Marginal copper and high fat diet produce alterations in electrocardiograms and cardiac ultrastructure in male rats

Mao, Shumin; Medeiros, Denis M.; Hamlin, Robert L.

doi:10.1016/s0899-9007(99)00156-2

Cited by 8 publications

(6 citation statements)

References 24 publications

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“…This decrease in body weight indicates that Cu is essential for normal growth and development as an integral part of many enzymes, which are dependent on Cu for their normal activity. However, another study revealed that a diet marginally deficient in Cu did not affect the feed intake and weight gain of rats (16).…”

Section: Discussionmentioning

confidence: 95%

Alterations of Liver Histomorphology in Relation to Copper Supplementation in Inorganic and Organic Form in Growing Rats

Tomaszewska

Dobrowolski

Kwiecień

et al. 2014

Bulletin of the Veterinary Institute in Pulawy

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The aim of this study was to define the effects of diet containing the same mineral content of mineral salt or amino acid chelate, and diet containing various levels of Cu amino acid chelate on liver histomorphometry in growing rats. Male Wistar rats were used in the 12th week experiment. The control group (n = 12) was fed standard diet, which provided Cu in an inorganic form at the level required for rats. The experimental animals were divided into four groups (each n = 12) depending on different levels (100%, 75%, 50%, 25% covered daily demand) of Cu supplementation in chelated form. Cu content was determined in the liver tissue and blood plasma. Immunohistochemical staining with caspase-3 antibody was performed. Microscopic assessment of the liver structure indicated that Cu supplementation did not change the liver architecture. However, histomorphometric analysis revealed a significant increase in the number of nuclei, total cell number, and multinucleated hepatocytes in rats supplemented with the organic form of Cu at the level of 25% compared with the control group. There was a considerable increase in the number of apoptotic cells and ballooning degeneration of hepatocytes, especially in groups supplemented with organic form of Cu covering the daily demand in 100% and 75%, in comparison to control group. Moreover, there was no Cu deposition in the liver and changes in Cu content in blood. Cu provided in the diet in organic form covering an amount of its minimum daily demand in 25% appears to be the least harmful with regard to the liver. It indicates that there is a need to establish the level of diet supplementation with Cu amino acid chelates.

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Section: Discussionmentioning

confidence: 95%

Alterations of Liver Histomorphology in Relation to Copper Supplementation in Inorganic and Organic Form in Growing Rats

Tomaszewska

Dobrowolski

Kwiecień

et al. 2014

Bulletin of the Veterinary Institute in Pulawy

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“…Intriguingly, liver copper content was reduced by dietary fat content, consistent with the notion that obesity itself may lead to decreased copper levels (21). Marginal copper diets using higher levels of copper (2.5 ppm) displayed similar effects on hepatic copper when dietary fat was increased (54)(56). Therefore, the combination of high‐fat and marginally copper‐deficient diet may place organs at much greater risk of copper deficiency than either diet alone.…”

Section: Discussionmentioning

confidence: 99%

“…Under severe copper deficiency, in which rodent diets offer only ∼0.5 ppm, activity of copper‐dependent enzymes is dramatically attenuated, resulting in premature death within 6 to 8 weeks (24)(53). To circumvent such limitations in a chronic study such as the 12‐week feeding used in this work, marginal levels of dietary copper were introduced to achieve marginal copper deficiency (54)(55)(56). However, a consensus on the definition of “marginal copper deficiency” has not been well established.…”

Section: Discussionmentioning

confidence: 99%

“…However, a consensus on the definition of “marginal copper deficiency” has not been well established. Marginal levels of dietary copper have been defined as 50% to 60% of the recommended intake (54)(56). Animals subsisting on 30% of recommended copper levels, as used in this study, do not succumb to cardiac aneurysms or severe cardiomyopathy (24)(53).…”

Section: Discussionmentioning

confidence: 99%

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Dietary Interaction of High Fat and Marginal Copper Deficiency on Cardiac Contractile Function

