Abstract
Essential trace elements play crucial roles in the maintenance of health, since they are involved in many metabolic pathways. A deficiency or an excess of some trace elements, including zinc, selenium, iron, and copper, frequently causes these metabolic disorders such as impaired glucose tolerance and dyslipidemia. The liver largely regulates most of the metabolism of trace elements, and accordingly, an impairment of liver functions can result in numerous metabolic disorders. The administration or depletion of these trace elements can improve such metabolic disorders and liver dysfunction. Recent advances in molecular biological techniques have helped to elucidate the putative mechanisms by which liver disorders evoke metabolic abnormalities that are due to deficiencies or excesses of these trace elements. A genome-wide association study revealed that a genetic polymorphism affected the metabolism of a specific trace element. Gut dysbiosis was also responsible for impairment of the metabolism of a trace element. This review focuses on the current trends of four trace elements in chronic liver diseases, including chronic hepatitis, liver cirrhosis, nonalcoholic fatty liver disease, and autoimmune liver diseases. The novel mechanisms by which the trace elements participated in the pathogenesis of the chronic liver diseases are also mentioned.
Highlights
The liver plays indispensable roles in the maintenance of essential trace elements homeostasis [1,2].Most of the trace elements are absorbed from the duodenum and/or jejunum and flow out in the portal circulation by binding to the plasma proteins
We demonstrated that serum Se levels were reduced in proportion to the severity of hepatic fibrosis in patients with an hepatitis C virus (HCV)-related chronic liver diseases (CLDs) [34]
A genome-wide association (GWA) study identified a single nucleotide polymorphism (SNP) in rs738409 in the patatin-like phospholipase domain containing 3 (PNPLA3) gene, which is recognized as an adiponutrin gene, and the SNP was strongly associated with the grade of hepatic fat content [148]
Summary
The liver plays indispensable roles in the maintenance of essential trace elements homeostasis [1,2]. Most of the trace elements are absorbed from the duodenum and/or jejunum and flow out in the portal circulation by binding to the plasma proteins. These trace elements are distributed to the tissues or organs that require them. Impairments of the liver function result in disturbances of the metabolism of trace elements, leading to the initiation of oxidative stress and the subsequent inflammatory and/or fibrotic changes in the liver. The impairment of the homeostasis of trace elements leads to various inflammatory changes and/or metabolic abnormalities such as those observed in inflammatory bowel disease [4], diabetes mellitus [5], dyslipidemia [6], and sarcopenia [7] as well as chronic liver injuries.
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