Non-alcoholic fatty liver disease (NAFLD) is a metabolic disorder closely linked with type II diabetes (T2D). The progression of NAFLD is associated with the induction of lipogenesis through hyperactivation of the mechanistic target of rapamycin complex 1 (mTORC1) pathway. An increase in lipogenesis induces endoplasmic reticulum (ER) stress and accelerates oxidative liver injury in the pathogenesis of NAFLD. Lobeglitazone, one of thiazolidinediones (TZDs), is used as an antidiabetic drug to lower serum glucose level through an increase in insulin sensitivity. It is known to improve pathological symptoms in animals and humans with NAFLD. However, the underlying molecular mechanism of the protective effects of lobeglitazone against NAFLD has not been elucidated. Here, we show that under the physiological condition of acute lipogenesis, lobeglitazone inhibits hepatic lipid synthesis, the subsequent ER stress, and ?-oxidation of fatty acids by inhibiting the mTORC1 pathway. As a result, lobeglitazone protected mice from lipogenesis-induced oxidative liver injury. Taken together, lobeglitazone might be a suitable drug for the treatment of patients with diabetes and NAFLD.
Bibliographical noteFunding Information:
This work was supported by the National Research Foundation of Korea (NRF-2017R1A2B4007400 to SB; NRF-2017R1D1A1B03032808 to JP) and a Faculty Research Grant from the Yonsei University College of Medicine (6-2015-0099 to SB). The study was also supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health and Welfare, Republic of Korea (HI17C0913 and HI16C0257 to SB).
This work was supported by the National Research Foundation of Korea (NRF-2017R1A2B4007400 to SB; NRF-2017R1D1A1B03032808 to JP) and a Faculty Research Grant from the Yonsei University College of Medicine (6-2015-0099 to SB). The study was also supported by a grant from
© 2018 Lee, Park, Lee, Lee, Kwon, Lee and Bae.
All Science Journal Classification (ASJC) codes
- Endocrinology, Diabetes and Metabolism