Relling

Esberg

Johnson

et al. 2007

Obesity

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Objective: High‐fat and marginally copper‐deficient diets impair heart function, leading to cardiac hypertrophy, increased lipid droplet volume, and compromised contractile function, resembling lipotoxic cardiac dysfunction. However, the combined effect of the two on cardiac function is unknown. This study was designed to examine the interaction between high‐fat and marginally copper‐deficient diets on cardiomyocyte contractile function. Research Methods and Procedures: Weanling male rats were fed diets incorporating a low‐ or high‐fat diet (10% or 45% of kcal from fat, respectively) with adequate (6 mg/kg) or marginally deficient (1.5 mg/kg) copper content for 12 weeks. Contractile function was determined with an IonOptix system including peak shortening (PS), time‐to‐PS, time‐to‐90% relengthening, maximal velocity of shortening/relengthening, and intracellular Ca2+ ([Ca2+]I) rise and decay. Results: Neither dietary treatment affected blood pressure or glucose levels, although the high‐fat diet elicited obesity and glucose intolerance. Both diets depressed PS, maximal velocity of shortening/relengthening, and intracellular Ca2+ ([Ca2+]I) rise and prolonged time‐to‐90% relengthening and Ca2+ decay without an additive effect between the two. Ca2+ sensitivity, apoptosis, lipid peroxidation, nitrosative damage, tissue ceramide, and triglyceride levels were unaffected by either diet or in combination. Phospholamban (PLB) but not sarco(endo)plasmic reticulum Ca2+‐ATPase was increased by both diets. Endothelial NO synthase was depressed with concurrent treatments. The electron transport chain was unaffected, although mitochondrial aconitase activity was inhibited by the high‐fat diet. Discussion: These data suggest that high‐fat and marginally copper deficient diets impaired cardiomyocyte contractile function and [Ca2+]i homeostasis, possibly through a similar mechanism, without obvious lipotoxicity, nitrosative damage, and apoptosis.

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“…Previous studies have shown that rats fed a copper-deficient diet demonstrate decreased copper-dependent enzyme activity (15), impaired mitochondrial respiration (16), abnormal membrane pathology (3), and increased mitochondrial biogenesis (17).…”

Section: Discussionmentioning

confidence: 99%

Differential expression of genes involved with apoptosis, cell cycle, connective tissue proteins, fuel substrate utilization, inflammation and mitochondrial biogenesis in copper-deficient rat hearts: implication of a role for Nfκb1

Klaahsen

Ricklefs

Medeiros

2007

The Journal of Nutritional Biochemistry

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We hypothesized that the increase in mitochondrial proliferation in hearts from copper-deficient rats is due to an increase in expression of the transcriptional factor Ppargc1a, which regulates transcriptional activity for many of the genes that encode for mitochondrial proteins. In addition to several transcriptional factors implicated in mitochondrial biogenesis, we also looked at a number of genes involved in cell cycle regulation and fuel substrate utilization. Long-Evans rats were placed on either a copperadequate (n=4) or copper-deficient (n=4) diet 3 days post-weaning and remained on the diet for five weeks; their copper deficiency status was confirmed using previously established assays. Custom oligo arrays spotted with genes pertinent to mitochondrial biogenesis were hybridized with cRNA probes synthesized from the collected heart tissue. Chemiluminescent array images from both groups were analyzed for gene spot intensities and differential gene expression. Our results did not demonstrate any significant increase in Ppargc1a or its implicated targets, as we had predicted. However, consistent with previous data, an up-regulation of genes that encode for collagen type 3, fibronectin and elastin were found. Interestingly, there was also a significant increase in the expression of the transcriptional factor Nfκb1 in the copper-deficient treatment animals compared to the control group. The results of this study merit the further investigation of the role of ROS with regard to Nfkb1 in the copper deficient rat heart.

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Marginal copper and high fat diet produce alterations in electrocardiograms and cardiac ultrastructure in male rats

Cited by 8 publications

References 24 publications

Alterations of Liver Histomorphology in Relation to Copper Supplementation in Inorganic and Organic Form in Growing Rats

Alterations of Liver Histomorphology in Relation to Copper Supplementation in Inorganic and Organic Form in Growing Rats

Dietary Interaction of High Fat and Marginal Copper Deficiency on Cardiac Contractile Function

Differential expression of genes involved with apoptosis, cell cycle, connective tissue proteins, fuel substrate utilization, inflammation and mitochondrial biogenesis in copper-deficient rat hearts: implication of a role for Nfκb1

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