Astaxanthin reduces hepatic lipid accumulations in high-fat-fed C57BL/6J mice via activation of peroxisome proliferator-activated receptor (PPAR) alpha and inhibition of PPAR gamma and Akt

Yaoyao Jia, Chunyan Wu, Jiyoung Kim, Bobae Kim, Sung-Joon Lee

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

We have previously reported that astaxanthin (AX), a dietary carotenoid, directly interacts with peroxisome proliferator-activated receptors PPARα and PPARγ, activating PPARα while inhibiting PPARγ, and thus reduces lipid accumulation in hepatocytes in vitro. To investigate the effects of AX in vivo, high-fat diet (HFD)-fed C57BL/6J mice were orally administered AX (or 30 mg/kg body weight) or vehicle for 8 weeks. AX significantly reduced the levels of triglyceride both in plasma and in liver compared with the control HFD mice. AX significantly improved liver histology and thus reduced both steatosis and inflammation scores of livers with hematoxylin and eosin staining. The number of inflammatory macrophages and Kupffer cells were reduced in livers by AX administration assessed with F4/80 staining. Hepatic PPARα-responsive genes involved in fatty acid uptake and β-oxidation were upregulated, whereas inflammatory genes were downregulated by AX administration. In vitro radiolabeled assays revealed that hepatic fatty acid oxidation was induced by AX administration, whereas fatty acid synthesis was not changed in hepatocytes. In mechanism studies, AX inhibited Akt activity and thus decreased SREBP1 phosphorylation and induced Insig-2a expression, both of which delayed nuclear translocation of SREBP1 and subsequent hepatic lipogenesis. Additionally, inhibition of the Akt-mTORC1 signaling axis by AX stimulated hepatic autophagy that could promote degradation of lipid droplets. These suggest that AX lowers hepatic lipid accumulation in HFD-fed mice via multiple mechanisms. In addition to the previously reported differential regulation of PPARα and PPARγ, inhibition of Akt activity and activation of hepatic autophagy reduced hepatic steatosis in mouse livers.

Original languageEnglish
Pages (from-to)9-18
Number of pages10
JournalJournal of Nutritional Biochemistry
Volume28
DOIs
Publication statusPublished - 2016 Feb 1

Keywords

  • Akt
  • Astaxanthin
  • Autophagy
  • PPAR
  • SREBP1

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Molecular Biology
  • Endocrinology, Diabetes and Metabolism
  • Nutrition and Dietetics

Fingerprint Dive into the research topics of 'Astaxanthin reduces hepatic lipid accumulations in high-fat-fed C57BL/6J mice via activation of peroxisome proliferator-activated receptor (PPAR) alpha and inhibition of PPAR gamma and Akt'. Together they form a unique fingerprint.

  • Cite this