Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0311277 (abdominal obesity)
 2,792 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hepcidin plays a key role in regulating iron metabolism by blocking iron efflux from macrophages and enterocytes. Hepcidin is synthesized primarily in the liver, and its expression is increased by iron overload and inflammation. Obesity is associated with chronic inflammation as well as poor iron status. Central obesity causes adipocyte hypoxia resulting in chronic inflammation. Therefore, the objective of the present study was to determine if adipocyte hypoxia and associated inflammation signal hepatocyte hepcidin expression. The effect of adipocyte hypoxia on hepcidin expression was modeled using a 3T3-L1 adipocyte/Huh7 hepatocyte co-culture model. Adipocytes were cultured at either standard conditions (19% O2) or hypoxic conditions (1% O2). Compared to standard conditions, hypoxic 3T3-L1 cells had significantly higher IL-6 and leptin expression. Treatment of Huh7 cells with media from hypoxic or LPS-treated 3T3-L1 adipocytes significantly increased hepcidin promoter activity and mRNA compared to cells treated with normoxic 3T3-L1 media or control media. When the hepcidin STAT3 binding site was mutated, promoter activation by hypoxic media was abrogated. These data suggest that adipocyte hypoxia (a feature of central obesity) may increase hepcidin expression and plays a role in the association between obesity and poor iron status.
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PMID:Adipocyte hypoxia increases hepatocyte hepcidin expression. 2118 Dec 93

Macrophages and their counterparts in the central nervous system, the microglia, detect and subsequently clear microbial pathogens and injured tissue. These phagocytic cells alter and adapt their phenotype depending on their prime activity, i.e., whether they participate in acute defence against pathogenic organisms ('M1'-phenotype) or in clearing damaged tissues and performing repair activities ('M2'-phenotype). Stimulation of pattern recognition receptors by viruses (vaccines), bacterial membrane components (e.g., LPS), alcohol, or long-chain saturated fatty acids promotes M1-polarization. Vaccine or LPS administration to healthy human subjects can result in sickness symptoms and low mood. Alcohol abuse and abdominal obesity are recognized as risk factors for depression. In the M1-polarized form, microglia and macrophages generate reactive oxygen and nitrogen radicals to eradicate microbial pathogens. Inadvertently, also tetrahydrobiopterin (BH4) may become oxidized. This is an irreversible reaction that generates neopterin, a recognized biomarker for depression. BH4 is a critical cofactor for the synthesis of dopamine, noradrenaline, and serotonin, and its loss could explain some of the symptoms of depression. Based on these aspects, the suppression of M1-polarization would limit the inadvertent catabolism of BH4. In the current review, we evaluate the evidence that antidepressant treatments (monoamine reuptake inhibitors, PDE4 inhibitors, lithium, valproate, agomelatine, tianeptine, electroconvulsive shock, and vagus nerve stimulation) inhibit LPS-induced microglia/macrophage M1-polarization. