The Dipeptidyl Peptidase-4 Inhibitor Teneligliptin Attenuates Hepatic Lipogenesis via AMPK Activation in Non-Alcoholic Fatty Liver Disease Model Mice
Non-alcoholic fatty liver disease (NAFLD), which is strongly associated with metabolic syndrome, is increasingly a major cause of hepatic disorder. Dipeptidyl peptidase (DPP)-4 inhibitors, anti-diabetic agents, are expected to be effective for the treatment of NAFLD. In the present study, we establi...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2015-12-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | http://www.mdpi.com/1422-0067/16/12/26156 |
| _version_ | 1811232347717107712 |
|---|---|
| author | Takayasu Ideta Yohei Shirakami Tsuneyuki Miyazaki Takahiro Kochi Hiroyasu Sakai Hisataka Moriwaki Masahito Shimizu |
| author_facet | Takayasu Ideta Yohei Shirakami Tsuneyuki Miyazaki Takahiro Kochi Hiroyasu Sakai Hisataka Moriwaki Masahito Shimizu |
| author_sort | Takayasu Ideta |
| collection | DOAJ |
| description | Non-alcoholic fatty liver disease (NAFLD), which is strongly associated with metabolic syndrome, is increasingly a major cause of hepatic disorder. Dipeptidyl peptidase (DPP)-4 inhibitors, anti-diabetic agents, are expected to be effective for the treatment of NAFLD. In the present study, we established a novel NAFLD model mouse using monosodium glutamate (MSG) and a high-fat diet (HFD) and investigated the effects of a DPP-4 inhibitor, teneligliptin, on the progression of NAFLD. Male MSG/HFD-treated mice were divided into two groups, one of which received teneligliptin in drinking water. Administration of MSG and HFD caused mice to develop severe fatty changes in the liver, but teneligliptin treatment improved hepatic steatosis and inflammation, as evaluated by the NAFLD activity score. Serum alanine aminotransferase and intrahepatic triglyceride levels were significantly decreased in teneligliptin-treated mice (p < 0.05). Hepatic mRNA levels of the genes involved in de novo lipogenesis were significantly downregulated by teneligliptin (p < 0.05). Moreover, teneligliptin increased hepatic expression levels of phosphorylated AMP-activated protein kinase (AMPK) protein. These findings suggest that teneligliptin attenuates lipogenesis in the liver by activating AMPK and downregulating the expression of genes involved in lipogenesis. DPP-4 inhibitors may be effective for the treatment of NAFLD and may be able to prevent its progression to non-alcoholic steatohepatitis. |
| first_indexed | 2024-04-12T11:01:40Z |
| format | Article |
| id | doaj.art-ca44bf235ee3400aaabd8615461b6528 |
| institution | Directory Open Access Journal |
| issn | 1422-0067 |
| language | English |
| last_indexed | 2024-04-12T11:01:40Z |
| publishDate | 2015-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-ca44bf235ee3400aaabd8615461b65282022-12-22T03:35:57ZengMDPI AGInternational Journal of Molecular Sciences1422-00672015-12-011612292072921810.3390/ijms161226156ijms161226156The Dipeptidyl Peptidase-4 Inhibitor Teneligliptin Attenuates Hepatic Lipogenesis via AMPK Activation in Non-Alcoholic Fatty Liver Disease Model MiceTakayasu Ideta0Yohei Shirakami1Tsuneyuki Miyazaki2Takahiro Kochi3Hiroyasu Sakai4Hisataka Moriwaki5Masahito Shimizu6Department of Gastroenterology, Internal Medicine, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, JapanDepartment of Gastroenterology, Internal Medicine, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, JapanDepartment of Gastroenterology, Internal Medicine, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, JapanDepartment of Gastroenterology, Internal Medicine, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, JapanDepartment of Gastroenterology, Internal Medicine, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, JapanDepartment of Gastroenterology, Internal Medicine, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, JapanDepartment of Gastroenterology, Internal Medicine, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, JapanNon-alcoholic fatty liver disease (NAFLD), which is strongly associated with metabolic syndrome, is increasingly a major cause of hepatic disorder. Dipeptidyl peptidase (DPP)-4 inhibitors, anti-diabetic agents, are expected to be effective for the treatment of NAFLD. In the present study, we established a novel NAFLD model mouse using monosodium glutamate (MSG) and a high-fat diet (HFD) and investigated the effects of a DPP-4 inhibitor, teneligliptin, on the progression of NAFLD. Male MSG/HFD-treated mice were divided into two groups, one of which received teneligliptin in drinking water. Administration of MSG and HFD caused mice to develop severe fatty changes in the liver, but teneligliptin treatment improved hepatic steatosis and inflammation, as evaluated by the NAFLD activity score. Serum alanine aminotransferase and intrahepatic triglyceride levels were significantly decreased in teneligliptin-treated mice (p < 0.05). Hepatic mRNA levels of the genes involved in de novo lipogenesis were significantly downregulated by teneligliptin (p < 0.05). Moreover, teneligliptin increased hepatic expression levels of phosphorylated AMP-activated protein kinase (AMPK) protein. These findings suggest that teneligliptin attenuates lipogenesis in the liver by activating AMPK and downregulating the expression of genes involved in lipogenesis. DPP-4 inhibitors may be effective for the treatment of NAFLD and may be able to prevent its progression to non-alcoholic steatohepatitis.http://www.mdpi.com/1422-0067/16/12/26156AMPKDPP-4 inhibitorlipogenesisnon-alcoholic fatty liver diseaseNAFLDSREBP1cteneligliptin |
| spellingShingle | Takayasu Ideta Yohei Shirakami Tsuneyuki Miyazaki Takahiro Kochi Hiroyasu Sakai Hisataka Moriwaki Masahito Shimizu The Dipeptidyl Peptidase-4 Inhibitor Teneligliptin Attenuates Hepatic Lipogenesis via AMPK Activation in Non-Alcoholic Fatty Liver Disease Model Mice International Journal of Molecular Sciences AMPK DPP-4 inhibitor lipogenesis non-alcoholic fatty liver disease NAFLD SREBP1c teneligliptin |
| title | The Dipeptidyl Peptidase-4 Inhibitor Teneligliptin Attenuates Hepatic Lipogenesis via AMPK Activation in Non-Alcoholic Fatty Liver Disease Model Mice |
| title_full | The Dipeptidyl Peptidase-4 Inhibitor Teneligliptin Attenuates Hepatic Lipogenesis via AMPK Activation in Non-Alcoholic Fatty Liver Disease Model Mice |
| title_fullStr | The Dipeptidyl Peptidase-4 Inhibitor Teneligliptin Attenuates Hepatic Lipogenesis via AMPK Activation in Non-Alcoholic Fatty Liver Disease Model Mice |
| title_full_unstemmed | The Dipeptidyl Peptidase-4 Inhibitor Teneligliptin Attenuates Hepatic Lipogenesis via AMPK Activation in Non-Alcoholic Fatty Liver Disease Model Mice |
| title_short | The Dipeptidyl Peptidase-4 Inhibitor Teneligliptin Attenuates Hepatic Lipogenesis via AMPK Activation in Non-Alcoholic Fatty Liver Disease Model Mice |
| title_sort | dipeptidyl peptidase 4 inhibitor teneligliptin attenuates hepatic lipogenesis via ampk activation in non alcoholic fatty liver disease model mice |
| topic | AMPK DPP-4 inhibitor lipogenesis non-alcoholic fatty liver disease NAFLD SREBP1c teneligliptin |
| url | http://www.mdpi.com/1422-0067/16/12/26156 |
| work_keys_str_mv | AT takayasuideta thedipeptidylpeptidase4inhibitorteneligliptinattenuateshepaticlipogenesisviaampkactivationinnonalcoholicfattyliverdiseasemodelmice AT yoheishirakami thedipeptidylpeptidase4inhibitorteneligliptinattenuateshepaticlipogenesisviaampkactivationinnonalcoholicfattyliverdiseasemodelmice AT tsuneyukimiyazaki thedipeptidylpeptidase4inhibitorteneligliptinattenuateshepaticlipogenesisviaampkactivationinnonalcoholicfattyliverdiseasemodelmice AT takahirokochi thedipeptidylpeptidase4inhibitorteneligliptinattenuateshepaticlipogenesisviaampkactivationinnonalcoholicfattyliverdiseasemodelmice AT hiroyasusakai thedipeptidylpeptidase4inhibitorteneligliptinattenuateshepaticlipogenesisviaampkactivationinnonalcoholicfattyliverdiseasemodelmice AT hisatakamoriwaki thedipeptidylpeptidase4inhibitorteneligliptinattenuateshepaticlipogenesisviaampkactivationinnonalcoholicfattyliverdiseasemodelmice AT masahitoshimizu thedipeptidylpeptidase4inhibitorteneligliptinattenuateshepaticlipogenesisviaampkactivationinnonalcoholicfattyliverdiseasemodelmice AT takayasuideta dipeptidylpeptidase4inhibitorteneligliptinattenuateshepaticlipogenesisviaampkactivationinnonalcoholicfattyliverdiseasemodelmice AT yoheishirakami dipeptidylpeptidase4inhibitorteneligliptinattenuateshepaticlipogenesisviaampkactivationinnonalcoholicfattyliverdiseasemodelmice AT tsuneyukimiyazaki dipeptidylpeptidase4inhibitorteneligliptinattenuateshepaticlipogenesisviaampkactivationinnonalcoholicfattyliverdiseasemodelmice AT takahirokochi dipeptidylpeptidase4inhibitorteneligliptinattenuateshepaticlipogenesisviaampkactivationinnonalcoholicfattyliverdiseasemodelmice AT hiroyasusakai dipeptidylpeptidase4inhibitorteneligliptinattenuateshepaticlipogenesisviaampkactivationinnonalcoholicfattyliverdiseasemodelmice AT hisatakamoriwaki dipeptidylpeptidase4inhibitorteneligliptinattenuateshepaticlipogenesisviaampkactivationinnonalcoholicfattyliverdiseasemodelmice AT masahitoshimizu dipeptidylpeptidase4inhibitorteneligliptinattenuateshepaticlipogenesisviaampkactivationinnonalcoholicfattyliverdiseasemodelmice |