title: The alpha-glucosidase inhibitor acarbose prevents obesity and simple steatosis in sequestosome 1/A170/p62 deficient mice.
abstract: OBJECTIVE
  Sequestosome 1 (SQSTM1)/A170/p62 plays an important role in membrane-receptor mediated signal transduction and autophagic protein degradation. Although the mechanism involved is not clear, sqstm1 gene knockout (KO) mice develop mature-onset obesity and insulin resistance, leading to type II diabetes. KO mice show accumulation of fat in white adipose tissue and the liver when fed a standard diet. Acarbose is an alpha-glucosidase inhibitor that improves insulin sensitivity and decreases postprandial hyperglycemia, and it is used to treat type 2 diabetes. We examined whether or not dietary acarbose prevented obesity and simple steatosis in KO mice.
  
  
  METHODS
  Wild-type (WT) and KO mice were fed a standard diet with or without acarbose (0.8% w/w) from 15-25 weeks of age. The body weight and the fat content of adipose tissue and the liver were measured, and changes of lipid metabolism in these tissues were assessed from gene expression.
  
  
  RESULTS
  Acarbose treatment suppressed weight gain and the development of hepatic steatosis in KO mice. Acarbose treatment up-regulated hepatic expression of the pparalpha, ucp-2, and abca1 genes, as well as srebp1c, pparalpha, and ppargamma in adipose tissue. In WT mice, however, acarbose treatment had little influence on weight gain and gene expression.
  
  
  CONCLUSIONS
  The results of this study suggest that long-term administration of acarbose is effective for prevention of obesity and simple steatosis in SQSTM1-KO mice.
authors.affiliation: Department of Gastroenterology, University of Tsukuba, Tsukuba, Japan.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Okada
authors.forename: Toru
authors.initials: T
authors.lastname: Yanagawa
authors.forename: Eiji
authors.initials: E
authors.lastname: Warabi
authors.forename: Keiko
authors.initials: K
authors.lastname: Yamastu
authors.forename: Junya
authors.initials: J
authors.lastname: Uwayama
authors.forename: Koichi
authors.initials: K
authors.lastname: Takeda
authors.forename: Hirotoshi
authors.initials: H
authors.lastname: Utsunomiya
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yoshida
authors.forename: Junichi
authors.initials: J
authors.lastname: Shoda
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Ishii