Early interplay of intra-hepatic iron and insulin resistance in children with non-alcoholic fatty liver disease

Manco, Melania; Alisi, Anna; Real, José Manuel Fernández; Equitani, Francesco; Vito, Rita De; Valenti, Luca; Nobili, Valério

doi:10.1016/j.jhep.2010.12.007

Cited by 38 publications

(33 citation statements)

References 38 publications

(42 reference statements)

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“…Our results are in line with previous reports in literature which demonstrated the high dose of iron supplementation with the NFD and HSFD groups decreased insulin sensitivity and increased iron accumulation in adipose tissue and major tissue involved in glucose and lipid metabolism [8,31,44] but this was not the case in the HMUFD group by which the diet was rich in olive oil (35.6%).…”

Section: Journal Of Clinical Nutrition and Dietetics Issn 2472-1921supporting

confidence: 93%

“…Furthermore, Fargion et al [35] demonstrated that iron status affects insulin sensitivity by modulating the transcription and membrane affinity of insulin receptor expression in the liver, and influencing insulin-dependent gene expression [36], but Manco et al [43] was not able to observe a significant difference between insulin sensitivity in patients with and without hepatic siderosis at short period of time, after assessing the intra-hepatic iron in non-alcoholic fatty liver disease (NAFLD) patients [44].…”

Section: Journal Of Clinical Nutrition and Dietetics Issn 2472-1921mentioning

confidence: 99%

“…It could have a significant effect on the response to the high iron diet or iron supplementation, and consequently affect insulin sensitivity. By reference to the articles that were discussed the role of fat type in insulin resistance, Storlien et al [44] found that not all types of fat lead to insulin resistance in rats [45]. In addition, Miret et al [45] demonstrated that olive oil-rich diet did not increase oxidative stress compared to fish oil-rich diet.…”

Section: Journal Of Clinical Nutrition and Dietetics Issn 2472-1921mentioning

confidence: 99%

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Iron Overload Effect on Serum Levels of Glucose, Insulin and HOMA-IR was Ifluenced by the Type of Fat in Female Sprague-Dawley Rats Fed High-Fat-Diets

Alkhatib¹,

Al-Domi²,

Shomaf³

et al. 2017

J Clin Nutr Diet

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Objective: This study was conducted to examine the effect of iron supplementation on serum levels of glucose, insulin and HOMA-IR, and to examine the histological iron deposition in tissue in female Sprague-Dawley rats fed high-fat-diets (HFDs). Methods:Rats were divided into three main groups: normal fat diet (NFD), high saturated fat diet (HSFD) and high monounsaturated fat diet (HMUSFD). After 6 weeks, rats were sub-divided into three sub-groups for intraperitonial injection of iron (control group, dose1 group (Do1); 15 mg/kg body weight (BW) and dose 2(Do2); (75 mg/kg BW). Serum glucose and insulin were measured. Also, the histological examination of iron deposition after Perl's Prussian staining was examined. Results:We indicated that a high dose of iron supplementation decreased total weight gain significantly by 3 folds in rats that were fed the NFD and 2.5 folds in rats that were fed the HMUFD as compared to control sub-groups (p˂0.05). Moreover, mean HOMA-IR levels increased significantly in rats received a high dose of iron as compared to controls in the NFD and the HSFD groups (p˂0.05) but not in HUSFD. However, liver iron accumulation was increased in HFDs groups compared to NFD. Conclusion:The findings showed that iron overload complications could be influenced by the degree of saturation of dietary fat. However, the high dose of iron supplementation decreased total weight gain and increased liver weight, accompanied by insulin resistance. It is noteworthy that the diet rich in olive oil could have a protective effect against insulin resistance and adipose tissue iron accumulation.

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Section: Journal Of Clinical Nutrition and Dietetics Issn 2472-1921supporting

confidence: 93%

Section: Journal Of Clinical Nutrition and Dietetics Issn 2472-1921mentioning

confidence: 99%

Section: Journal Of Clinical Nutrition and Dietetics Issn 2472-1921mentioning

confidence: 99%

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Iron Overload Effect on Serum Levels of Glucose, Insulin and HOMA-IR was Ifluenced by the Type of Fat in Female Sprague-Dawley Rats Fed High-Fat-Diets

Alkhatib¹,

Al-Domi²,

Shomaf³

et al. 2017

J Clin Nutr Diet

View full text Add to dashboard Cite

show abstract

“…Data obtained in recent studies by our group have been summarized in Supplementary Table 1. Furthermore, serum ferritin has been associated with the severity of insulin resistance [38][39][40]. (5) Ferroportin-1 (Fp-1) mutations and polymorphisms have been excluded as a common cause of iron overload in both DIOS and NAFLD/MetS [41,42].…”

