Pre-emptive iron supplementation prevents myocardial iron deficiency and attenuates adverse remodelling after myocardial infarction.

Aims: Heart failure (HF) after myocardial infarction (MI) is a major cause of morbidity and mortality. We sought to investigate the functional importance of cardiac iron status after MI and the potential of pre-emptive iron supplementation in preventing cardiac iron deficiency (ID) and attenuating left ventricular (LV) remodelling.

Methods And Results: MI was induced in C57BL/6J male mice by left anterior descending coronary artery ligation.

In vivo adenine base editing reverts C282Y and improves iron metabolism in hemochromatosis mice.

Hemochromatosis is one of the most common inherited metabolic diseases among white populations and predominantly originates from a homozygous C282Y mutation in the HFE gene. The G > A transition at position c.845 of the gene causes misfolding of the HFE protein, ultimately resulting in its absence at the cell membrane.

Cardiac iron concentration in relation to systemic iron status and disease severity in non-ischaemic heart failure with reduced ejection fraction.

Aims: Low cardiac iron levels promote heart failure in experimental models. While cardiac iron concentration (CI) is decreased in patients with advanced heart failure with reduced ejection fraction (HFrEF), CI has never been measured in non-advanced HFrEF. We measured CI in left ventricular (LV) endomyocardial biopsies (EMB) from patients with non-advanced HFrEF and explored CI association with systemic iron status and disease severity.

The diabetes gene Zfp69 modulates hepatic insulin sensitivity in mice.

Aims/hypothesis: Zfp69 was previously identified by positional cloning as a candidate gene for obesity-associated diabetes. C57BL/6J and New Zealand obese (NZO) mice carry a loss-of-function mutation due to the integration of a retrotransposon. On the NZO background, the Zfp69 locus caused severe hyperglycaemia and loss of beta cells.

Hepatic trans-Golgi action coordinated by the GTPase ARFRP1 is crucial for lipoprotein lipidation and assembly.

The liver is a major organ in whole body lipid metabolism and malfunctioning can lead to various diseases including dyslipidemia, fatty liver disease, and type 2 diabetes. Triglycerides and cholesteryl esters are packed in the liver as very low density lipoproteins (VLDLs). Generation of these lipoproteins is initiated in the endoplasmic reticulum and further maturation likely occurs in the Golgi.

Trans-Golgi proteins participate in the control of lipid droplet and chylomicron formation.

LDs (lipid droplets) carrying TAG (triacylglycerol) and cholesteryl esters are emerging as dynamic cellular organelles that are generated in nearly every cell. They play a key role in lipid and membrane homoeostasis. Abnormal LD dynamics are associated with the pathophysiology of many metabolic diseases, such as obesity, diabetes, atherosclerosis, fatty liver and even cancer.

The GTPase ARFRP1 controls the lipidation of chylomicrons in the Golgi of the intestinal epithelium.

The uptake and processing of dietary lipids by the small intestine is a multistep process that involves several steps including vesicular and protein transport. The GTPase ADP-ribosylation factor-related protein 1 (ARFRP1) controls the ARF-like 1 (ARL1)-mediated Golgi recruitment of GRIP domain proteins which in turn bind several Rab-GTPases. Here, we describe the essential role of ARFRP1 and its interaction with Rab2 in the assembly and lipidation of chylomicrons in the intestinal epithelium.

Erythropoietin regulates intestinal iron absorption in a rat model of chronic renal failure.

Erythropoietin is produced by the kidney and stimulates erythropoiesis; however, in chronic renal disease its levels are reduced and patients develop anemia that is treatable with iron and recombinant hormone. The mechanism by which erythropoietin improves iron homeostasis is still unclear, but it may involve suppression of the iron regulatory peptide hepcidin and/or a direct effect on intestinal iron absorption. To investigate these possibilities, we used the well-established 5/6th nephrectomy rat model of chronic renal failure with or without human recombinant erythropoietin treatment.

Oncostatin M is a potent inducer of hepcidin, the iron regulatory hormone.

Erythropoietic activity is known to affect iron homeostasis through regulation of the liver iron regulatory hormone hepcidin. To identify new factors secreted by the erythroblasts that could influence hepcidin synthesis, we set up a coculture model. HuH7 hepatoma cells cocultured with primary human erythroblasts or erythroleukemic UT7 cells presented a 20- to 35-fold increase of hepcidin gene expression.

Hepcidin decreases iron transporter expression in vivo in mouse duodenum and spleen and in vitro in THP-1 macrophages and intestinal Caco-2 cells.

Hepcidin is thought to control iron metabolism by interacting with the iron efflux transporter ferroportin. In macrophages, there is compelling evidence that hepcidin directly regulates ferroportin protein expression. However, the effects of hepcidin on intestinal ferroportin levels are less conclusive.

Activated macrophages induce hepcidin expression in HuH7 hepatoma cells.

Background: Hepcidin is an iron regulatory peptide produced by the liver in response to inflammation and elevated systemic iron. Recent studies suggest that circulating monocytes and resident liver macrophages--Küpffer cells--may influence both basal and inflammatory expression of hepcidin.

Design And Methods: We used an in vitro co-culture model to investigate hepatocyte hepcidin regulation in the presence of activated THP1 macrophages.

Leptin increases the expression of the iron regulatory hormone hepcidin in HuH7 human hepatoma cells.

Obesity is a major global health problem and is associated with low-grade inflammation and, in a number of cases, poor iron status. We speculated that the adipokine leptin might play a role in regulating iron metabolism in the overweight population because it shares a number of common biological features with IL-6, a major factor in the development of the anemia of chronic disease via its stimulatory actions on the production and release of the iron regulatory hormone hepcidin. To test this hypothesis, we exposed HuH7 human hepatoma cells to leptin and measured hepcidin mRNA expression by quantitative PCR.