Iron homeostasis a new job for macrophages in adipose tissue

The adaptive immune system as a fundamental regulator of. The concept that resident macrophages could contribute to tissue iron homeostasis may have broader implications beyond at. Macrophagederived human resistin exacerbates adipose tissue. Connect with other colleagues in the same hospital or clinic. In some cases, iron uptake by macrophages appears to promote restoration of tissue homeostasis, but macrophage iron overload can also contribute to disease processes.

Our recent data suggests that resident m2like macrophages may play a role in iron metabolism in fat. Jul 11, 2019 in healthy lean adipose tissues, atms exert crucial functions for maintaining immunological and metabolic homeostasis, including immune regulation, efferocytosis, lipid buffering, and angiogenesis. Not much is known about the role of adipose tissue macrophages in tissue homeostasis. Dysfunction of at leads to a wide range of disorders like obesity, insulin resistance, diabetes mellitus, cardiac disorders, tumors and others. Immunologic memory to metabolic cycling alyssa hasty. While macrophages can be divided into the classicallyactivated m1 and the alternativelyactivated m2 phenotype, ascs are characterized by the expression of specific stem cell markers. These exciting findings have opened up a new area of research for our group to assess the impact of macrophage iron handling on adipose tissue homeostasis. Department of molecular physiology and biophysics, vanderbilt university school of medicine, nashville, tn 37232, usa. We also show that exposure to elevated iron via dietary or injection paradigms causes an increase in the specialized iron handling macrophages. Free iron in lung can cause the generation of reactive oxygen species, an important factor in chronic obstructive pulmonary disease copd pathogenesis. Dec 17, 2015 macrophages provide a critical systemic network cells of the innate immune system. Key priorities for future studies will be to determine the role of resident macrophages in tissue iron homeostasis. Iron homeostasis and hemochromatosis flashcards quizlet. These are regulated to ensure homeostasis both systemically in living organisms and within individual cells.

Article in trends in endocrinology and metabolism 262 january 2015 with 76 reads how we measure reads. Specialized transport mechanisms conduct iron across cellular membranes. They derive from hematopoietic precursors and since the early steps of fetal life populate peripheral tissues, a process. Macrophages the key actors in adipose tissue remodeling and. Objective the bidirectional relationship between iron metabolism and glucose homeostasis is increasingly recognized. Meteorinlike is a novel hormone secreted in response to exercise and cold exposure that stimulates eosinophil il4 release and alternative activation of macrophages in adipose. Macrophage functions in lean and obese adipose tissue.

The goal of this paper is not to provide a comprehensive overview of iron metabolism but to offer some basic information on cellular and body iron physiology and pathophysiology, to summarize where the field stands at the present. Kupffer cells are the resident macrophages of the liver. Dietary iron restriction or iron chelation protects from. The source of excess hepcidin appears to be the liver and not adipose tissue. My dissertation explored a role for macrophages in ironhandling of adipose tissue. Obesity was first described as a lowgrade inflammatory condition more than a decade ago.

Merla hubler phd graduate and medical student vanderbilt. Regulation of iron homeostasis in anemia of chronic. They derive from hematopoietic precursors and since the early steps of fetal life populate peripheral tissues, a process continuing throughout adult life. Hubler mj, peterson kr, hasty ah 2015 trends endocrinol metab 262. Obesity has been reported to cause a shift in iron distribution from adipose tissue macrophages to adipocytes, and it has been hypothesized that this could play a causal role in obesityinduced insulin resistance. Iron levels in adipose tissue are important for adipogenesis and adipocyte function.

Among 62 transcripts representing iron homeostasis genes, expression of 30 in adipose tissue were correlated with s i. In contrast, another study showed that adipocytespecific fpn deletion using the. Alyssa hastys profile labnodes the vanderbilt research. Their main function in iron metabolism appears to be as a clearing house for iron from phagocytosed red blood cells. Adipose tissue samples were fixed for 1216 hours at room temperature in formalin fixative sigmaaldrich and embedded in paraffin. Abstracts hubler mj, jeb orr, anders etzerodt, alyssa hasty. Over the past decade, major advances have been made in identifying and characterizing the proteins involved in the transport. Adipose tissue at expansion is accompanied by the infiltration and accumulation of at macrophages atms, as well as a shift in atm polarization. The utility of iron chelators in the management of inflammatory disorders.

For example, elevated scd163 is related to several different diseases and macrophage iron handling is known to be relevant in other tissue. Adipose tissue transferrin and insulin resistance the journal of. In particular, the importance of tissue iron accumulation in inflammation and infection, cancer, genetic, cardiovascular and neurodegenerative diseases continuously increases. Microrna regulated macrophage activation in obesity in. Hasty 1, 3, 1 department of molecular physiology and biophysics, vanderbilt university school of medicine, nashville, tennessee 37232. Current understanding of iron homeostasis the american. In obesity, adipocytes become ironoverloaded concomitant with reduced macrophage iron content. Creative data solutions cds is a vanderbilt shared resource and has extensive experience in providing effective and robust solutions to challenges pertaining to research data using modern informatics and bioinformatics approaches. Over the last decade, understanding of these processes has been enormously enhanced by the molecular cloning and characterization of critical genes, some of which were discovered by investigation of mice and zebrafish with genetic defects leading.

