Fucoxanthin promotes translocation and induction of glucose transporter 4 in skeletal muscles of diabetic/obese KK-A mice

Abstract

Fucoxanthin (Fx) isolated from Undaria pinnatifida suppresses the development of hyperglycemia and hyperinsulinemia of diabetic/obese KK-A y mice after two weeks of feeding 0.2% Fx-containing diet. In the soleus muscle of KK-A y mice that were fed Fx, glucose transporter 4 (GLUT4) translocation to plasma membranes from cytosol was promoted. On the other hand, Fx increased GLUT4 expression levels in the extensor digitorum longus (EDL) muscle, although GLUT4 translocation tended to increase. The expression levels of insulin receptor (IR) mRNA and phosphorylation of Akt, which are in upstream of the insulin signaling pathway regulating GLUT4 translocation, were also enhanced in the soleus and EDL muscles of the mice fed Fx. Furthermore, Fx induced peroxisome proliferator activated receptor  coactivator-1 (PGC-1), which has been reported to increase GLUT4 expression, in both soleus and EDL muscles. These results suggest that in diabetic/obese KK-A y mice, Fx improves hyperglycemia by activating the insulin signaling pathway, including GLUT4 translocation, and inducing GLUT4 expression in the soleus and EDL muscles, respectively, of diabetic/obese KK-A y mice.

<i>In Vivo</i> Antioxidant Activity of Fucoxanthin on Obese/Diabetes KK-<i>A<sup>y</sup></i> Mice

“…Therefore, the in vivo antioxidant activity of fucoxanthin on KK-A y mice found in Figure 4 would be partly due to the significant reduction of blood glucose level. Anti-diabetic effect of fucoxanthin has been well studied at molecular level [21][22][23][24]. One of the molecular mechanisms is the regulatory effect of fucoxanthin metabolites accumulated in abdominal WAT on releasing biologically active mediators termed adipokines.…”

“…Fucoxanthin can quench 1 O 2 ; however the ability is lower than those of β-carotene, lycopene, and ataxanthin because of the lower number of conjugated double bonds present in the molecule. On the other hand, our previous studies shows that fucoxanthin improves insulin resistance and decreases blood glucose levels through down-regulation of several adipokines, up-regulation of glucose transporter 4 (GLUT4) expression in skeletal muscle, and promotion of GLUT4 translocation to the cell membrane [21][22][23][24]. This regulatory effect of fucoxanthin on target molecules would be main mechanism to explain its in vivo antioxidant activity.…”

Nutraceutical Effects of Fucoxanthin for Obesity and Diabetes Therapy: A Review

“…In this study, GLUT4 mRNA levels were restored in the fucoxanthin-containing diet group compared with control diet group. In KK-A y mice fed 0.2 fucoxanthin diets, GLUT4 translocation in skeletal muscle was recovered compared with that in control mice 22 . In addition, insulin receptor mRNA expression was up-regulated.…”

“…These findings demonstrate that fucoxanthin metabolite directly suppresses the production of pro-inflammatory adipocytokines. In addition to moderating inflammatory in adipocyte cells, fucoxanthin regulates glucose transporter 4 GLUT4 activities in muscle tissues 21,22 . Skeletal muscle accounts for nearly 40 of base metabolism, playing a noteworthy role in the insulin-induced stimulation of glucose uptake 23 .…”

Comparison of extraction methods for selected carotenoids from macroalgae and the assessment of their seasonal/spatial variation

“…Generally fucoxanthins are polygenic carotenoids with linear conjugated double bonds as observed for β-carotene ( Figure 1). Fucoxanthin is purported to have antioxidant (Sachindra et al, 2007;Airanthi et al, 2011;Fung et al, 2013), anti-inflammatory (Heo et al, 2008;Kim et al, 2010;Heo et al, 2012), anti-cancer (Miki, 1991;Miyashita et al, 2011), anti-obesity (Maeda et al, 2005;Gammone and D'Orazio, 2015), anti-diabetic Hosokawa et al, 2010;Nishikawa et al, 2012), hepatoprotective (Woo et al, 2010) and skin-protective effects (Heo and Jeon, 2009;Urikura et al, 2011). It therefore could be exploited for potential uses in both the pharmaceutical and food industries.…”