title: A long-lasting dipeptidyl peptidase-4 inhibitor, teneligliptin, as a preventive drug for the development of hepatic steatosis in high-fructose diet-fed ob/ob mice.
abstract: Non-alcoholic fatty liver disease (NAFLD) occurs in patients with components of metabolic syndrome such as type 2 diabetes mellitus (T2DM). At present, the central pathophysiological problem in patients afflicted with NAFLD is insulin resistance. In this study, we aimed to determine the effects of a dipeptidyl peptidase-4 (DPP-4) inhibitor, teneligliptin, on the development of NAFLD in ob/ob mice. Five-week-old male ob/ob mice were divided into 4 experimental groups as follows: a group in which they were fed a high carbohydrate diet (HCD) for 8 weeks (n=8) as controls (control group 1), a group in which they were fed HCD supplemented with 0.018% teneligliptin for 8 weeks (n=8) (teneligliptin group 1), a group in which they were fed HCD for 12 weeks (n=8) as controls (control group 2), and another group in which they were fed only HCD for 4 weeks, and the HCD was then supplemented with 0.018% teneligliptin for 8 weeks (n=8) (teligliptin group 2). Hepatic steatosis was observed in all mice in the control group fed the HCD, but only mild hepatic steatosis was observed in teneligliptin group 1. Mice in teneligliptin group 1 fed the diet containing teneligliptin had lower hepatic triglyceride (TG) and free fatty acid (FFA) levels. Mice in teneligliptin group 1 exhibited improvement of insulin resistance; however, those in teneligliptin group 2 did not show any improvement of insulin resistance. Our results thus suggest that teneligliptin may be used as a preventative, but not as a treatment drug for the development of NAFLD.
authors.affiliation: Second Department of Internal Medicine, Osaka Medical College, Takatsuki, Osaka 569-8686, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Nakamura
authors.affiliation: Second Department of Internal Medicine, Osaka Medical College, Takatsuki, Osaka 569-8686, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Fukunishi
authors.affiliation: Second Department of Internal Medicine, Osaka Medical College, Takatsuki, Osaka 569-8686, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Yokohama
authors.affiliation: Second Department of Internal Medicine, Osaka Medical College, Takatsuki, Osaka 569-8686, Japan.
authors.forename: Hideko
authors.initials: H
authors.lastname: Ohama
authors.affiliation: Second Department of Internal Medicine, Osaka Medical College, Takatsuki, Osaka 569-8686, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Tsuchimoto
authors.affiliation: Second Department of Internal Medicine, Osaka Medical College, Takatsuki, Osaka 569-8686, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Asai
authors.affiliation: Second Department of Internal Medicine, Osaka Medical College, Takatsuki, Osaka 569-8686, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Tsuda
authors.affiliation: Second Department of Internal Medicine, Osaka Medical College, Takatsuki, Osaka 569-8686, Japan.
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Higuchi
mesh_terms: D000818:Animals; D004040:Dietary Carbohydrates / Q000009:adverse effects* / Q000494:pharmacology; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000494:pharmacology*; D005632:Fructose / Q000009:adverse effects* / Q000494:pharmacology; D008297:Male; D051379:Mice; D008820:Mice, Obese; D065626:Non-alcoholic Fatty Liver Disease / Q000139:chemically induced / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control; D011720:Pyrazoles / Q000494:pharmacology*; D053778:Thiazolidines / Q000494:pharmacology*
chemical_list: C579035:3-(4-(4-(3-methyl-1-phenyl-1H-pyrazol-5-yl)piperazin-1-yl)pyrrolidin-2-ylcarbonyl)thiazolidine; D004040:Dietary Carbohydrates; D054873:Dipeptidyl-Peptidase IV Inhibitors; D011720:Pyrazoles; D053778:Thiazolidines; D005632:Fructose; D018819:Dipeptidyl Peptidase 4; C545245:Dpp4 protein, mouse