-1 (Dbc1) promote “browning” of WAT by deacetylating peroxisome proliferator-activated receptor (Ppar)-γ on Lys268 and Lys293. SirT1-dependent deacetylation of Lys268 and Lys293 is required to recruit the BAT program coactivator Prdm16 to Pparγ, leading to selective induction of BAT genes and repression of visceral WAT genes associated with insulin resistance. An acetylation-defective Pparγ mutant induces a brown phenotype in white adipocytes, while an acetylated mimetic fails to induce “brown” genes, but retains the ability to activate “white” genes. We propose that SirT1-dependent Pparγ deacetylation is a form of selective Pparγ modulation of potential therapeutic import.
Subfields: Cardiology and Cardiovascular Medicine, Geriatrics and Gerontology, Physiology
View Paper: https://www.semanticscholar.org/paper/c7acd4075f5ab4d3f13a2d50633f5e8d4e7303c9
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In Cardiology and Cardiovascular Medicine
In Geriatrics and Gerontology
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Citations in the corpus
- Adaptive thermogenesis in adipocytes: is beige the new brown? (2013, background): “Agonist treatment was shown to lead to deacetylation of PPARg, which is dependent on the NADdependent deacetylase SirT1 (Qiang et al. 2012).”
- SIRT1 and other sirtuins in Metabolism (2013, background): “Further, SIRT1 can induce white fat to switch into metabolically active brown fat by deacetylating two critical lysine residues on PPARγ (Figure 1) [84].”
- Brown and beige fat: Physiological roles beyond heat-generation (2015, background): “Additionally, a number of synthetic agonists or inhibitors, such as the PPARg agonists (Ohno et al., 2012; Petrovic et al., 2010; Qiang et al., 2012), FXR agonist fexaramine (Fang et al., 2015), soluble guanylyl cyclase (Hoffmann et al., 2015), GLP-1 agonist (Beiroa et al., 2014), Notch inhibitor…”