Hyperlipidemia induced in regucalcin transgenic rats: Involvement of adiponectin (pp. 105-120)
Authors: (Masayoshi Yamaguchi)
Abstract: Regucalcin is known as a regulatory protein in various intracellular signaling systems. Regucalcin transgenic (TG) rat was generated to determine the role of regucalcin in metabolic disorders. Regucalcin TG rat has been found to induce hyperlipidemia with increasing age (14 to 50 weeks); serum triglyceride, high-density lipoprotein (HDL)-cholesterol, free fatty acid, albumin, and calcium concentrations are markedly increased in the TG male and female rats with increasing age. The decrease in lipid and glycogen contents in the liver tissues was induced in regucalcin TG rats. The expression of leptin mRNA in the adipose and liver tissues was decreased in regucalcin TG rats of 50 weeks old. Adiponectin mRNA levels were not changed in the adipose tissues of regucalcin TG rats of 50 weeks old, while its expression was decreased in the liver tissues. Leptin and adiponectin are adipokines that are involved in lipid metabolism. These decreases may be partly involved in the hyperlipidemia induced in regucalcin TG rats. Moreover, overexpression of regucalcin has been shown to enhance glucose utilization and lipid production in the cloned rat hepatoma H4-II-E cells in vitro, and insulin resistance is seen in the cells. The expression of glucose transporter 2 mRNA was increased in the transfectants which overexpress regucalcin, while the expressions of insulin receptor and phosphatidylinositol 3-kinase mRNAs that are involved in insulin signaling. It is proposed that regucalcin is related to hyperlipidemia and that the
regucalcin TG rat model may be useful to determine the pathophysiological state and the development of therapeutic tool for hyperlipidemia.