Mol. Cells 2018; 41(10):
Effects of Three Thiazolidinediones on Metabolic Regulation and Cold-Induced Thermogenesis
Jee Hyung Sohn1, Jong In Kim1, Yong Geun Jeon1, Jeu Park1, and Jae Bum Kim1,*
1National Creative Research Initiatives Center for Adipose Tissue Remodeling, Institute of Molecular Biology and Genetics, Department
of Biological Sciences, Seoul National University, Seoul 08826, Korea
Received July 9, 2018; Revised August 2, 2018; Accepted August 3, 2018.; Published online August 27, 2018.
© Korean Society for Molecular and Cellular Biology. All rights reserved.

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Insulin resistance is closely associated with metabolic diseases such as type 2 diabetes, dyslipidemia, hypertension and atherosclerosis. Thiazolidinediones (TZDs) have been developed to ameliorate insulin resistance by activation of peroxisome proliferator-activated receptor (PPAR) γ. Although TZDs are synthetic ligands for PPARγ, metabolic outcomes of each TZD are different. Moreover, there are lack of head-to-head comparative studies among TZDs in the aspect of metabolic outcomes. In this study, we analyzed the effects of three TZDs, including lobeglitazone (Lobe), rosiglitazone (Rosi), and pioglitazone (Pio) on metabolic and thermogenic regulation. In adipocytes, Lobe more potently stimulated adipogenesis and insulin-dependent glucose uptake than Rosi and Pio. In the presence of pro-inflammatory stimuli, Lobe efficiently suppressed expressions of pro-inflammatory genes in macrophages and adipocytes. In obese and diabetic db/db mice, Lobe effectively promoted insulin-stimulated glucose uptake and suppressed pro-inflammatory responses in epididymal white adipose tissue (EAT), leading to improve glucose intolerance. Compared to other two TZDs, Lobe enhanced beige adipocyte formation and thermogenic gene expression in inguinal white adipose tissue (IAT) of lean mice, which would be attributable to cold-induced thermogenesis. Collectively, these comparison data suggest that Lobe could relieve insulin resistance and enhance thermogenesis at low-concentration conditions where Rosi and Pio are less effective.
Keywords: adipogenesis, inflammation, insulin resistance,
PPARγ, thermogenesis

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30 September 2018 Volume 41,
Number 9, pp. 809~917

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