Abstract
BackgroundHereditary hemochromatosis (HH) is an autosomal recessive genetic disorder with increased intestinal iron absorption and therefore iron Overload. iron overload leads to increased levels of toxic non-transferrin bound iron which results in oxidative stress and lipid peroxidation. The impact of iron on lipid metabolism is so far not fully understood. The aim of this study was to investigate lipid metabolism including lipoproteins (HDL, LDL), neutral (triglycerides, cholesterol) and polar lipids (sphingo- and phospholipids), and PNPLA3 polymorphism (rs738409/I148M) in HH.MethodsWe conducted a cohort study of 54 subjects with HH and 20 healthy subjects. Patients were analyzed for their iron status including iron, ferritin, transferrin and transferrin saturation and serum lipid profile on a routine follow-up examination.ResultsHH group showed significantly lower serum phosphatidylcholine (PC) and significantly higher phosphatidylethanolamine (PE) compared to healthy control group. The ratio of PC/PE was clearly lower in HH group indicating a shift from PC to PE. Triglycerides were significantly higher in HH group. No differences were seen for HDL, LDL and cholesterol. Hepatic steatosis was significantly more frequent in HH. PNPLA3 polymorphism (CC vs. CG/GG) did not reveal any significant correlation with iron and lipid parameters including neutral and polar lipids, grade of steatosis and fibrosis.ConclusionOur study strengthens the hypothesis of altered lipid metabolism in HH and susceptibility to nonalcoholic fatty liver disease. Disturbed phospholipid metabolism may represent an important factor in pathogenesis of hepatic steatosis in HH.
Highlights
Hereditary hemochromatosis (HH) is an autosomal recessive genetic disorder with increased intestinal iron absorption and iron Overload. iron overload leads to increased levels of toxic non-transferrin bound iron which results in oxidative stress and lipid peroxidation
The two groups were significantly different in serum iron contents (Healthy subjects vs. HH: transferrin 2.1 vs. 1.8 g/l, p < 0.0001, transferrin saturation 26.0% vs. 70.1%, p < 0.0001, iron 13.5 μmol/l vs. 31.8 μmol/l, p < 0.0001, ferritin 133.0 μ/l vs. 261.0 μ/l, p = 0.02)
Significant more hepatic steatosis in HH compared to the control group was found (p < 0.0001)
Summary
Hereditary hemochromatosis (HH) is an autosomal recessive genetic disorder with increased intestinal iron absorption and iron Overload. iron overload leads to increased levels of toxic non-transferrin bound iron which results in oxidative stress and lipid peroxidation. Hereditary hemochromatosis (HH) is an autosomal recessive genetic disorder with increased intestinal iron absorption which leads to iron overload and to tissue damage and functional impairment of organs like liver, pancreas, and heart [1,2,3]. Animal models with dietary iron overload showed marked changes in plasma lipid profiles with elevated triglycerides and total cholesterol, decreased high-density lipoprotein (HDL), altered composition of very-low density lipoprotein (VLDL) and hepatic sterol metabolism [6,7,8]. Iron overload increased intracellular lipid droplets, which was associated with increased phosphatidylserine (PS) in the outer leaflet of the plasma membrane [11] This alteration was observed in membranes of erythrocytes in HH [12]. In rat livers excess dietary iron intake causes prosteatotic state which was associated with a decrease in ω-3 long-chain polyunsaturated fatty acid (PUFA) levels and an upregulation of the expression of lipogenic transcription factors [16]
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