Oct 14, 2015 mounting evidence indicates that the lysosomeautophagy pathway plays a critical role in iron release from ferritin, the main iron storage cellular protein, hence in the distribution of iron to the cells. Iron enriched macrophages in adipose tissue have an iron cycling profile, increased hmox1 expression, and their phenotype is altered in obesity. Because iron overload in adipocytes increases systemic insulin resistance, iron handling by at macrophages may have relevance not only to adipocyte iron. Apr 18, 2017 m2 macrophages activated by cold exposure upregulate thermogenic gene expression in brown adipose tissue and promote fatty acid mobilization in white adipose tissue 48.

In obesity, adipocytes become iron overloaded concomitant with reduced macrophage iron content. These observations were replicated in two independent european ancestry adipose data sets. M1 macrophages in obese adipose tissue induce insulin resistance through mechanisms that involve tolllike receptor 4 and nuclear factor kappa b signaling arkan et al. Tissueresident macrophages are a heterogeneous population of immune cells that fulfill tissuespecific and nichespecific functions. Adipose tissue macrophages atms are assumed to interfere with adipocyte function leading to insulin resistance thereby contributing to the pathogenesis of type 2 diabetes mellitus. Kosteli a, sugaru e, haemmerle g, martin jf, lei j, zechner r, ferrante aw jr. The recent identification of nuclear receptor coactivator 4 as the receptor for ferritin delivery to selective autophagy sheds further light on the understanding of the mechanisms underlying. Biopsied subcutaneous fat was examined for macrophage content by cd68 staining. Weight loss and lipolysis promote a dynamic immune response in murine adipose tissue. The peculiar nature of human adipose tissue macrophages. Hiv dna in circulating monocyte subsets was quantitated by realtime polymerase chain reaction. M2 macrophages activated by cold exposure upregulate thermogenic gene expression in brown adipose tissue and promote fatty acid mobilization in white adipose tissue 48. Ironenriched macrophages in adipose tissue have an ironcycling profile, increased hmox1 expression, and their phenotype is altered in obesity. The mechanism of macrophage iron export is not known, but may again involve ferroportin1 and cp, similar to iron export from hepatocytes.

Fatty acids, which are elevated in obesity, are the main factors that activate these inflammatory pathways in adipocytes and macrophages. Mounting evidence indicates that the lysosomeautophagy pathway plays a critical role in iron release from ferritin, the main iron storage cellular protein, hence in the distribution of iron to the cells. Jul 26, 2015 macrophages are cells of the innate immunity constituting the mononuclear phagocyte system and endowed with remarkable different roles essential for defense mechanisms, development of tissues, and homeostasis. There are over 166 homeostasis careers waiting for you to apply. Concomitantly, the adipocytes become ironoverloaded. Adipose tissue at is a very important endocrine and paracrine organ that regulates other tissues and organs. Our findings provide new insights regarding the role of hepcidin and iron regulation in metabolic homeostasis and adipocyte function, and. Obesity alters adipose tissue macrophage iron content and.

Hepcidin expression is induced by both iron overload and inflammatory stimuli. However, it is only relatively recently that obese individuals have been described with increased macrophage infiltration of adipose tissue, as well. Their role in at dysfunction is nowadays increasingly. Atms comprise tissue resident macrophages present in adipose tissue. A novel role for macrophages in adipose tissue iron homeostasis. Effect of open and closed formula rations on the performance of three strains of laboratory mice.

Hubler is on doximity as a doximity member youll join over a million verified healthcare professionals in a private, secure network. Iron overload, on the other hand, is not so severe as to induce the rapid apoptosis of. Matriptase2 deficiency protects from obesity by modulating iron. We aimed to update the possible influence of iron on insulin. Excessive body iron stores are a risk factor for decreased insulin sensitivity. Iron is needed by all mammalian cells but is toxic in excess. Emerging data suggest that in addition, they have important tissue specific functions that range from clearance. The full text of this article hosted at is unavailable due to technical difficulties. We hypothesize that tissue resident macrophages regulate the supply of iron to adipocytes and thereby contribute to at homeostasis. Most of the iron absorbed from the diet or recycled from hemoglobin is destined for developing erythrocytes. Resident adipose tissue macrophages atms play multiple roles to maintain tissue. A novel role for macrophages in adipose tissue iron.

