Insulin‐Sensitizing and Beneficial Lipid‐Metabolic Effects of the Water‐Soluble Melanin Complex Extracted from Inonotus obliquus

Inonotus obliquus has been traditionally used for treatment of metabolic diseases; however, the mechanism remains to be elucidated. In this study, we found that the water‐soluble melanin complex extracted from I. obliquus improved insulin sensitivity and reduced adiposity in high fat (HF)‐fed obese mice. When the melanin complex was treated to 3T3‐L1 adipocytes, insulin‐stimulated glucose uptake was increased significantly, and its phosphoinositide 3‐kinase‐dependent action was proven with wortmannin treatment. Additionally, dose‐dependent increases in Akt phosphorylation and glucose transporter 4 translocation into the plasma membrane were observed in melanin complex‐treated cells. Adiponectin gene expression in 3T3‐L1 cells incubated with melanin complex increased which was corroborated by increased AMP‐activated protein kinase phosphorylation in HepG2 and C2C12 cells treated with conditioned media from the 3T3‐L1 culture. Melanin complex‐treated 3T3‐L1 cells showed no significant change in expression of several lipogenic genes, whereas enhanced expressions of fatty acid oxidative genes were observed. Similarly, the epididymal adipose tissue of melanin complex‐treated HF‐fed mice had higher expression of fatty acid oxidative genes without significant change in lipogenic gene expression. Together, these results suggest that the water‐soluble melanin complex of I. obliquus exerts antihyperglycemic and beneficial lipid‐metabolic effects, making it a candidate for promising antidiabetic agent. Copyright © 2014 John Wiley & Sons, Ltd.