Hepatic gene expression profiles in persimmon peel extract administrated KK-Ay mice

We have shown in a previous study that the intake of persimmon peel (PP) extract altered hepatic gene expression of insulin signaling and enhanced tyrosine phosphorylation of insulin receptors in nonobese type 2 diabetic Goto–Kakizaki rats. We also showed the alteration of gene expression in fatty acid synthesis and metabolism. To evaluate the effect of PP extract on obese diabetic KK-Ay mice, we fed them a diet mixed with 0.1% of the extract for 8 weeks. The plasma total ketone bodies level of the treated mice were significantly lower than that of the untreated mice. The hepatic gene expression profiles of treated mice indicated upregulation of fatty acid biosynthesis-associated gene expression. Hepatic nonesterified palmitic acid content was higher in treated mice than in untreated mice. These results suggest that the intake of PP extract enhances hepatic fatty acid biosynthesis of KK-Ay mice, reducing their plasma total ketone bodies level. Five-week-old male KK-Ay/TaJcl mice were purchased from CREA Japan, Inc. (Tokyo, Japan). They were individually housed in plastic cages and maintained at 22 ± 1°C under a 12-h light/dark cycle (lights on from 08:00 to 20:00 daily). They were fed a commercial diet (AIN-93G, Oriental Yeast, Co., Ltd., Tokyo, Japan) for a week and then divided into two groups with similar average body weight: a control diet (CD) group (n = 7) fed a commercial diet and a PP extract diet (PD) group (n = 6) fed a commercial diet containing 1 g/kg of PP extract. The mice were allowed free access to food and drinking water. In both groups, the feeding period was 8 weeks, and body weights and food intakes were measured every day during the feeding period. After 8 weeks, each mouse was fasted for 3 h and then anesthetized with pentobarbital. Blood was collected from the carotid artery and treated with heparin. The blood was centrifuged at 800×g, and supernatants were collected and stored at−20°C until use. Livers were excised and treated with RNAlater for subsequent RNA analysis. The remaining liver tissues were frozen in liquid nitrogen and stored at −80°C until use. The protocol for the animal experiments was approved by the Animal Use Committee of the Faculty of Agriculture, University of Tokyo.