ESPE Abstracts (2014) 82 P-D-2-3-386

ESPE2014 Poster Category 2 Fat Metabolism & Obesity (2) (23 abstracts)

Miglitol Upregulates Uncoupling Protein 1 (ucp1) by Enhancing β3-Adrenergic Signaling in Mature Brown Adipocytes of Rat

Satoru Sugimoto , Hisakazu Nakajima , Taichiro Nishikawa Nishikawa , Kazuki Kodo , Ikuyo Itoh , Kitaro Kosaka & Hajime Hosoi

Department of Pediatrics, Kyoto Prefectural University of Medicine Graduate School of Medical Science, Kyoto, Japan

Introduction: We previously reported that miglitol, an alpha-glucosidase inhibitor (α-GI), increases energy expenditure by enhancing β3-adrenergic signaling of brown adipose tissue (BAT) and reduces obesity in dietary-induced obese mice (S Sugimoto et al, at the 9th joint meeting of Pediatric Endocrinology, 2013) (Nutrition & Metabolism). However, this report did not describe the mechanism by which miglitol enhances β3-adrenergic signaling. Miglitol, unlike other α-GIs, enters the circulation. We hypothesized that miglitol acts in the blood where it directly enhances β3-adrenergic signaling.

Objective: The purpose of this study was to determine whether miglitol has a direct effect on β3-adrenergic signaling in mature brown adipocytes.

Methods: We used a rat brown adipocyte culture kit (Takara, Japan). After the cells finished maturing, we added medium containing miglitol with or without β3-adrenergic agonist CL316,243. After 24 h, the cells were harvested. The gene expressions of uncoupling of protein 1 (UCP1) and peroxisome proliferator-activated receptor gamma coactivator 1α (PGC1α) were analyzed by quantitative real-time PCR.

Results: Miglitol at concentrations of 5–50 μM had no effect on the gene expression of PGC1α and UCP1 in the absence of CL316,243, but in the presence of CL316,243, it significantly increased the expression of both genes.

Conclusion: Miglitol increased the sensitivity of β3-adrenergic receptor in mature brown adipocytes. This suggests that, in our experiment, miglitol entered the circulation where it directly enhanced β3-adrenergic signaling of BAT in mice.

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