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.

Carotenoids in the treatment of diabetes mellitus and its complications: A mechanistic review

“…Bhuvaneswari et al evaluated the effect of astaxanthin on NFkB-mediated inflammation in the liver of HFFD-fed mice. HFFD feeding increased p-IKKb and nuclear translocation of NF-kB while astaxanthin treatment inhibited IKKb phosphorylation and nuclear translocation of NF-kB p65 subunit [17]. The same results were reported in the proximal tubular epithelial cells.…”

“…These effects of astaxanthin have been attributed to its protective antioxidant effects on the pancreatic beta cells [16]. Such antidiabetic effects were also reported by Bhuvaneswari et al, in high fat plus HFFD-fed mice [17]. The effect of astaxanthin on metabolic syndrome in an experimental model of rats has also been evaluated.…”

“…The antioxidant effect of astaxanthin in HFFD-fed mice has been reported with significant protective effects [17]. It was demonstrated that in the liver of HFFD-fed mice, ROS production and endoplasmic reticulum stress markers including Ig-binding protein, PKR-like ER kinase, Xbox binding protein 1, activating transcription factor 6, phosphorylated eukaryotic initiation factor 2a, and the apoptotic marker caspase 12 were elevated and astaxanthin significantly normalized these changes [17]. As mentioned previously, neutrophils are another source of ROS production during hyperglycemia.…”

Alcohol stress, membranes, and chaperones

“…Astaxanthin, a carotenoid of marine animals, is also a powerful antioxidant. It has been shown to decrease the high fructose-fat diet induced ROS production and endoplasmatic reticulum stress in the liver (Bhuvaneswari et al 2013). Astaxanthin also antagonizes the ethanol effect on cortical spreading depression in the young adult rat brain (Abadie-Guedes et al 2008).…”

The antioxidant effect of astaxanthin is higher in young mice than aged: a region specific study on brain

“…It was dissolved in distilled water at a concentration of 2 mg/20 ml and administered orally at a dose of 2 mg/kg; (Bhuvaneswari et al 2014). The test sample was administered at single doses (2 mg/kg; per oral) for 4 weeks.…”