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Open Access Research

Miglitol increases energy expenditure by upregulating uncoupling protein 1 of brown adipose tissue and reduces obesity in dietary-induced obese mice

Satoru Sugimoto1, Hisakazu Nakajima1*, Kazuki Kodo1, Jun Mori1, Kensuke Matsuo1, Kitaro Kosaka1, Wataru Aoi2, Kanji Yoshimoto3, Hiroshi Ikegaya3 and Hajime Hosoi1

Author Affiliations

1 Department of Pediatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465-Kajiicho, Hirokoji-Kawaramachi, Kamigyo-ku, Kyoto 602-8566, Japan

2 Laboratory of Health Science, Graduate School of Life and Environmental Sciences, Kyoto Prefectural University, Kyoto, Japan

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

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Nutrition & Metabolism 2014, 11:14  doi:10.1186/1743-7075-11-14

Published: 26 March 2014

Abstract

Background

Miglitol is an oral anti-diabetic drug that acts by inhibiting carbohydrate absorption in the small intestine. Recent studies have shown that miglitol reduces obesity in humans and rodents. However, its mechanisms have remained unclear. The purpose of this study was to determine whether miglitol generates heat by activating uncoupling protein 1 (UCP1), an enzyme involved in thermogenesis, in brown adipose tissue (BAT) in mice.

Methods

Four-week-old male C57BL/6 J mice were fed a high-fat diet alone (HF) or a high fat diet plus miglitol (HFM). Oxygen consumption (VO2) was used to estimate metabolic rate. A thermal imaging camera was used to quantify heat generation from interscapular brown adipose tissue. We analyzed the protein and gene expressions of UCP1 and the expressions of four proteins related to β3-adrenergic signaling in the pathway activating UCP1 (protein kinase A (PKA), hormone-sensitive lipase (HSL), p38 α mitogen-activated protein kinase (p38αMAPK) and peroxisome proliferator-activated receptor gamma coactivator 1α (PGC1α)).

Results

At 8 weeks, body weight, epididymal and subcutaneous white adipose tissue and the HOMA-R value of the HFM mice were significantly less than those of the HF mice. Food intake was not different between the HF and HFM mice. VO2 and BAT temperature were significantly higher in the HFM mice. Miglitol significantly enhanced the gene and protein expressions of UCP1 and the expressions of proteins related to β3-adrenergic signaling.

Conclusions

Miglitol’s anti-obesity effect was attributed to increased energy expenditure by upregulating UCP1 in BAT (i.e., by thermogenesis) and to enhancement of β3-adrenergic signaling in BAT.

Keywords:
Miglitol; Alpha-glucosidase inhibitor; Obesity; Oxygen consumption; Brown adipose tissue; Uncoupling protein 1; β3-adrenergic signaling