Lipid and energy metabolism in Wilson disease()

Copper accumulation and deficiency are reciprocally connected to lipid metabolism. In Wilson disease (WD), which is caused by a genetic loss of function of the copper-transporting P-type ATPase beta, copper accumulates mainly in the liver and lipid metabolism is dysregulated. The underlying mechanisms linking copper and lipid metabolism in WD are not clear. Copper may impair metabolic machinery by direct binding to protein and lipid structures or by generating reactive oxygen species with consequent damage to cellular organelles vital to energy metabolism. In the liver, copper overload results in mitochondrial impairment, down-regulation of lipid metabolism, and the development of steatosis with an etiology not fully elucidated. Little is known regarding the effect of copper overload on extrahepatic energy homeostasis. This review aims to discuss alterations in hepatic energy metabolism associated with WD, highlights potential mechanisms involved in the development of hepatic and systemic dysregulation of lipid metabolism, and reviews current knowledge on the effects of copper overload on extrahepatic energy metabolism.