An intervention study in obese mice with astaxanthin, a marine carotenoid--effects on insulin signaling and pro-inflammatory cytokines.

Astaxanthin (ASX), a xanthophyll carotenoid from the marine algae Hematococcus pluvialis, has anti-obesity and insulin-sensitivity effects. The specific molecular mechanisms of its actions are not yet established. The present study was designed to investigate the mechanisms underlying the insulin sensitivity effects of ASX in a non-genetic insulin resistant animal model. A group of male Swiss albino mice was divided into two and fed either a starch-based control diet or a high fat-high fructose diet (HFFD). Fifteen days later, mice in each dietary group were divided into two and were treated with either ASX (6 mg kg(-1) per day) in olive oil or olive oil alone. At the end of 60 days, glucose, insulin and pro-inflammatory cytokines in plasma, lipids and oxidative stress markers in skeletal muscle and adipose tissue were assessed. Further, post-receptor insulin signaling events in skeletal muscle were analyzed. Increased body weight, hyperglycemia, hyperinsulinemia and increased plasma levels of tumor necrosis factor-α and interleukin-6 observed in HFFD-fed mice were significantly improved by ASX addition. ASX treatment also reduced lipid levels and oxidative stress in skeletal muscle and adipose tissue. ASX improved insulin signaling by enhancing the autophosphorylation of insulin receptor-β (IR-β), IRS-1 associated PI3-kinase step, phospho-Akt/Akt ratio and GLUT-4 translocation in skeletal muscle. This study demonstrates for the first time that chronic ASX administration improves insulin sensitivity by activating the post-receptor insulin signaling and by reducing oxidative stress, lipid accumulation and proinflammatory cytokines in obese mice.