Higher Hepcidin Levels in Adolescents with Obesity Are Associated with Metabolic Syndrome Dyslipidemia and Visceral Fat

Abstract

Tightly regulated iron metabolism prevents oxidative stress. Hepcidin is a hormone that regulates iron flow in plasma; its production is induced by an iron overload and by inflammation. It inhibits iron entry into the circulation by blocking dietary absorption in the duodenum, the release of recycled iron from macrophages and the exit of stored iron from hepatocytes. Varied signals responding to iron stores, erythropoietic activity and host defense converge to regulate hepcidin production and thereby affect iron homeostasis. Although it is known that hepcidin increases when interleukin 6 (IL-6) increases, the relationship between hepcidin, dyslipidemia, insulin resistance (IR) and visceral adiposity index (VAI) in adolescents with obesity is unclear. In this cross-sectional study of 29 obese adolescents and 30 control subjects, we explored the difference of hepcidin, iron metabolism markers and IL-6 between obese and non-obese adolescents, and identified associations with inflammation, atherogenic dyslipidemia and IR. As compared to lean controls, obese participants showed 67% higher hepcidin: 14,070.8 ± 7213.5 vs. 8419.1 ± 4826.1 pg/mLc; 70% higher ferritin: 94.4 ± 82.4 vs. 55.1 ± 39.6 pg/mLa and 120% higher IL-6: 2.0 (1.1–4.9) vs. 0.9 (0.5–1.3) pg/mLd. Transferrin, soluble transferrin receptor and total body iron (as measured by sTFR/ferritin, log10 sTFR/ferritin ratio and sTFR/log ferritin ratios) were not different between the two cohorts. In the whole cohort, hepcidin correlated with VAI (r = 0.29a), sd-LDL (r = 0.31b), HOMA-IR (r = 0.29a) and IL-6 (r = 0.35c). In obese adolescents hepcidin correlated with TG (r = 0.47b), VLDL-C (r = 0.43b) and smaller LDL2 (r = 0.39a). Hepcidin elevation in adolescents with obesity is linked more to inflammation and metabolic alterations than to iron metabolism since the other markers of iron metabolism were not different between groups, except for ferritin. Studies addressing the long-term effects of higher hepcidin levels and their impact on subclinical anemia and iron status are warranted. a p < 0.05; b p < 0.01, c p < 0.001 dp < 0.0001.

Percent Body Fat-Related Disparities of Serum Ferritin on the Risk of Lipid Metabolism Abnormalities in Children and Adolescents

“…Oxidative stress and inflammation caused by obesity may contribute to lipid synthesis and metabolic disorders [ 38 ]. In addition, inflammatory factors secreted by visceral fat (such as IL-6) enter the portal vein circulation and flow directly to the liver, which may stimulate hepatic phospholipid synthesis and cause an increase in ferritin [ 39 , 40 ]. Therefore, metabolic inflammation based on excess fat may be the root cause of obesity and ferritin, increasing the risk of dyslipidemia.…”

Effects of Dried Onion Powder and Quercetin on Obesity-Associated Hepatic Menifestation and Retinopathy

“…A cross-sectional human study indicated that visceral fat is directly associated with liver inflammation and fibrosis, independent of insulin resistance and hepatic steatosis [ 5 ]. However, compared with subcutaneous fat, visceral adipose tissue is more severely infiltrated by macrophages [ 6 ]; hypertrophic adipocytes secrete proinflammatory cytokines, such as interleukin (IL)-6 and tumor necrosis factor (TNF)-α, into circulation and increase inflammation in various organs [ 7 ]. A prospective cross-sectional single-visit study revealed that a high-percentage body fat is associated with dry eye [ 8 ].…”

Association between iron status and incident coronary artery disease: a population based-cohort study

“…Iron metabolism disorders, either deficiency or overload, were associated with increased cardiovascular morbidity and mortality 6 , 7 . Iron overload was positively correlated with the risk factors of cardiovascular disease, such as the risk of metabolic syndrome 8 , insulin resistance (IR) 9 , 10 and new-onset type 2 diabetes mellitus 11 . Excessive iron accumulation accelerates the formation of atherosclerosis through several putative mechanisms.…”