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PLoS One. 2018 Jul 6;13(7):e0200336. doi: 10.1371/journal.pone.0200336. eCollection 2018.

Effects of lobeglitazone on insulin resistance and hepatic steatosis in high-fat diet-fed mice.

Author information

1
Department of Nuclear Medicine, College of Medicine, Gyeongsang National University Hospital, Gyeongsang National University, Jinju, Gyeongnam, Republic of Korea.
2
Department of Anatomy and Convergence Medical Science, Bio Anti-aging Medical Research Center, Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju, Gyeongnam, Republic of Korea.
3
EZmass Co., Ltd., Jinju, Gyeongnam, Republic of Korea.
4
Department of Thoracic and Cardiovascular Surgery, College of Medicine, Gyeongsang National University Hospital, Gyeongsang National University, Jinju, Gyeongnam, Republic of Korea.
5
Department of Food Science and Technology, Division of Applied Life Sciences (BK21 plus), Institute of Agriculture and Life Science, Gyeongsang National University, Jinju, Gyeongnam, Republic of Korea.
6
Division of Endocrinology and Metabolism, Department of Internal Medicine, Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju, Gyeongnam, Republic of Korea.

Abstract

Lobeglitazone (Lobe) is a novel thiazolidinedione antidiabetic drug that reduces insulin resistance by activating peroxisome proliferator-activated receptor-gamma (PPARγ). However, the exact mechanisms of antidiabetic effects of Lobe have not been established in an animal model. The aim of this study was to evaluate the hypoglycemic effects of Lobe and investigate possible factors involved in Lobe-enhanced hepatic steatosis in high-fat diet (HFD)-fed mice. Mice were fed an HFD for 15 weeks. Lobe was administrated orally during the last 9 weeks. Lobe treatment significantly reduced insulin resistance and increased expression of hepatic glucose transporter 4 (GLUT4) and PPARs in HFD-fed mice. However, increased body weight and hepatic steatosis were not reduced by Lobe in these mice. Metabolomics fingerprinting showed that several lipogenesis-related hepatic and serum metabolites in HFD-fed mice had positive or negative correlations with Lobe administration. In particular, increased leptin levels during HFD were further increased by Lobe. HFD-induced signaling transducer and activator of transcription 3 (STAT3) phosphorylation in the hypothalamus was increased by Lobe. In addition, immunohistochemical analysis showed more proopiomelanocortin (POMC)-positive neurons in the hypothalamus of HFD-fed mice (with or without Lobe) compared with normal diet-fed mice. Despite improving leptin signaling in the hypothalamus and enhancing insulin sensitivity in HFD-fed mice, Lobe increased body weight and steatosis. Further research is necessary regarding other factors affecting Lobe-enhanced hepatic steatosis and hyperphagia.

PMID:
29979770
PMCID:
PMC6034891
DOI:
10.1371/journal.pone.0200336
[Indexed for MEDLINE]
Free PMC Article

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