The Antidiabetic Drug Lobeglitazone Protects Mice from Lipogenesis-Induced Liver Injury via Mechanistic Target of Rapamycin Complex 1 Inhibition

Yu Seol Lee, Jeong Su Park, Da Hyun Lee, Dong Kyu Lee, Sung Won Kwon, Byung Wan Lee, Soo Han Bae

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

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.

Original languageEnglish
Article number539
JournalFrontiers in Endocrinology
Volume9
Issue numberSEP
DOIs
Publication statusPublished - 2018 Sep 21

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Lipogenesis
Hypoglycemic Agents
Liver
Wounds and Injuries
Endoplasmic Reticulum Stress
Thiazolidinediones
Type 2 Diabetes Mellitus
Insulin Resistance
lobeglitazone
Non-alcoholic Fatty Liver Disease
mechanistic target of rapamycin complex 1
Fatty Acids
Lipids
Glucose
Serum
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism

Cite this

Lee, Yu Seol ; Park, Jeong Su ; Lee, Da Hyun ; Lee, Dong Kyu ; Kwon, Sung Won ; Lee, Byung Wan ; Bae, Soo Han. / The Antidiabetic Drug Lobeglitazone Protects Mice from Lipogenesis-Induced Liver Injury via Mechanistic Target of Rapamycin Complex 1 Inhibition. In: Frontiers in Endocrinology. 2018 ; Vol. 9, No. SEP.
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The Antidiabetic Drug Lobeglitazone Protects Mice from Lipogenesis-Induced Liver Injury via Mechanistic Target of Rapamycin Complex 1 Inhibition. / Lee, Yu Seol; Park, Jeong Su; Lee, Da Hyun; Lee, Dong Kyu; Kwon, Sung Won; Lee, Byung Wan; Bae, Soo Han.

In: Frontiers in Endocrinology, Vol. 9, No. SEP, 539, 21.09.2018.

Research output: Contribution to journalArticle

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