Distinct Phenotype of Non-Alcoholic Fatty Liver Disease in Patients With Low Levels of Free Copper and of Ceruloplasmin

Abstract

BACKGROUND: Copper deficiency has been linked to alterations in lipid metabolism and hepatic steatosis. Oxidative stress plays a role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). One of the enzymes that neutralize oxidative stress is Cu/Zn superoxide dismutase, which depends on the availability of adequate amounts of copper. OBJECTIVE: Correlate the levels of ceruloplasmin and of non-ceruloplasmin-bound copper (NCBC) with clinical, biochemical and histological parameters of non-alcoholic fatty liver disease (NAFLD) patients. METHODS: Data from 95 consecutively admitted NAFLD patients who underwent liver biopsy composed the groups based on ceruloplasmin levels lower than 25 mg/dL and on negative NCBC. The risk factors for NAFLD in each group were compared. RESULTS: Body mass index was lower in patients with ceruloplasmin <25 mg/dL (29.1±3.47 vs 32.8±6.24 kg/m2; P=0.005) as were the levels of LDL, HDL and total cholesterol, when compared with their counterparts with ceruloplasmin >25 mg/dL (101±38 vs 116±35 mg/dL, P=0.05; 43±9 vs 51±16 mg/dL, P=0.01; 174±43 vs 197±39 mg/dL, P=0.01, respectively). Mean serum ferritin levels were higher in the ceruloplasmin <25 mg/dL group (343±327 vs 197±190 ng/mL; P=0.02). Otherwise, patients with negative NCBC had higher HOMA-IR (8.2±14.7 vs 4.6±3.7; P=0.03). Age, gender, hypertension and diabetes showed no statistical difference. CONCLUSION: Patients with NAFLD had different clinical and biochemical markers according to the levels of NCBC and ceruloplasmin.

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

“…There is evidence showing the association between low serum Cu and the accumulation of fat in the liver of animals [11][12][13]. A similar relationship has also been reported in humans [14]. The results of a study on 95 biopsy-proven NAFLD patients showed lower BMI, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and total cholesterol (TC) and higher levels of ferritin in those with low Cu status [14].…”

“…Serum CuD (<70 µg/dl) was found in 7.4% of healthy subjects and 2.4% of NAFLD patients while all subjects showed normal serum Cer concentration (>20 g/L). A number of animal studies have reported low serum levels of Cu in association with fat accumulation in the liver [11,14]. Moreover, there is evidence revealing CuD in humans [14].…”

“…A number of animal studies have reported low serum levels of Cu in association with fat accumulation in the liver [11,14]. Moreover, there is evidence revealing CuD in humans [14]. For example, Lan et al [24] in 1816 cases of NAFLD and 1111 sex-and age-matched controls in China reported a statistically significant trend of the relationship of higher Cu concentration with reduced risk of NAFLD in men (Ptrend < 0.001).…”

Research Progress on Oxidative Stress and Its Nutritional Regulation Strategies in Pigs

“…Copper: One of the enzymes that neutralize oxidative stress is Cu/Zn SOD, which has some ability to scavenge ROS; hence, adequate levels of copper in the body are important to mitigate oxidative stress [ 131 , 132 ]. The addition of cholesterol to the animal diet can lead to copper deficiency and, thus, promote oxidative damage [ 133 ].…”

Pathophysiological Mechanisms in Non-Alcoholic Fatty Liver Disease: From Drivers to Targets

“…Liver-related innate immune responses to excess fat can directly result in hepatocyte apoptosis [ 15 ]. However, inflammation may precede steatosis, as inflammatory events may lead to lipid accumulation [ 16 , 17 ]. Therefore, inflammatory processes may play key roles in the pathogenesis of fatty liver diseases.…”