Copper Deficiency Increases In Vivo Hepatic Synthesis of Fatty Acids, Triacylglycerols, and Phospholipids in Rats

Abstract

This study examined the influence of dietary copper status on the in vivo hepatic fatty acid synthesis and the incorporation of nascent fatty acids into various hepatic lipid classes. Fifty weanling male Sprague-Dawley rats were assigned to two dietary treatments, copper deficient (5.4 nmol/g of diet) and copper adequate (102 nmol/g of diet). After 7 weeks of treatment, rats were injected with 0.111 MBq of [1-14C] acetate (1.85 GBq/mM)/100 g body wt through the femoral vein. Five rats from each treatment were sacrificed at 3, 6, 9, 12, and 24 min after injection. Radioactivities of nascent fatty acid samples were used to determine relative rates of fatty acid synthesis and their assembly into triacylglycerols and phospholipids. Linear increases were observed up to 12 min after injection for total hepatic fatty acid synthesis and their assembly into triacylglycerols and phospholipids for both treatments. In addition, 46% and 30% of total fatty acid synthesized were assembled into triacylglycerols and phospholipids, respectively, for both groups. Furthermore, hepatic fatty acid synthesis and assembly into triacylglycerols and phospholipids were enhanced more than 2-fold by copper deficiency when the data were expressed as per liver per 100 g body weight.

Lipid fluidity of triacylglycerol-rich lipoproteins isolated from copper-deficient rats

“…Studies on hepatic apolipoprotein synthesis indicate that apolipoprotein B 100 synthesis is increased in Cu-deficient rats (Nassir et al 1993). Thus, the hyperlipaemia observed appears to be sustained by an increase in hepatic lipoprotein synthesis (Al-Othman et al 1993). However, the possible contribution of defective uptake of plasma lipoproteins may also be involved in hyperlipaemia (Lei, 1990).…”

Low Hepatic Tissue Copper in Pediatric Nonalcoholic Fatty Liver Disease

“…Additionally, copper has been demonstrated to mediate lipid metabolism via increased size of circulating VLDL and expression of fatty-acid synthase in animal models 9, 10 Human studies in adults also report a correlation between low serum and hepatic tissue copper levels and NAFLD 11, 12 . Although this has been reported in adults, hepatic tissue copper content in children with NAFLD has yet to be characterized.…”

The Role of Copper as a Modifier of Lipid Metabolism

“…Although numerous studies clearly link copper deficiency to altered lipid metabolism in animal models (12,22,24,(89)(90)(91)(92) and human volunteers (29), only recently has low dietary copper been implicated in liver dyslipidemia pathology, including non-alcoholic fatty-liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). In a recent groundbreaking study, hepatic copper content in biopsy specimens was inversely correlated with the severity of fatty liver disease, and copper deficiency in a rodent model was found sufficient to induce NAFLD and metabolic syndrome (12).…”