title: Enzamin ameliorates adipose tissue inflammation with impaired adipocytokine expression and insulin resistance in db/db mice.
abstract: The effects of Enzamin on obesity-related metabolic disorders in obese db/db mice were examined to explore a novel agent for the prevention of insulin resistance. Db/db mice were treated with water containing Enzamin (0·1 and 1·0 %) for 8 weeks from 6 weeks of age. Enzamin treatment at 1·0 %, but not at 0·1 %, significantly decreased the fasting plasma glucose, serum total cholesterol and TAG levels in db/db mice, without affecting body weight gain and body fat composition. Furthermore, insulin sensitivity and glucose tolerance were improved by the treatment of db/db mice with 1·0 % Enzamin. Immunohistochemical studies and gene expression analysis showed that 1·0 % Enzamin treatment suppressed macrophage accumulation and inflammation in the adipose tissue. In addition, 1·0 % Enzamin treatment increased serum adiponectin in db/db mice. Treatment with 1·0 % Enzamin also significantly suppressed the expression of NADPH oxidase subunits, suggesting an antioxidative effect for Enzamin in the adipose tissue. Furthermore, in vitro experiments demonstrated that the lipopolysaccharide-induced inflammatory reaction was significantly suppressed by Enzamin treatment in macrophages. Enzamin treatment increased the expression of GLUT4 mRNA in muscle, but not GLUT2 mRNA in the liver of db/db mice. Enzamin also increased the mRNA expression of carnitine palmitoyltransferase 1a (CPT1a, muscle isoform) in db/db mice, whereas Enzamin treatment did not affect the mRNA expression of CPT1b (liver isoform) in db/db mice. In conclusion, our data indicate that Enzamin can improve insulin resistance by ameliorating impaired adipocytokine expression, presumably through its anti-inflammatory action, and that Enzamin possesses a potential for preventing the metabolic syndrome.
authors.affiliation: Department of Physiology and Regenerative Medicine , Kinki University Faculty of Medicine , Osakasayama , Japan.
authors.forename: Yukinori
authors.initials: Y
authors.lastname: Tamura
authors.affiliation: Department of Physiology and Regenerative Medicine , Kinki University Faculty of Medicine , Osakasayama , Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Yano
authors.affiliation: Department of Physiology and Regenerative Medicine , Kinki University Faculty of Medicine , Osakasayama , Japan.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Kawao
authors.affiliation: Life Science Research Institute, Kinki University , Osakasayama , Japan.
authors.forename: Katsumi
authors.initials: K
authors.lastname: Okumoto
authors.affiliation: Department of Food Science and Nutrition , Kinki University Faculty of Agriculture , Nara , Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Ueshima
authors.affiliation: Department of Physiology and Regenerative Medicine , Kinki University Faculty of Medicine , Osakasayama , Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kaji
authors.affiliation: Kinki University Faculty of Medicine , Osakasayama , Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Matsuo
keywords: ATCC, American Type Culture Collection; Adipocytokines; CPT, carnitine palmitoyltransferase; CPT1a, carnitine palmitoyltransferase 1 (liver); CPT1b, carnitine palmitoyltransferase 1 (muscle); CT, computed tomography; Enzamin; Insulin resistance; LPS, lipopolysaccharide; MCP-1, monocyte chemoattractant protein 1; Macrophages; Nox2, NADPH oxidase 2; PAI-1, plasminogen activator inhibitor 1; t-PA, tissue-type plasminogen activator