This study investigated the characteristics of obesity induced by a high-fat diet (HD) over 13 weeks in Rhbdf2 gene knockout (KO) mice. Forty 7-week-old Rhbdf2 wild and KO mice were used and the mice were divided into 4 groups: Wild-ND (n=10, Rhbdf2 wild mice, normal diet (ND)), Wild-HD (n=10, Rhbdf2 wild mice, HD), KO-ND (n=10, Rhbdf2 KO mice, ND) and KO-HD (n=10, Rhbdf2 KO mice, HD). The relative epididymal fat weight in KO-HD was significantly increased compared with that in KO-ND (P<0.01). The relative liver and spleen weights in KO-HD were decreased compared with those in Wild-HD (p < 0.05) and KO-ND (p < 0.01). The mRNA expression of SOD1 in KO-ND was significantly reduced compared with that in Wild-ND (p < 0.05). In Wild-ND and HD, the mRNA expressions of TNF-α and IL-6 in epididymal fat were significantly increased compared with those in KO-ND and HD (p < 0.01). A significant increase of TNF- α and IL-6 mRNA expression was observed in KO-HD compared with KO-ND (p < 0.01). These results indicated that Rhbdf2 genes may regulate high fat diet-induced obesity damage by anti-inflammatory and anti-oxidative roles in fat tissue of mice.

N-ethyl-N-nitrosourea (ENU) is a potent mutagen in a mouse model by inducing point mutation in a random manner and, in particular, causing heritable base substitutions in spermatogonia. In this study, systematic development of phenotype-driven mutant mice with large scale was carried out by using ENU. Nine-week-old male mice of C57BL/6J received intraperitoneal injection at three times with 100 mg/kg of ENU at weekly intervals for three weeks. After injections with ENU, the changes of body weight, fatality, recovery of fertile period, and breeding record were measured in these mice. Body weight lost as a result of ENU treatments was reversed after the last ENU injection. Live fertile male mice recovered from infertility from 104 to 165 days after ENU treatments were mated with C57BL/6J female mice for generation of G1 offspring. An average birth rate was 5.9 mice from 1 pair of paternal and maternal mice. All of 231 G1 offspring mice were analyzed by modified-SHIRPA with standard procedure at nine weeks of age. Among G1 mice, 166 mice were identified as mutagenic phenotypes in 20 test items. The changes in mutagenic phenotypes after ENU treatments, for instance, pattern in the region with a different color, touch escape, changes in head morphology, pupil, and teeth, and negative geotaxis etc., were found in these mice. Taken together, these results indicate that ENU may be a trans-generational mutagen in C57BL/6J mice.

This study was performed to investigate the anti-obesity and anti-lipidemic ability of linalool (LL) in ApoE deficient mice fed a high-fat diet (HFD). Mice were divided into four experimental groups of eight each. Mice in the control group received a basic diet and oral repeated dose of the vehicle only for 12 weeks; mice in the HFD group received a HFD and oral repeated dose of the vehicle only for 12 weeks; and the HFD&LL25 and HFD&LL50 groups received a HFD and oral repeated dose of LL 25 and 50 mg/kg/day for 12 weeks, respectively. Mice in the HFD group showed a significant increase in body weight, spleen weight, and adipose tissue weight, compared with the control group. An increase in the serum levels of aspartate aminotransferase and alanine aminotransferase activities, total cholesterol (T-CHO), triglyceride (TG), and low density lipoprotein cholesterol was also observed in the HFD group. Histopathological examinations showed severe liver injuries, characterized by extensive fatty changes and hepatocyte degeneration/necrosis. On the contrary, oral administration with LL resulted in significantly improved HFD-induced obesity and hyperlipidemia, indicated by a decrease in adipose tissue weight, T-CHO, TG, and histopathological lesions. The results indicate that LL suppressed HFD-induced obesity, hyperlipidemia, hypercholesterolemia, and hepatic steatosis, suggesting that LL might be a promising adjuvant therapy for treatment of these metabolic disorders related to corpulence.