Elevated serum ferritin and increased cellular iron concentrations are risk factors for diabetes. Isolated adipocytes and macrophages were cultured and the supernatant assayed for secretory products by luminex multiplex cytokine technology. Emerging data suggest that in addition, they have important tissuespecific functions that range from clearance. Adipose tissue transferrin and insulin resistance the. Macrophages provide a critical systemic network cells of the innate immune system. Mfehi adipose tissue macrophages compensate for tissue iron. The field of iron homeostasis is a very active one, and each year thousands of papers are published in this area. Background subcutaneous adipose tissue is a rich source of adipose tissue macrophages and adiposederived stem cells which both play a key role in wound repair. Hasty1,3 1department 2 ofmolecular physiology and biophysics, vanderbilt university school medicine, nashville, tn 37232, usa. Mechanisms linking glucose homeostasis and iron metabolism.

Any iron released from macrophages would first have to be tf bound to be efficiently internalized by adipocytes, thus the. In healthy lean adipose tissues, atms exert crucial functions for maintaining immunological and metabolic homeostasis, including immune regulation, efferocytosis, lipid buffering, and angiogenesis. Full text dibc, a nanochelatingbased nano metalorganic. These range from dedicated homeostatic functions, such as. My dissertation explored a role for macrophages in iron handling of adipose tissue. Read the latest clinical news and earn cmeceu credits. Serum hepcidin is elevated in obese women despite iron depletion, suggesting that it is responding to inflammation rather than iron status. Obesity, insulin resistance, inflammation, adipose tissue macrophages, type 2 diabetes.

Every second bone marrow produces more than 2 million red blood cells. Adipose tissue apart from adipocytes is composed of the stromal vascular fraction svf of cells including preadipocytes, fibroblasts, vascular endothelial cells and variety of immune cells. A decade of progress in adipose tissue macrophage biology. Obesity is a crucial component of peripheral insulin resistance. The recent identification of nuclear receptor coactivator 4 as the receptor for ferritin delivery to selective autophagy sheds further light on the understanding of the. The iron regulatory function of matriptase2 appears to be conserved between humans and mice, as mutations in the human gene encoding matriptase2 tmprss6 have been shown to cause an autosomal recessive form of iron deficiency anemia that is refractory to oral iron therapy. The liverderived acute phase protein hepcidin is the master regulator of iron homeostasis. The role of hiv and monocytesmacrophages in adipose tissue. Increased iron sequestration in alveolar macrophages in. In the context of iron metabolism, macrophages are. Obesity alters adipose tissue macrophage iron content. Glucose metabolism in adipose tissue seems to be affected by both iron deficiency and excess through interaction with adipocyte differentiation, tissue hyperplasia and hypertrophy, release of. Its an amoebalike organism, and its job is to clean.

The main function of macrophages of the reticuloendothelial system in the iron metabolism is to recycle iron from senescent red blood cells. Elucidation the role of mfehi macrophages in adipose tissue iron metabolism. Adipose tissue macrophages, low grade inflammation and. Iron accumulation has been implicated in oxidative stress in other diseases, such as alzheimers and parkinsons diseases, but little is known about iron accumulation in copd. Adipose tissue macrophages atms are the key actors in at remodeling and dysfunction. Sep 18, 20 tissue resident macrophages are a heterogeneous population of immune cells that fulfill tissue specific and nichespecific functions. Fivemicrometer sections cut at 50mm intervals were mounted on charged glass slides, deparaffinized in xylene, and stained for expression of f480 as described elsewhere 43. A possible secondary immune response in adipose tissue during weight cycling. Adipose tissue dysfunction and impaired metabolic health in human obesity. Characterization of adipose tissue macrophages and adipose. Several studies have implicated recruited m1 atms in the metabolic consequences of obesity. We sought to determine if iron content and the expression of. Mfehi adipose tissue macrophages compensate for tissue.

Tissue macrophages are best characterized for their core function of maintenance or restoration of tissue homeostasis by engulfing apoptotic cells, clearing debris, initiation of repair, and. The global rise of obesity, along with the increased risk for complications such as type 2 diabetes, has intensified research on the role of adipose tissue. What have we really learned about macrophage recruitment to adipose tissue. Ccr7 deficiency alters adipose tissue leukocyte populations in mice. Adipose tissue, or body fat, plays an important role in the how the body maintains its metabolism. Several pathways of iron metabolism are modified according to systemic glucose levels, whereas insulin action and secretion are influenced by changes in relative iron excess. A recent study revealed that ferritin light chain ftl mrna and protein levels, and fpn transcripts, were significantly increased.

Macrophages exist in separate types of differentiation, but the nature of atms is largely unknown. A macrophage is a large white blood cell that is an important part of our immune system. New perspectives on the molecular basis of the interaction. The lowstress way to find your next homeostasis job opportunity is on simplyhired. Elevated systemic hepcidin and iron depletion in obese. Macrophages are cells of the innate immunity constituting the mononuclear phagocyte system and endowed with remarkable different roles essential for defense mechanisms, development of tissues, and homeostasis. Nov 28, 2018 concomitantly, the adipocytes become iron overloaded.