Miglitol prevents diet-induced obesity by stimulating brown adipose tissue and energy expenditure independent of preventing the digestion of carbohydrates.

Abstract

Miglitol is an alpha-glucosidase inhibitor that improves post-prandial hyperglycemia, and it is the only drug in its class that enters the bloodstream. Anecdotally, miglitol lowers patient body weight more effectively than other alpha-glucosidase inhibitors, but the precise mechanism has not been addressed. Therefore, we analyzed the anti-obesity effects of miglitol in mice and in the HB2 brown adipocyte cell line. Miglitol prevented diet-induced obesity by stimulating energy expenditure without affecting food intake in mice. Long-term miglitol treatment dose-dependently prevented diet-induced obesity and induced mitochondrial gene expression in brown adipose tissue. The anti-obesity effect was independent of preventing carbohydrate digestion in the gastrointestinal tract. Miglitol effectively stimulated energy expenditure in mice fed a high-fat high-monocarbohydrate diet, and intraperitoneal injection of miglitol was sufficient to stimulate energy expenditure in mice. Acarbose, which is a non-absorbable alpha glucosidase inhibitor, also prevented diet-induced obesity, but through a different mechanism: it did not stimulate energy expenditure, but caused indigestion, leading to less energy absorption. Miglitol promoted adrenergic signaling in brown adipocytes in vitro. These data indicate that circulating miglitol stimulates brown adipose tissue and increases energy expenditure, thereby preventing diet-induced obesity. Further optimizing miglitol's effect on brown adipose tissue could lead to a novel anti-obesity drug.

• Authors: Tsutomu Sasaki, Mayumi Shimpuku, Tomoya Kitazumi, Haruna Hiraga, Yuko Nakagawa, Hiroshi Shibata, Yuko Okamatsu-Ogura, Osamu Kikuchi, Hye-jin Kim, Yuki Fujita, Jun Maruyama, Vina Yanti Susanti, Hiromi Yokota-Hashimoto, Masaki Kobayashi, Masayuki Saito, Tadahiro Kitamura
• Journal: Endocrine journal (Endocr J) Vol. 60 Issue 10 Pg. 1117-29 ( 2013) ISSN: 1348-4540 [Electronic] Japan
• PMID: 23995917 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Obesity Agents
• Dietary Carbohydrates
• Glycoside Hydrolase Inhibitors
• Hypoglycemic Agents
• Receptors, Adrenergic, beta
• miglitol
• 1-Deoxynojirimycin
• Acarbose

Topics

• 1-Deoxynojirimycin (analogs & derivatives, pharmacology)
• Acarbose (pharmacology)
• Adipocytes, Brown (metabolism)
• Adipose Tissue, Brown (drug effects, physiology)
• Animals
• Anti-Obesity Agents (therapeutic use)
• Cell Line
• Diet, High-Fat
• Dietary Carbohydrates (administration & dosage, metabolism)
• Digestion (drug effects)
• Eating (drug effects)
• Energy Metabolism (drug effects)
• Glycoside Hydrolase Inhibitors
• Hypoglycemic Agents (therapeutic use)
• Male
• Mice
• Mice, Inbred C57BL
• Obesity (prevention & control)
• Oxygen Consumption (drug effects)
• Receptors, Adrenergic, beta (physiology)
• Signal Transduction (drug effects)