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 ma...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 mito-chondrial 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 dys-regulation of lipid metabolism,and reviews current knowledge on the effects of copper overload on extrahepatic energy metabolism.展开更多
基金This work was supported by the National Institutes of Health-National Institute of Diabetes and Digestive and Kidney Diseases,USA,through grantnumber R01DK104770 to V.Medici.
文摘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 mito-chondrial 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 dys-regulation of lipid metabolism,and reviews current knowledge on the effects of copper overload on extrahepatic energy metabolism.
