Abstract：
:Long non-coding RNAs (lncRNAs) constitute a significant portion of mammalian genome, yet the physiological importance of lncRNAs is largely unknown. Here, we identify a liver-enriched lncRNA in mouse that we term liver-specific triglyceride regulator (lncLSTR). Mice with a liver-specific depletion of lncLSTR exhibit a marked reduction in plasma triglyceride levels. We show that lncLSTR depletion enhances apoC2 expression, leading to robust lipoprotein lipase activation and increased plasma triglyceride clearance. We further demonstrate that the regulation of apoC2 expression occurs through an FXR-mediated pathway. LncLSTR forms a molecular complex with TDP-43 to regulate expression of Cyp8b1, a key enzyme in the bile acid synthesis pathway, and engenders an in vivo bile pool that induces apoC2 expression through FXR. Finally, we demonstrate that lncLSTR depletion can reduce triglyceride levels in a hyperlipidemia mouse model. Taken together, these data support a model in which lncLSTR regulates a TDP-43/FXR/apoC2-dependent pathway to maintain systemic lipid homeostasis.
journal_name
Cell Metabjournal_title
Cell metabolismauthors
Li P,Ruan X,Yang L,Kiesewetter K,Zhao Y,Luo H,Chen Y,Gucek M,Zhu J,Cao Hdoi
10.1016/j.cmet.2015.02.004subject
Has Abstractpub_date
2015-03-03 00:00:00pages
455-67issue
3eissn
1550-4131issn
1932-7420pii
S1550-4131(15)00056-Xjournal_volume
21pub_type
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