Iron overload potentiates diet‐induced hypercholesterolemia and reduces liver ppar‐α expression in hamsters

Bonomo, L; Silva, Maísa; Oliveira, Riva de Paula; Silva, Marcelo Eustáquio; Pedrosa, Maria Lúcia

doi:10.1002/jbt.21410

Cited by 12 publications

(12 citation statements)

References 22 publications

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“…Iron dextran decreased pparα expression, suggesting that it would decrease FA oxidation, thus increasing serum triacylglycerol concentration. Bonomo et al [ 7 ] showed similar effect of iron on the expression of PPAR alpha in hypercholesterolemic hamsters; however this study did not evaluate triacylglycerol metabolism. Oxidative stress and inflammation modulate PPAR receptors in diabetes [ 13 ], suggesting that increased oxidative stress promoted by iron dextran may have resulted in the decreased pparα expression, this was also correlated in this study.…”

Section: Discussionmentioning

confidence: 88%

“…The generation of free radicals might be involved in dyslipidemia and consequently in the pathogenesis of hepatic steatosis [ 3 ] and cardiovascular disease [ 4 ]. Previous data suggests a link between lipids and iron metabolism and that this relationship is influenced by oxidative stress [ 5 – 7 ]. However, despite a considerable amount of data indicating an increase of both O 2 − and iron content in tissue leads to increased OH − formation, the mechanism of involvement and the role of iron in early stage dyslipidemia remain to be elucidated.…”

Section: Introductionmentioning

confidence: 99%

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Iron Dextran Increases Hepatic Oxidative Stress and Alters Expression of Genes Related to Lipid Metabolism Contributing to Hyperlipidaemia in Murine Model

Silva

Guerra

Sampaio

et al. 2015

BioMed Research International

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The objective of this study was to investigate the effects of iron dextran on lipid metabolism and to determine the involvement of oxidative stress. Fischer rats were divided into two groups: the standard group (S), which was fed the AIN-93M diet, and the standard plus iron group (SI), which was fed the same diet but also received iron dextran injections. Serum cholesterol and triacylglycerol levels were higher in the SI group than in the S group. Iron dextran was associated with decreased mRNA levels of pparα, and its downstream gene cpt1a, which is involved in lipid oxidation. Iron dextran also increased mRNA levels of apoB-100, MTP, and L-FABP indicating alterations in lipid secretion. Carbonyl protein and TBARS were consistently higher in the liver of the iron-treated rats. Moreover, a significant positive correlation was found between oxidative stress products, lfabp expression, and iron stores. In addition, a negative correlation was found between pparα expression, TBARS, carbonyl protein, and iron stores. In conclusion, our results suggest that the increase observed in the transport of lipids in the bloodstream and the decreased fatty acid oxidation in rats, which was promoted by iron dextran, might be attributed to increased oxidative stress.

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Section: Discussionmentioning

confidence: 88%

Section: Introductionmentioning

confidence: 99%

Iron Dextran Increases Hepatic Oxidative Stress and Alters Expression of Genes Related to Lipid Metabolism Contributing to Hyperlipidaemia in Murine Model

Silva

Guerra

Sampaio

et al. 2015

BioMed Research International

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“…Silva et al () showed that intraperitoneal injection of iron dextran could decrease fatty acid oxidation in the liver of rats by the inhibition of PPARα and its target genes. In addition, Bonomo et al () showed a similar effect of intraperitoneal injection of iron dextran on the expression of PPARα in hypercholesterolemic hamsters. It is well known that heme iron is better absorbed than non‐heme iron (Seligman et al .…”

Section: Discussionmentioning

confidence: 85%

Effects of dietary heme iron and exercise training on abdominal fat accumulation and lipid metabolism in high‐fat diet‐fed mice

