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Suh, Pann-Ghill
BioSignal Network Lab (BSN)
Research Interests
  • Signal transduction, cancer, metabolism, phospholipase C

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SREBP-2/PNPLA8 axis improves non-alcoholic fatty liver disease through activation of autophagy

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Title
SREBP-2/PNPLA8 axis improves non-alcoholic fatty liver disease through activation of autophagy
Author
Kim, Kwang-Youn KimJang, Hyun-JunYang, Yong RyulPark, Kwang-IlSeo, Jeong KonShin, Il-WooJeon, Tae-IlAhn, Soon-cheolSuh, Pann-GhillOsborne, Timothy F.Seo, Young Kyo
Keywords
Pre-diabetes; Transcriptional regulatory elements
Issue Date
201610
Publisher
NATURE PUBLISHING GROUP
Citation
SCIENTIFIC REPORTS, v.6, no., pp.35732 -
Abstract
Dysregulated autophagy is associated with steatosis and non-alcoholic fatty liver disease (NAFLD), however the mechanisms connecting them remain poorly understand. Here, we show that co-administration of lovastatin and ezetimibe (L/E) significantly reverses hepatic triglyceride accumulation concomitant with an increase in SREBP-2 driven autophagy in mice fed a high-fat diet (HFD). We further show that the statin mediated increase in SREBP-2 directly activates expression of patatin-like phospholipase domain-containing enzyme 8 (PNPLA8) gene, and PNPLA8 associates with autophagosomes and is associated with a decrease in cellular triglyceride. Moreover, we show that over-expression of PNPLA8 dramatically decreases hepatic steatosis through increased autophagy in hepatocytes of HFD-fed mice. Live-cell imaging analyses also reveal that PNPLA8 dynamically interacts with LC3 and we suggest that the SREBP-2/PNPLA8 axis represents a novel regulatory mechanism for lipid homeostasis. These data provide a possible mechanism for the reported beneficial effects of statins for decreasing hepatic triglyceride levels in NAFLD patients.
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DOI
http://dx.doi.org/10.1038/srep35732
ISSN
2045-2322
Appears in Collections:
UCRF_Journal Papers
SLS_Journal Papers
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