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- Aug 24, 2017
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By this time we are all aware that iron should be kept low. In this study iron is involved in insulin resistance, inflammation and fat gain.
Iron homeostasis: a new job for macrophages in adipose tissue?
"men and women in the highest quintile of serum ferritin (Ft) levels – the primary intracellular iron-storage protein that can be released in overload situations (see glossary) – had a relative risk of greater than 3.5 for developing diabetes"
"In fact, this condition is now called dysmetabolic iron overload syndrome (DIOS) [10] and it has even been suggested that serum Ft may serve as a surrogate marker for insulin resistance (IR) [11]. Although inflammatory cytokines can influence iron storage in various cell types, studies have shown that the link between elevated iron and obesity/diabetes is independent of inflammation"
"iron depletion by phlebotomy, even in healthy subjects, has been shown to improve insulin sensitivity"
"iron overload of adipocytes also contributes to local and systemic IR" So it would seem that when losing weight, someone can easily flood their system with iron, if iron stores are high.
"Despite the link between iron-overload and obesity mentioned above, inflammation in obesity also leads to iron-deficient anemia [20]. Linking obesity with both tissue iron overload and iron deficient anemia"
Iron is recycled by the macrophages, and CD163, which is a scavenger receptor on the macrophages, binds and endocytoses haptoglobin-hemoglobin (Hp-Hb) complexes to prevent hemoglobin-induced toxicity.
Inflammation removes the CD163 from the macrophages and forms soluble CD163 (sCD163), and sCD163 is therefore sometimes used as a biomarker of tissue macrophage activation.
"CD163 expression on tissue macrophages is increased in autoimmune diseases such as rheumatoid arthritis, multiple sclerosis, Crohn’s disease, and celiac disease and it is also highly expressed on tumor-associated macrophages.
sCD163 is elevated in obesity, diabetes, and gestational diabetes"
"chronic inflammation-induced hepcidin expression, increased serum Ft reflective of tissue iron overload occurs concomitantly with anemia." Hepcidin inhibits iron absorption, and release from tissue liver, resulting in overload and anemia at the same time. Adipose tissue, macrophages and inflammation increase hepcidin.
"iron chelation, result in iron depletion and antiadipogenic effects in human AT explants"
Reducing iron can reduce fat gain.
Iron also stimulates lipolysis by increasing lipid peroxidation end product 4-hydroxy-2-nonenal (4-HNE). Excess iron combined with PUFAs can easily lead to excess lipolysis and elevated free fatty acids in the blood leading to dyslipidemia and glucose intolerance.
Nitric oxide and endotoxins increase iron retention.
IL-4 and IL-10 has been shown to induce M2-like macrophage polarization and inhibits NO-induced iron retention. Saturated fat, especially stearic acid, increases IL-4, IL-10 and M2 polarization, thus would improve iron handling.
"serum Ft is an indication of systemic iron-overload. However, this may be an oversimplification, as the site of iron-overload cannot be determined simply from measuring serum Ft. It is clear that many different metabolic tissues, including pancreas, liver, and AT, may be relevant to the metabolic perturbations associated with iron-overload"
Iron homeostasis: a new job for macrophages in adipose tissue?
"men and women in the highest quintile of serum ferritin (Ft) levels – the primary intracellular iron-storage protein that can be released in overload situations (see glossary) – had a relative risk of greater than 3.5 for developing diabetes"
"In fact, this condition is now called dysmetabolic iron overload syndrome (DIOS) [10] and it has even been suggested that serum Ft may serve as a surrogate marker for insulin resistance (IR) [11]. Although inflammatory cytokines can influence iron storage in various cell types, studies have shown that the link between elevated iron and obesity/diabetes is independent of inflammation"
"iron depletion by phlebotomy, even in healthy subjects, has been shown to improve insulin sensitivity"
"iron overload of adipocytes also contributes to local and systemic IR" So it would seem that when losing weight, someone can easily flood their system with iron, if iron stores are high.
"Despite the link between iron-overload and obesity mentioned above, inflammation in obesity also leads to iron-deficient anemia [20]. Linking obesity with both tissue iron overload and iron deficient anemia"
Iron is recycled by the macrophages, and CD163, which is a scavenger receptor on the macrophages, binds and endocytoses haptoglobin-hemoglobin (Hp-Hb) complexes to prevent hemoglobin-induced toxicity.
Inflammation removes the CD163 from the macrophages and forms soluble CD163 (sCD163), and sCD163 is therefore sometimes used as a biomarker of tissue macrophage activation.
"CD163 expression on tissue macrophages is increased in autoimmune diseases such as rheumatoid arthritis, multiple sclerosis, Crohn’s disease, and celiac disease and it is also highly expressed on tumor-associated macrophages.
sCD163 is elevated in obesity, diabetes, and gestational diabetes"
"chronic inflammation-induced hepcidin expression, increased serum Ft reflective of tissue iron overload occurs concomitantly with anemia." Hepcidin inhibits iron absorption, and release from tissue liver, resulting in overload and anemia at the same time. Adipose tissue, macrophages and inflammation increase hepcidin.
"iron chelation, result in iron depletion and antiadipogenic effects in human AT explants"
Reducing iron can reduce fat gain.
Iron also stimulates lipolysis by increasing lipid peroxidation end product 4-hydroxy-2-nonenal (4-HNE). Excess iron combined with PUFAs can easily lead to excess lipolysis and elevated free fatty acids in the blood leading to dyslipidemia and glucose intolerance.
Nitric oxide and endotoxins increase iron retention.
IL-4 and IL-10 has been shown to induce M2-like macrophage polarization and inhibits NO-induced iron retention. Saturated fat, especially stearic acid, increases IL-4, IL-10 and M2 polarization, thus would improve iron handling.
"serum Ft is an indication of systemic iron-overload. However, this may be an oversimplification, as the site of iron-overload cannot be determined simply from measuring serum Ft. It is clear that many different metabolic tissues, including pancreas, liver, and AT, may be relevant to the metabolic perturbations associated with iron-overload"