title: Asperuloside stimulates metabolic function in rats across several organs under high-fat diet conditions, acting like the major ingredient of Eucommia leaves with anti-obesity activity.
abstract: Eucommia leaves (Eucommia ulmoides Oliver) 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 with Eucommia leaf 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.
authors.affiliation: Laboratory of Molecular Prophylaxis and Pharmacology, Department of Pharmaceutical Sciences , Suzuka University of Medical Science , 3500-3 Minamitamagaki-cho, Suzuka, Mie 513-8670 , Japan ; Department of Biochemistry and Proteomics , Mie University Graduate School of Medicine , 2-174 Edobashi, Tsu, Mie 514-8507 , Japan.
authors.forename: Takahiko
authors.initials: T
authors.lastname: Fujikawa
authors.affiliation: R&D Center , Kobayashi Pharmaceutical Co. Ltd , 1-30-3 Toyokawa, Ibaraki, Osaka 567-0057 , Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Hirata
authors.affiliation: R&D Center , Kobayashi Pharmaceutical Co. Ltd , 1-30-3 Toyokawa, Ibaraki, Osaka 567-0057 , Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Hosoo
authors.affiliation: R&D Center , Kobayashi Pharmaceutical Co. Ltd , 1-30-3 Toyokawa, Ibaraki, Osaka 567-0057 , Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Nakajima
authors.affiliation: R&D Center , Kobayashi Pharmaceutical Co. Ltd , 1-30-3 Toyokawa, Ibaraki, Osaka 567-0057 , Japan.
authors.forename: Atsunori
authors.initials: A
authors.lastname: Wada
authors.affiliation: Field Science Center of Kii Kuroshio Life Area , Mie University Graduate School of Bioresources , 1577 Kurimamachiya, Tsu, Mie 514-8507 , Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yurugi
authors.affiliation: Laboratory of Exercise Biochemistry, Graduate School of Comprehensive Human Sciences , Tsukuba University , Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki 305-8574 , Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Soya
authors.affiliation: Laboratory of Exercise Biochemistry, Graduate School of Comprehensive Human Sciences , Tsukuba University , Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki 305-8574 , Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Matsui
authors.affiliation: Department of Dentistry , Health Sciences University of Hokkaido , 1757 Kanazawa, Tobetsu-cho, Ishikari, Hokkaido 061-0293 , Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Yamaguchi
authors.affiliation: Department of Biochemistry and Proteomics , Mie University Graduate School of Medicine , 2-174 Edobashi, Tsu, Mie 514-8507 , Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Ogata
authors.affiliation: Department of Pharmaceutical Sciences , Health Sciences University of Hokkaido , 1757 Kanazawa, Tobetsu-cho, Ishikari, Hokkaido 061-0293 , Japan.
authors.forename: Sansei
authors.initials: S
authors.lastname: Nishibe
keywords: ASP, asperuloside; BAT, brown adipose tissue; Acadvl, acyl-CoA dehydrogenase, very long chain; Anti-obesity effects; Asperuloside; CHA, chlorogenic acid; Comp I, NADH dehydrogenase flavoprotein 1; Comp IV, cytochrome c oxidase, subunit 4a; Cpt1α, carnitine palmitoyltransferase 1α; Cs, citrate synthase; ELE, Eucommia leaf extract; Eucommia ulmoides Oliver; FA, fatty acid; Fas, fatty acid synthase; GEA, geniposidic acid; HFD, high-fat diet; Idh3α, isocitrate dehydrogenase 3α; Metabolic function; Ogdh, dihydrolipoamide succinyl transferase; Sol. M., soleus muscle; UCP, uncoupling protein; WAT, white adipose tissue