Abstract：
:Obesity and atherosclerosis-related diseases account for over one-third of deaths in the western world. Controlling these conditions remains a major challenge due to an incomplete understanding of the molecular pathways involved. Here, we show that Wip1 phosphatase, a known negative regulator of Atm-dependent signaling, plays a major role in controlling fat accumulation and atherosclerosis in mice; specifically, Wip1 deficiency prevents both conditions. In the course of atherosclerosis, deletion of Wip1 results in suppression of macrophage conversion into foam cells, thus preventing the formation of atherosclerotic plaques. This process appears to be independent of p53 but rely on a noncanonical Atm-mTOR signaling pathway and on selective autophagy in regulation of cholesterol efflux. We propose that the Wip1-dependent control of autophagy and cholesterol efflux may provide avenues for treating obesity and atherosclerosis.
journal_name
Cell Metabjournal_title
Cell metabolismauthors
Le Guezennec X,Brichkina A,Huang YF,Kostromina E,Han W,Bulavin DVdoi
10.1016/j.cmet.2012.06.003subject
Has Abstractpub_date
2012-07-03 00:00:00pages
68-80issue
1eissn
1550-4131issn
1932-7420pii
S1550-4131(12)00240-9journal_volume
16pub_type
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