HIF-1-dependent lipin1 induction prevents excessive lipid accumulation in choline-deficient diet-induced fatty liver

Scientific Reports
Takatomo AraiNobuhito Goda

Abstract

Adaptive responses to hypoxia regulate hepatic lipid metabolism, but their consequences in nonalcoholic fatty liver disease (NAFLD) are largely unknown. Here, we show that hypoxia inducible factor-1 (HIF-1), a key determinant of hypoxic adaptations, prevents excessive hepatic lipid accumulation in the progression of NAFLD. When exposed to a choline-deficient diet (CDD) for 4 weeks, the loss of hepatic Hif-1α gene accelerated liver steatosis with enhanced triglyceride accumulation in the liver compared to wild-type (WT) livers. Expression of genes involved in peroxisomal fatty acid oxidation was suppressed significantly in CDD-treated WT livers, whereas this reduction was further enhanced in Hif-1α-deficient livers. A lack of induction and nuclear accumulation of lipin1, a key regulator of the PPARα/PGC-1α pathway, could be attributed to impaired peroxisomal β-oxidation in Hif-1α-deficient livers. The lipin1-mediated binding of PPARα to the acyl CoA oxidase promoter was markedly reduced in Hif-1α-deficient mice exposed to a CDD. Moreover, forced Lipin1 expression restored the aberrant lipid accumulation caused by Hif-1α deletion in cells incubated in a choline-deficient medium. These results strongly suggest that HIF-1 plays a c...Continue Reading

References

Feb 1, 1990·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Z M Yao, D E Vance
Apr 12, 2001·Seminars in Liver Disease·M S Rao, J K Reddy
Aug 30, 2008·The Biochemical Journal·Sudheer K MantenaShannon M Bailey
Jan 2, 2009·Cell Metabolism·Julián AragonésPeter Carmeliet
Mar 25, 2009·Proceedings of the National Academy of Sciences of the United States of America·Masashi OkamuraJuro Sakai
Aug 1, 2009·Biochemical and Biophysical Research Communications·Toshihide TajimaMakoto Suematsu
Aug 10, 2010·Biochimica Et Biophysica Acta·Maroun Bou KhalilZemin Yao
May 4, 2011·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Aijuan QuYatrik M Shah
Jul 30, 2011·Obesity·Luciano F DragerVsevolod Y Polotsky
Sep 8, 2011·Journal of Hepatology·Yasumasa NishiyamaMakoto Suematsu
Dec 17, 2011·Journal of Hepatology·Lars P BechmannAli Canbay
Apr 3, 2012·Journal of Cell Science·Ilias MylonisGeorge Simos
Sep 4, 2012·Journal of Hepatology·Tung-Ming Leung, Natalia Nieto
Jun 22, 2013·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Ming HuMin You

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Citations

Apr 18, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Xin ZhangPing Xie
Mar 6, 2019·Cells·Ilias MylonisEfrosyni Paraskeva
Sep 12, 2020·Cell Communication and Signaling : CCS·Emma BarrosoManuel Vázquez-Carrera
Sep 27, 2019·Frontiers in Molecular Biosciences·Susan F Fitzpatrick
Nov 17, 2020·Frontiers in Medicine·Stephania C IsazaCarmelo García-Monzón
Mar 16, 2021·Frontiers in Endocrinology·Panyisha WuNicholas J G Webster
Aug 8, 2021·Cells·Beatrice FogliaMaurizio Parola

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Methods Mentioned

BETA
ChIP
PCR
immunoprecipitation
confocal microscopy

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