title: Sitagliptin can inhibit the development of hepatic steatosis in high-fructose diet-fed ob/ob mice.
abstract: The beneficial effect of dipeptidyl peptidase-4 inhibition on diet-induced extra-pancreatic effects, especially on liver tissue remains poorly understood. Thus, we made the experimental designs as follows; five-week-old male ob/ob mice, which develop type 2 diabetic mellitus and nonalcoholic fatty liver disease by taking a high-carbohydrate diet (HCD), were divided into a group in which a HCD was given for 8 weeks as control, and another in which a HCD added with 0.0018% sitagliptin was given for 8 weeks. Hepatic steatosis was seen in all mice, but the mean grade of steatosis in the sitagliptin-administrated mice was significantly decreased. The acetyl-CoA concentrations were lower in sitagliptin-administrated mice, although the differences were not significant. However, the malonyl-CoA concentrations were significantly lower in sitagliptin-administrated mice. The expression of acetyl-CoA carboxylase 1 was inhibited in sitagliptin-administrated mice, irrespective of expressions of carbohydrate responsive element-binding protein (ChREBP) or sterol regulatory element-binding protein (SREBP)-1c. In conclusion, sitagliptin may affect the development of nonalcoholic fatty liver disease by inhibiting the production of malonyl-CoA and thus synthesis of fatty acids in the liver.
authors.affiliation: 2nd Department of Internal Medicine, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki, Osaka 569-8686, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Sujishi
authors.affiliation: 2nd Department of Internal Medicine, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki, Osaka 569-8686, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Fukunishi
authors.affiliation: Department of Pharmacology, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki, Osaka 569-8686, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Ii
authors.affiliation: 2nd Department of Internal Medicine, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki, Osaka 569-8686, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Nakamura
authors.affiliation: 2nd Department of Internal Medicine, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki, Osaka 569-8686, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Yokohama
authors.affiliation: 2nd Department of Internal Medicine, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki, Osaka 569-8686, Japan.
authors.forename: Hideko
authors.initials: H
authors.lastname: Ohama
authors.affiliation: 2nd Department of Internal Medicine, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki, Osaka 569-8686, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Tsuchimoto
authors.affiliation: 2nd Department of Internal Medicine, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki, Osaka 569-8686, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Asai
authors.affiliation: 2nd Department of Internal Medicine, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki, Osaka 569-8686, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Tsuda
authors.affiliation: 2nd Department of Internal Medicine, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki, Osaka 569-8686, Japan.
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Higuchi
keywords: ACC1; GLP-1; high-fructose; sitagliptin; steatosis