Disruption of klotho gene causes an abnormal energy homeostasis in mice

klotho mice, which genetically lack klotho gene expression, are characteriz ed with various systemic phenotypes resembling human aging, and also with g rowth retardation. Here we show that klotho mice have a barely detectable a mount of the white adipose tissue but their brown adipose tissue (BAT) is c omparably preserved. Glucose tolerance and insulin sensitivity in klotho mi ce are increased compared to those in wild-type mice as revealed by intrape ritoneal glucose and insulin tolerance tests. Uncoupling protein-1 gene exp ression of BAT and body temperature in klotho mice are lower than those in wild-type mice, suggesting that klotho mice have less energy expenditure th an wild-type mice. Histological examination suggests that klotho mice posse ss less energy storage than wild-type mice with respect to glycogen in the liver and lipid in BAT. All these changes of parameters for energy homeosta sis in klotho mice are very similar to those reported under food-restricted conditions. However, the amount of food intake is not different between kl otho and wild-type mice when normalized for body weight. The present study elucidates the importance of klotho gene expression for the maintenance of normal energy homeostasis. (C) 2000 Academic Press.