Adipocyte iron regulates leptin and food intake.

Dietary iron supplementation is associated with increased appetite. Here, we investigated the effect of iron on the hormone leptin, which regulates food intake and energy homeostasis. Serum ferritin was negatively associated with serum leptin in a cohort of patients with metabolic syndrome. Moreover, the same inverse correlation was observed in mice fed a high-iron diet. Adipocyte-specific loss of the iron exporter ferroportin resulted in iron loading and decreased leptin, while decreased levels of hepcidin in a murine hereditary hemochromatosis (HH) model increased adipocyte ferroportin expression, decreased adipocyte iron, and increased leptin. Treatment of 3T3-L1 adipocytes with iron decreased leptin mRNA in a dose-dependent manner. We found that iron negatively regulates leptin transcription via cAMP-responsive element binding protein activation (CREB activation) and identified 2 potential CREB-binding sites in the mouse leptin promoter region. Mutation of both sites completely blocked the effect of iron on promoter activity. ChIP analysis revealed that binding of phosphorylated CREB is enriched at these two sites in iron-treated 3T3-L1 adipocytes compared with untreated cells. Consistent with the changes in leptin, dietary iron content was also directly related to food intake, independently of weight. These findings indicate that levels of dietary iron play an important role in regulation of appetite and metabolism through CREB-dependent modulation of leptin expression.

Therapeutic management of neonatal hemochromatosis: report of four cases and literature review.

Neonatal hemochromatosis (NH) is a rare disease of iron metabolism that starts at intrauterine period causing liver failure and extrahepatic siderozis. The etiology of NH has not been understood exactly, yet it is accepted that a maternofetal alloimmune disorder that leads to liver failure in fetus causes the illness. The prognosis of NH is generally bad and death is inevitable if left untreated. The efficiency of chelation-antioxidant coctail used in medical treatment is between 10% and 20% and these patients frequently need liver transplantation. In our study, we presented four newborn cases diagnosed as NH and treated medically. Of the four patients, one died of pulmonary hemorrhage and another died of multiorgan failure in the first week of hospitalization. The other two patients' clinical status and laboratory parameters recovered with medical treatment. However, since liver transplantation was not carried out, one of these patients died at the age of two and a half months and the other at eighth month due to sepsis. In this study, we would like to emphasize the importance of early liver transplantation in patients recovered with medical treatment.

Treatment of neonatal hemochromatosis with exchange transfusion and intravenous immunoglobulin.

OBJECTIVE: To determine if immunomodulatory treatment including intravenous immunoglobulin (IVIG) can favorably affect survival in neontatal hemochromatosis (NH) diagnosed postnatally because it can effectively prevent occurrence of NH when applied during gestations at risk. STUDY DESIGN: We treated 16 newborn infants with liver failure due to NH with high-dose IVIG, in combination with exchange transfusion in 13 (ET/IVIG), and compared the outcome with 131 historical controls treated conventionally. RESULTS: The severity of liver disease as estimated by prothrombin time was similar in the subjects receiving ET/IVIG and the historical controls, and the medical therapy was equivalent with the exception of the ET/IVIG therapy. Twelve subjects (75%) had good outcome, defined as survival without liver transplantation, whereas good outcome was achieved in only 17% (23/131) of historical control patients (P < .001). Four subjects died, 2 without and 2 after liver transplant. Survivors were discharged 6 to 90 days after receiving ET/IVIG therapy, and those followed for more than 1 year are within normal measures for growth, development, and liver function. CONCLUSIONS: Immune therapy with ET/IVIG appears to improve the outcome and reduce the need for liver transplantation in patients with NH.

Hemochromatosis and dietary iron supplementation: implications from US mortality, morbidity, and health survey data.

Trends in the mortality rates, morbidity rates, and hematologic screening parameters for hemochromatosis in the United States over the past 20 years were examined to assess whether dietary iron supplementation is a precipitating factor for hemochromatosis. From 1968 through 1987, there was an increase in the overall hemochromatosis mortality rates attributable to white women. From 1979 through 1987, the hospitalization rates for hemochromatosis ranged from 4 to 13 per 100,000 persons in Medicaid data (1984) and the National Hospital Discharge Survey (1979-1987) and are similar to estimates in the literature from 1955. Although the iron nutritional status of persons under 55 years of age increased from the first to the second National Health and Nutrition Examination Survey, there was no corresponding increase at the 95th percentile in the hemochromatosis screening parameters--serum iron concentration and transferrin saturation. A hypothetical scenario was used to examine the progression from homozygous gene frequency to phenotypic expression. It is concluded that clinical hemochromatosis is rarer than prevalence estimates of 100 to 500 per 100,000 persons predicted by gene frequency. In addition, there is no strong evidence of an increase in hemochromatosis from mortality, morbidity, or health survey data, which implies that dietary iron supplementation begun in 1940 has not accelerated manifestations of hemochromatosis. Any increase in hemochromatosis since iron fortification can probably be attributed to accuracy in diagnosis and enhanced awareness of the disease by physicians rather than to environmental factors.