title: Astaxanthin reduces hepatic endoplasmic reticulum stress and nuclear factor-κB-mediated inflammation in high fructose and high fat diet-fed mice.
abstract: We recently showed that astaxanthin (ASX), a xanthophyll carotenoid, activates phosphatidylinositol 3-kinase pathway of insulin signaling and improves glucose metabolism in liver of high fructose-fat diet (HFFD)-fed mice. The aim of this study is to investigate whether ASX influences phosphorylation of c-Jun-N-terminal kinase 1 (JNK1), reactive oxygen species (ROS) production, endoplasmic reticulum (ER) stress, and inflammation in liver of HFFD-fed mice. Adult male Mus musculus mice were fed either with control diet or HFFD for 15 days. After this period, mice in each group were divided into two and administered ASX (2 mg/kg/day, p.o) in 0.3 ml olive oil or 0.3 ml olive oil alone for the next 45 days. At the end of 60 days, liver tissue was excised and examined for lipid accumulation (Oil red O staining), intracellular ROS production, ER stress, and inflammatory markers. Elevated ROS production, lipid accumulation, and increased hepatic expression of ER stress markers such as Ig-binding protein, PKR-like ER kinase, phosphorylated eukaryotic initiation factor 2α, X-box binding protein 1, activating transcription factor 6, and the apoptotic marker caspase 12 were observed in the liver of the HFFD group. ASX significantly reversed these changes. This reduction was accompanied by reduced activation of JNK1 and I kappa B kinase β phosphorylation and nuclear factor-kappa B p65 nuclear translocation in ASX-treated HFFD mice. These findings suggest that alleviation of inflammation and ER stress by ASX could be a mechanism responsible for its beneficial effect in this model. ASX could be a promising treatment strategy for insulin resistant patients.
authors.affiliation: Department of Biochemistry and Biotechnology, Annamalai University, Annamalai Nagar, 608 002, Tamil Nadu, India.
authors.forename: Saravanan
authors.initials: S
authors.lastname: Bhuvaneswari
authors.forename: Baskaran
authors.initials: B
authors.lastname: Yogalakshmi
authors.forename: S
authors.initials: S
authors.lastname: Sreeja
authors.forename: Carani Venkatraman
authors.initials: CV
authors.lastname: Anuradha
mesh_terms: D000818:Animals; D001391:Azo Compounds / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D059305:Diet, High-Fat; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D005629:Frozen Sections; D005632:Fructose / Q000008:administration & dosage*; D051550:I-kappa B Kinase / Q000378:metabolism; D007249:Inflammation / Q000473:pathology*; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D013194:Staining and Labeling; D024341:Xanthophylls / Q000494:pharmacology
chemical_list: D001391:Azo Compounds; D015415:Biomarkers; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D024341:Xanthophylls; D005632:Fructose; C005948:astaxanthine; D051550:I-kappa B Kinase; D048031:JNK Mitogen-Activated Protein Kinases; C011049:oil red O