Relationship between Energy Balance and Circulating Levels of Hepcidin and Ferritin in the Fasted and Postprandial States

Abstract

Markers of iron metabolism are altered in new-onset diabetes, but their relationship with metabolic signals involved in the maintenance of energy balance is poorly understood. The primary aim was to explore the associations between markers of iron metabolism (hepcidin and ferritin) and markers of energy balance (leptin, ghrelin, and the leptin/ghrelin ratio) in both the fasted and postprandial states. These associations were also studied in the sub-groups stratified by diabetes status. This was a cross-sectional study of individuals without disorders of iron metabolism who were investigated after an overnight fast and, in addition, some of these individuals underwent a mixed meal test to determine postprandial responses of metabolic signals. The associations between hepcidin, ferritin, and leptin, ghrelin, leptin/ghrelin ratio were studied using several multiple linear regression models. A total of 76 individuals in the fasted state and 34 individuals in the postprandial state were included. In the overall cohort, hepcidin was significantly inversely associated with leptin (in the most adjusted model, the β coefficient ± SE was −883.45 ± 400.94; p = 0.031) and the leptin/ghrelin ratio (in the most adjusted model, the β coefficient ± SE was −148.26 ± 61.20; p = 0.018) in the fasted state. The same associations were not statistically significant in the postprandial state. In individuals with new-onset prediabetes or diabetes (but not in those with normoglycaemia or longstanding prediabetes or diabetes), hepcidin was significantly inversely associated with leptin (in the most adjusted model, the β coefficient ± SE was −806.09 ± 395.44; p = 0.050) and the leptin/ghrelin ratio (in the most adjusted model, the β coefficient ± SE was −129.40 ± 59.14; p = 0.037). Leptin appears to be a mediator in the link between iron metabolism and new-onset diabetes mellitus. These findings add to the growing understanding of mechanisms underlying the derangements of glucose metabolism.

Alterations of the expression levels of glucose, inflammation, and iron metabolism related miRNAs and their target genes in the hypothalamus of STZ-induced rat diabetes model

“…Our observations correlate with our previous results that the mRNA level of HAMP significantly increased, and FP was eliminated from the plasma membrane in the STZ-treated hypothalamus suggesting iron accumulation. One of the signalling pathways that may contribute to the elevated HAMP level is the BMPR/SMAD [ 66 ], also leptin/LEPR mediated signalling cascade works as a positive regulator of HAMP expression [ 14 ]. We found several miRNAs with altered expression acting as regulators of iron metabolism related genes.…”

“…Iron overload of the human body increases the risk of the establishment of metabolic disorders [ 11 , 12 ]. Recently, it has been revealed that the serum level of the iron regulatory hormone hepcidin and ferritin correlates with the energy balance markers such as leptin [ 13 , 14 ], which functions as a regulator of glucose-sensing neurons in the hypothalamus [ 15 ]. Moreover, insulin influences iron metabolism by affecting the transport of transferrin receptor 1 (TfR1) into the cell membranes and increasing ferritin (FTH) synthesis [ 16 ].…”

The Effect of Treatment on Weight Gain in Iron Deficiency Anemia and Its Association with Ghrelin and Hepcidin Levels

“…In a study conducted in patients with newly diagnosed diabetes mellitus after pancreatitis without overt iron deficiency, a significant negative correlation of hepcidin with leptin, another determinant hormone of energy balance, and with leptin/ghrelin ratio in fasting was shown, but it was reported that it was not correlated with ghrelin (33).…”