Insulin resistance

Disease

Biology

Glucose homeostasis

Endocrinology

Insulin

Metabolism

Insulin receptor

Internal medicine

Fatty liver

Homeostasis

Medicine

Steatosis

Citric acid cycle

Glycolysis

Proceedings of the National Academy of Sciences

Inactivating mutations in the copper transporter Atp7b result in Wilson’s disease. The Atp7b −/− mouse develops hallmarks of Wilson’s disease. The activity of several nuclear receptors decreased in Atp7b −/− mice, and nuclear receptors are critical for maintaining metabolic homeostasis. Therefore, we anticipated that Atp7b −/− mice would exhibit altered progression of diet-induced obesity, fatty liver, and insulin resistance. Following 10 wk on a chow or Western-type diet (40% kcal fat), parameters of glucose and lipid homeostasis were measured. Hepatic metabolites were measured by liquid chromatography–mass spectrometry and correlated with transcriptomic data. Atp7b −/− mice fed a chow diet presented with blunted body-weight gain over time, had lower fat mass, and were more glucose tolerant than wild type (WT) littermate controls. On the Western diet, Atp7b −/− mice exhibited reduced body weight, adiposity, and hepatic steatosis compared with WT controls. Atp7b −/− mice fed either diet were more insulin sens...

Metabolic dysregulation in the <i>Atp7b</i> <sup>−/−</sup> Wilson’s disease mouse model

Metabolic dysregulation in the Atp7b −/− Wilson’s disease mouse model

Metabolic dysregulation in the Atp7b ^−/− Wilson’s disease mouse model