Nonalcoholic Steatohepatitis (NASH) in OB/OB Mice Treated with Yo Jyo Hen Shi Ko (YHK)

Effects on Peroxisome Proliferator-Activated Receptors (PPARs) and Microsomal Triglyceride Transfer Protein (MTP)

Stefano, José Tadeu
Marques Souza de Oliveira, Claudia Pinto
Corrêa-Giannella, Maria Lúcia
de Lima, Vicência Mara Rodrigues
de Sá, Sandra Valéria
de Oliveira, Ellen Pierre
de Mello, Evandro Sobroza
Giannella-Neto, Daniel
Alves, Venâncio Avancini Ferreira
Carrilho, Flair José

University of Sao Paulo School of Medicine, Department of Gastroenterology (LIM-07), Sao Paulo, SP, Brazil (Stefano) (de Oliveira) (de Lima) (de Oliveira) (Carrilho)
University of Sao Paulo School of Medicine, Laboratory for Cellular and Molecular Endocrinology (LIM-25), Sao Paulo, SP, Brazil (Corrêa-Giannella) (de Sá) (Giannella-Neto)
University of Sao Paulo School of Medicine, Department of Pathology (LIM-14), Sao Paulo, SP, Brazil (de Mello) (Alves)

J. T. Stefano, University of Sao Paulo School of Medicine, Av. Dr. Enéas de Carvalho Aguiar no. 255, Instituto Central 9159, 05403–000 Sao Paulo, Brazil e-mail: [email protected]

Received: 14 December 2006 / Accepted: 13 February 2007 /Published online: 30 March 2007 © Springer Science+Business Media, LLC 2007

Digestive Diseases & Sciences 52(12):p 3448-3454, December 2007.

YHK has antioxidant properties, has a hypo-glycemic effect, and may reduce plasma lipid levels. In this study, we examined the hepatic expression of PPAR-α and -γ and MTP in ob/ob mice receiving or not receiving YHK. Ob/ob mice were assigned to receive oral YHK (20 mg/kg/day) fed solution (methionine/choline-deficient [MCD] diet + YHK group) or vehicle (MCD group) by gavage for 4 weeks. Liver fragments were collected for his-tologic examination and mRNA isolation. PPAR-α and -γ and MTP gene expression was examined by RT-qPCR. YHK treatment was associated with NASH prevention, weight loss, and reduction of visceral fat and of serum concentrations of aminotransferases in comparison to the MCD group. YHK promoted an increment in PPAR-α and MTP and a decrement in PPAR-γ mRNA contents. These findings suggest that modulation of PPAR-α and -γ and MTP RNA expression may be implicated in the protective effect of YHK in experimental NASH, limiting hepatocyte lipid accumulation.