Ternatin, a cyclic peptide isolated from mushroom, and its derivative suppress hyperglycemia and hepatic fatty acid synthesis in spontaneously diabetic KK-Ay mice

Abstract

(−)-Ternatin is a highly methylated cyclic heptapeptide isolated from mushroom Coriolus versicolor. Ternatin has an inhibitory effect on fat accumulation in 3T3-L1 adipocytes. [d-Leu7]ternatin, a ternatin derivative, also inhibited fat accumulation in 3T3-L1 cells, although the effectiveness of [d-Leu7]ternatin was lower than that of ternatin. In this study, we investigated the effects of ternatin and [d-Leu7]ternatin on obesity and type 2 diabetes in KK-Ay mice, an animal model for spontaneously developed type 2 diabetes. We continuously administered ternatin (8.5 or 17nmol/day) or [d-Leu7]ternatin (68nmol/day) to mice via a subcutaneous osmotic pump. Unexpectedly, neither ternatin nor [d-Leu7]ternatin affected body weight or adipose tissue weight in KK-Ay mice. In contrast, it was demonstrated that both ternatin and [d-Leu7]ternatin suppress the development of hyperglycemia. In liver, the SREBP-1c mRNA level tended to be lower or significantly decreased in mice treated with ternatin or [d-Leu7]ternatin, respectively. Moreover, we found that ternatin directly lowered the SREBP-1c mRNA level in Hepa1-6 hepatocyte cells. This study showed that ternatin and [d-Leu7]ternatin each had a preventive effect on hyperglycemia and a suppressive effect on fatty acid synthesis in KK-Ay mice.