A high‐fructose diet in rats induces systemic iron deficiency and hepatic iron overload by an inflammation mechanism. Issue 1 (2nd December 2020)

• Record Type: Journal Article
• Authors: Wang, Chao; Wang, Xing; Song, Guangyao; Xing, Hanying; Yang, Linquan; Han, Kang; Chang, Yan‐Zhong
• Is Part Of: Journal of food biochemistry. Volume 45:Issue 1(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-12-02
• Subjects: high‐fructose diet -- inflammation -- iron metabolism -- NAFLD; Food -- Analysis -- Periodicals; Food -- Composition -- Periodicals; Biochemistry -- Periodicals; 664.024
• DOI: 10.1111/jfbc.13578
• Languages: English
• ISSNs: 0145-8884

Abstract

Abstract: Nonalcoholic fatty liver disease (NAFLD) correlates with the high intake of fructose‐rich soft drinks. Both inflammation and dysregulated iron metabolism are pathogenic factors in the development of NAFLD. The present investigation assessed the effects of a high‐fructose diet (HF diet) on inflammation and iron metabolism. In this study, rats were fed a control or HF diet for 4, 8, or 12 weeks, after which insulin resistance, transaminases levels, serum and liver lipid profiles, inflammatory factors, and iron metabolism‐related molecules were evaluated. The activities of the hepatic inflammation‐associated pathways, IKKβ/NF‐κB, and JAK2/STAT3, were detected by western blot. Result showed that the HF diet‐fed animals developed a time‐dependent serum lipid increase and hepatic lipid accumulation as well as insulin resistance. Serum iron (SI), serum ferritin (SF), and transferrin saturation (TS) decreased while total iron‐binding capacity (TIBC) and serum transferrin (s‐TF) increased at 8 and 12 weeks in the HF diet group. The HF diet led to increased transaminases levels at 8 and 12 weeks, and iron deposition was observed in the liver, accompanied by an upregulation of ferritin light chain (FTL), hepcidin (HEPC), transferrin (TF), transferrin receptor 1 (TfR1), iron regulatory protein 1 (IRP1), hemojuvelin (HJV), and divalent metal transporter 1 (DMT1). Moreover, ferroportin (FPN1) levels were downregulated, as expected from the increased HEPC. A progressive inflammation phenotype was apparent, with increased inflammatory factors, MDA, IL‐1β, IL‐6, and TNF‐α, in the serum and liver tissue. Concomitantly, the hepatic IKKβ/NF‐κB and JAK2/STAT3 pathways were activated. In summary, we verified that HF diet induces systemic iron deficiency and hepatic iron accumulation, likely due to the activation of inflammation via the NF‐κB and JAK2/STAT3 pathways. Practical applications: As increasing numbers of individuals consume HF diets, the health implications of this type of over nutrition become globally relevant. Using a high‐fructose diet rat model, our present study reveals inflammation as the link between a HF diet and dysregulated iron metabolism. Importantly, both inflammation and disrupted iron metabolism have been shown to be pathogenic factors in nonalcoholic fatty liver disease (NAFLD). The iron regulatory hormone, HEPC, is a link between the liver, inflammation, and iron metabolism. As fructose‐rich foods become increasingly abundant and people's fructose intake increases, the impact of high fructose on health requires increased attention. Little research has been conducted on the effects of fructose on iron metabolism. Our study provides useful insights into the prevention and treatment of iron metabolism disorders arising from metabolic syndrome. Abstract : The HF diet induces systematic iron deficiency and hepatic iron accumulation. Decreased FPN1 inhibits iron release, which may be a key reason in liver iron elevation caused by HF diet in rats. The increased HEPC down‐regulate ferroportin (FPN1) expression in liver levels were, as expected from the increased HEPC, the activation of inflammation via the NF‐κB and JAK2/STAT3 pathways in high‐fructose intake