Katsumura

Takagi

Oya

et al. 2016

Animal Science Journal

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Animal by-products can be recycled and used as sources of essential nutrients. Water-soluble heme iron (WSHI), a functional food additive for supplementing iron, is produced by processing animal blood. In this study, we investigated the effects of dietary supplementation of 3% WSHI and exercise training for 4 weeks on the accumulation of abdominal fat and lipid metabolism in mice fed high-fat diet. Exercise-trained mice had significantly less perirenal adipose tissue, whereas WSHI-fed mice tended to have less epididymal adipose tissue. In addition, total weight of abdominal adipose tissues was significantly decreased in the Exercise + WSHI group. Dietary WSHI significantly increased the messenger RNA (mRNA) levels of lipoprotein lipase and hormone-sensitive lipase. WSHI-fed mice also tended to show increased mRNA levels of adipose triglyceride lipase in their epididymal adipose tissue. Dietary WSHI also significantly decreased the mRNA levels of fatty acid oxidation-related enzymes in the liver, but did not influence levels in the Gastrocnemius muscle. Exercise training did not influence the mRNA levels of lipid metabolism-related enzymes in the epididymal adipose tissue, liver or the Gastrocnemius muscle. These findings suggest that the accumulation of abdominal fat can be efficiently decreased by the combination of dietary WSHI and exercise training in mice fed high-fat diet.

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“…Some animal and epidemiological studies have suggested that high iron levels may have a harmful impact on glucose and lipid metabolism [154][155][156]. It is noteworthy that iron overload attenuates the hepatic expression of Ppar-α, which is an important transcriptional factor that promotes lipid and lipoprotein metabolism [113]. Bonomo et al [113] reported evidence that iron is involved in the pathogenesis of non-alcoholic steatohepatitis (NASH).…”

Section: Ironmentioning

confidence: 99%

“…It is noteworthy that iron overload attenuates the hepatic expression of Ppar-α, which is an important transcriptional factor that promotes lipid and lipoprotein metabolism [113]. Bonomo et al [113] reported evidence that iron is involved in the pathogenesis of non-alcoholic steatohepatitis (NASH). Their data showed that intraperitoneal injection of iron dextran, when associated with a high-fat diet (HFD), caused increased serum cholesterol levels due to a reduction in Ppar-α mRNA expression in the liver tissue of hamsters.…”

Section: Ironmentioning

confidence: 99%

Trace Elements, PPARs, and Metabolic Syndrome

Shi

Zou

Shen

et al. 2020

IJMS

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Metabolic syndrome (MetS) is a constellation of metabolic derangements, including central obesity, insulin resistance, hypertension, glucose intolerance, and dyslipidemia. The pathogenesis of MetS has been intensively studied, and now many factors are recognized to contribute to the development of MetS. Among these, trace elements influence the structure of proteins, enzymes, and complex carbohydrates, and thus an imbalance in trace elements is an independent risk factor for MetS. The molecular link between trace elements and metabolic homeostasis has been established, and peroxisome proliferator-activated receptors (PPARs) have appeared as key regulators bridging these two elements. This is because on one hand, PPARs are actively involved in various metabolic processes, such as abdominal adiposity and insulin sensitivity, and on the other hand, PPARs sensitively respond to changes in trace elements. For example, an iron overload attenuates hepatic mRNA expression of Ppar-α; zinc supplementation is considered to recover the DNA-binding activity of PPAR-α, which is impaired in steatotic mouse liver; selenium administration downregulates mRNA expression of Ppar-γ, thereby improving lipid metabolism and oxidative status in the liver of high-fat diet (HFD)-fed mice. More importantly, PPARs' expression and activity are under the control of the circadian clock and show a robust 24 h rhythmicity, which might be the reasons for the side effects and the clinical limitations of trace elements targeting PPARs. Taken together, understanding the casual relationships among trace elements, PPARs' actions, and the pathogenesis of MetS is of great importance. Further studies are required to explore the chronopharmacological effects of trace elements on the diurnal oscillation of PPARs and the consequent development of MetS.

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Iron overload potentiates diet‐induced hypercholesterolemia and reduces liver ppar‐α expression in hamsters

Cited by 12 publications

References 22 publications

Iron Dextran Increases Hepatic Oxidative Stress and Alters Expression of Genes Related to Lipid Metabolism Contributing to Hyperlipidaemia in Murine Model

Iron Dextran Increases Hepatic Oxidative Stress and Alters Expression of Genes Related to Lipid Metabolism Contributing to Hyperlipidaemia in Murine Model

Effects of dietary heme iron and exercise training on abdominal fat accumulation and lipid metabolism in high‐fat diet‐fed mice

Trace Elements, PPARs, and Metabolic Syndrome

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