Disruption of klotho gene causes an abnormal energy homeostasis in mice

Biochem Biophys Res Commun. 2000 Nov 30;278(3):665-70. doi: 10.1006/bbrc.2000.3864.


klotho mice, which genetically lack klotho gene expression, are characterized with various systemic phenotypes resembling human aging, and also with growth retardation. Here we show that klotho mice have a barely detectable amount of the white adipose tissue but their brown adipose tissue (BAT) is comparably preserved. Glucose tolerance and insulin sensitivity in klotho mice are increased compared to those in wild-type mice as revealed by intraperitoneal glucose and insulin tolerance tests. Uncoupling protein-1 gene expression of BAT and body temperature in klotho mice are lower than those in wild-type mice, suggesting that klotho mice have less energy expenditure than wild-type mice. Histological examination suggests that klotho mice possess 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 homeostasis in klotho mice are very similar to those reported under food-restricted conditions. However, the amount of food intake is not different between klotho 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / anatomy & histology*
  • Adipose Tissue, Brown / anatomy & histology*
  • Adipose Tissue, Brown / pathology
  • Aging
  • Animals
  • Blood Glucose / metabolism
  • Body Weight
  • Energy Metabolism / genetics*
  • Glucuronidase
  • Homeostasis
  • Humans
  • Insulin / pharmacology
  • Insulin / physiology
  • Liver / enzymology
  • Liver / pathology
  • Liver Glycogen / metabolism
  • Male
  • Membrane Proteins / genetics*
  • Mice
  • Mice, Mutant Strains
  • Models, Animal
  • Organ Size
  • Pancreas / pathology
  • Phosphoenolpyruvate Carboxykinase (GTP) / genetics


  • Blood Glucose
  • Insulin
  • Liver Glycogen
  • Membrane Proteins
  • Glucuronidase
  • klotho protein
  • Phosphoenolpyruvate Carboxykinase (GTP)