Section: Key Pointsmentioning

confidence: 99%

Iron in fatty liver and in the metabolic syndrome: A promising therapeutic target

Dongiovanni

Fracanzani

Fargion

et al. 2011

Journal of Hepatology

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300

297

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The dysmetabolic iron overload syndrome (DIOS) is now a frequent finding in the general population, as is detected in about one third of patients with nonalcoholic fatty liver disease (NAFLD) and the metabolic syndrome. The pathogenesis is related to altered regulation of iron transport associated with steatosis, insulin resistance, and subclinical inflammation, often in the presence of predisposing genetic factors. Evidence is accumulating that excessive body iron plays a causal role in insulin resistance through still undefined mechanisms that probably involve a reduced ability to burn carbohydrates and altered function of adipose tissue. Furthermore, DIOS may facilitate the evolution to type 2 diabetes by altering beta-cell function, the progression of cardiovascular disease by contributing to the recruitment and activation of macrophages within arterial lesions, and the natural history of liver disease by inducing oxidative stress in hepatocytes, activation of hepatic stellate cells, and malignant transformation by promotion of cell growth and DNA damage. Based on these premises, the association among DIOS, metabolic syndrome, and NAFLD is being investigated as a new risk factor to predict the development of overt cardiovascular and hepatic diseases, and possibly hepatocellular carcinoma, but most importantly, represents also a treatable condition. Indeed, iron depletion, most frequently achieved by phlebotomy, has been shown to decrease metabolic alterations and liver enzymes in controlled studies in NAFLD. Additional studies are warranted to evaluate the potential of iron reductive therapy on hard clinical outcomes in patients with DIOS.

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“…The liver plays a central role in iron metabolism, and iron excess has been linked to the risk of development of certain chronic liver disorders such as hepatitis C virus infection [5], liver cirrhosis [6], and hepatocellular carcinoma [7]. However, its effect on NAFLD is controversial [8,9].…”

Section: Introductionmentioning

confidence: 99%

Circulating Iron Levels Interaction with Central Obesity on the Risk of Nonalcoholic Fatty Liver Disease: A Case–Control Study in Southeast China

et al. 2019

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Objectives: We aimed to evaluate the associations between body iron stores and the risk of nonalcoholic fatty liver disease (NAFLD) in a Chinese population and explore whether this effect may be modified by other factors. Methods: A 1: 1 frequency-matched case–control study was conducted, including 482 NAFLD cases and 490 gender- and age-matched controls. Serum levels of ferritin, hepcidin, and C-reactive protein were measured. Results: Multivariate logistic regression analysis showed that hepcidin was not associated with NAFLD risk; however, elevated serum ferritin was significantly associated with increased risk of NAFLD (adjusted OR 1.619, 95% CI 1.158–2.267), and hepcidin:ferritin ratio was significantly associated with decreased risk of NAFLD (OR_adjusted 0.702, 95% CI 0.501–0.984). When stratified by gender, a significant association was found between elevated serum ferritin and hepcidin:ferritin ratio and NAFLD only for women (OR_adjusted 2.131, 95% CI 1.151–3.944 and OR_adjusted 0.414, 95% CI 0.219–0.781, respectively). A significant multiplicative interaction between central obesity and elevated serum hepcidin was observed (p < 0.05). Conclusions: Elevated serum ferritin and hepcidin:ferritin ratio are associated with NAFLD in a Chinese population. Although serum hepcidin is not associated with NAFLD, it may augment the risk effect of central obesity on NAFLD.

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Early interplay of intra-hepatic iron and insulin resistance in children with non-alcoholic fatty liver disease

Cited by 38 publications

References 38 publications

Iron Overload Effect on Serum Levels of Glucose, Insulin and HOMA-IR was Ifluenced by the Type of Fat in Female Sprague-Dawley Rats Fed High-Fat-Diets

Iron Overload Effect on Serum Levels of Glucose, Insulin and HOMA-IR was Ifluenced by the Type of Fat in Female Sprague-Dawley Rats Fed High-Fat-Diets

Iron in fatty liver and in the metabolic syndrome: A promising therapeutic target

Circulating Iron Levels Interaction with Central Obesity on the Risk of Nonalcoholic Fatty Liver Disease: A Case–Control Study in Southeast China

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