Serum copper, ceruloplasmin, and their relations to metabolic factors in nonalcoholic fatty liver disease: a cross-sectional study

Abstract

Objective Nonalcoholic fatty liver disease (NAFLD) characterized by excessive intrahepatic fat accumulation is increasing worldwide. This study aimed to investigate serum copper (Cu) and ceruloplasmin (Cer) levels and their relations to metabolic factors in NAFLD. Methods This cross-sectional study was conducted on 141 subjects with NAFLD diagnosed using abdominal ultrasonography. Personal information, anthropometric measures, glucose and lipid profile, and serum levels of liver enzymes were assessed. Fasting serum levels of Cu and Cer were determined using colorimetry and nephelometry assay, respectively. Odds ratios (ORs) were used to examine the associations of serum Cu and Cer levels with NAFLD risk. Results The results on 85 patients with NAFLD and 56 apparently healthy participants showed that all NAFLD cases and 53.6% of the healthy subjects were overweight or obese. More than half of the patients (58.8%) showed mild NAFLD. Age, weight, BMI, lipid profile, uric acid, and ferritin were significantly higher in NAFLD patients than the healthy cases. No significant differences were found in the concentrations of Cu and Cer between the groups. Only 7.4% of the healthy subjects and 2.4% of the patients were Cu deficient (<70 µg/dl). No association was found between the risk of NAFLD and serum Cu [OR: 0.994; 95% confidence interval (CI): 0.981-1.006] and Cer levels (OR: 0.414; 95% CI: 0.001-123.604) after adjusting for the confounders. Conclusion Our findings revealed no association between Cu deficiency and NAFLD risk. Further human studies with larger sample sizes are required to investigate how Cu and Cer status may affect NAFLD.

Association between micronutrients intake and metabolic-associated fatty liver disease: a cross-sectional study based on the National Health and Nutrition Examination Survey

“…First, higher intake of copper may exert an antioxidant effect to reduce oxidative stress and decrease lipid synthesis, which retards the progression of MAFLD. ( 34 ) Second, fatty liver diseases are linked to insulin resistance, ( 35 ) higher intake of copper may decrease hepatic steatosis and insulin resistance. ( 31 )…”

“…First, higher intake of copper may exert an antioxidant effect to reduce oxidative stress and decrease lipid synthesis, which retards the progression of MAFLD. (34) Second, fatty liver diseases are linked to insulin resistance, (35) higher intake of copper may decrease hepatic steatosis and insulin resistance. (31) In this study, we also found the association between high intake of copper and the low odds of MAFLD in patients in male or female, with or without diabetes, with or without hypertension, indicating that the association between dietary copper intake and MAFLD was not affected by gender, diabetes, and hypertension.…”

Urine Proteome in Distinguishing Hepatic Steatosis in Patients with Metabolic-Associated Fatty Liver Disease

“…In one study, both Cu and serum ceruloplasmin were negatively associated with siderosis, ferritin, and HOMA-IR, but not liver steatosis [ 58 ]. Another cross-sectional study also found no association between the risk of NAFLD and serum Cu and ceruloplasmin levels [ 12 ]. On the contrary, some researchers found that Cu is elevated in visceral adipose tissue and liver, with little steatosis in obese patients, likely due to the concurrent increase in ceruloplasmin [ 62 , 63 ].…”

“…Hepatic steatosis is the first step of MAFLD diagnosis, and it is a risk predictor that independently predicts insulin resistance, cardiovascular risk, and mortality [ 8 , 9 , 10 , 11 , 12 , 13 ]. Liver biopsy is still the gold standard to assess liver steatosis, ballooning, and lobular inflammation, as in previous NAFLD and NASH diagnoses.…”

Comparison of copper concentration between non-alcoholic fatty liver disease patients and normal individuals: A meta-analysis

“…A typical example is Wilson's disease, an overloaded hepatic copper accumulation and insufficient ceruloplasmin with liver steatosis, inflammation, and cuprotosis ( 9 ). However, recent studies demonstrate the association between copper deficiency and the accumulation of fat in the liver, and NAFLD patients with hepatic copper deficiency show more severe liver steatosis, inflammation, and clinical symptoms ( 10 , 11 ). Besides, rats fed with a restricted copper diet will spontaneously develop liver steatosis ( 12 ).…”