Asperuloside stimulates metabolic function in rats across several organs under high-fat diet conditions, acting like the major ingredient ofEucommialeaves with anti-obesity activity

Takahiko Fujikawa1,2, Tetsuya Hirata3, Shingo Hosoo3, Kenji Nakajima3, Atsunori Wada3, Yutaka Yurugi4, Hideaki Soya5, Takashi Matsui5, Akihiko Yamaguchi6, Masato Ogata1, Sansei Nishibe7
1Department of Biochemistry and Proteomics, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan
2Laboratory of Molecular Prophylaxis and Pharmacology, Department of Pharmaceutical Sciences, Suzuka University of Medical Science, 3500-3 Minamitamagaki-cho, Suzuka, Mie 513-8670, Japan
3R&D Center, Kobayashi Pharmaceutical Co., Ltd., 1-30-3, Toyokawa, Ibaraki, Osaka 567-0057, Japan
4Field Science Center of Kii Kuroshio Life Area, Mie University Graduate School of Bioresources, 1577 Kurimamachiya, Tsu, Mie 514-8507, Japan
5Laboratory of Exercise Biochemistry, Graduate School of Comprehensive Human Sciences, Tsukuba University, Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki 305-8574, Japan
6Department of Dentistry, Health Sciences University of Hokkaido, 1757 Kanazawa, Tobetsu-cho, Ishikari, Hokkaido 061-0293, Japan
7Department of Pharmaceutical Sciences, Health Sciences University of Hokkaido, 1757 Kanazawa, Tobetsu-cho, Ishikari, Hokkaido 061-0293, Japan

Tóm tắt

AbstractEucommialeaves (Eucommia ulmoidesOliver) contain chlorogenic acid (a caffeic acid derivative) and geniposidic acid and asperuloside (ASP), iridoid glucosides used in beverages. We used a metabolic syndrome rat model, produced by feeding a 35 % high-fat diet (HFD), to examine potential anti-obesity and anti-metabolic syndrome effects and mechanisms of chronic administration of ASP. These effects were compared withEucommialeaf extract (ELE), the positive control, which exhibits anti-obesity effects. A total of six rats were studied for 3 months in five groups. ASP suppressed body weight, visceral fat weight, food intake and circulating levels of glucose, insulin and lipids, and increased the plasma adiponectin level in rats on a HFD. These effects are similar to those of ELE, except for the influence on the plasma glucose level. RT–PCR studies showed that ASP (like ELE with known anti-obesity effects) diminished isocitrate dehydrogenase 3α, NADH dehydrogenase flavoprotein 1 (Comp I) mRNA and fatty acid synthase levels (white adipose tissue), increased carnitine palmitoyltransferase 1α and acyl-CoA dehydrogenase, very-long-chain mRNA levels (liver), and increased Glut4, citrate synthase, isocitrate dehydrogenase 3α, succinyl CoA synthase, peroxisomal 3-ketoacyl-CoA thiolase, dihydrolipoamide succinyl transferase and succinate dehydrogenase mRNA levels (skeletal muscle) under HFD conditions. Interestingly, ASP administration resulted in significantly increased mRNA levels of uncoupling protein 1 (UCP1) in the brown adipose tissue of HFD-fed rats; ELE did not affect the expression of UCP1. The increased expression of UCP1 may be negated by many ingredients other than ASP in the ELE. These findings suggest that chronic administration of ASP stimulates anti-obesity and anti-metabolic syndrome activity in HFD-fed rats across several organs, similar to ELE administration; thus, ASP may be an important ingredient of ELE.

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