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Abstract Title:

The natural carotenoid astaxanthin, a PPAR-α agonist and PPAR-γ antagonist, reduces hepatic lipid accumulation by rewiring the transcriptome in lipid-loaded hepatocytes.

Abstract Source:

Mol Nutr Food Res. 2012 Jun ;56(6):878-88. PMID: 22707263

Abstract Author(s):

Yaoyao Jia, Jin-Young Kim, Hee-Jin Jun, Sun-Joong Kim, Ji-Hae Lee, Minh Hien Hoang, Kwang-Yeon Hwang, Soo-Jong Um, Hyo Ihl Chang, Sung-Joon Lee

Article Affiliation:

Department of Biotechnology, Graduate School of Biotechnology, Korea University, Seoul, Republic of Korea; Division of Food Bioscience and Technology, College of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea.

Abstract:

SCOPE: A natural carotenoid abundant in seafood, astaxanthin (AX), has hypolipidemic activity, but its underlying mechanisms of action and protein targets are unknown. We investigated the molecular mechanism of action of AX in hepatic hyperlipidemia by measuring peroxisome proliferator-activated receptors (PPAR) activity.

METHODS AND RESULTS: We examined the binding of AX to PPAR subtypes and its effects on hepatic lipid metabolism. AX binding activated PPAR-α, but inhibited PPAR-γ transactivation activity in reporter gene assay and time-resolved fluorescence energy transfer analyses. AX had no effect on PPARδ/β transactivation. AX bound directly to PPAR-α and PPAR-γ with moderate affinity, as assessed by surface plasmon resonance experiments. Thedifferential effects of AX on PPARs were confirmed by measuring the expression of unique responsive genes for each PPAR subtype. AX significantly reduced cellular lipid accumulation in lipid-loaded hepatocytes. Transcriptome analysis revealed that the net effects of stimulation with AX (100 μM) onlipid metabolic pathways were similar to those elicited by fenofibrate and lovastatin (10 μM each), with AX rewiring the expression of genes involved in lipid metabolic pathways.

CONCLUSION: AX is a PPAR-α agonist and PPAR-γ antagonist, reduces hepatic lipid accumulation by rewiring the transcriptome in lipid-loaded hepatocytes.

Study Type : In Vitro Study
Additional Links
Pharmacological Actions : Hepatoprotective

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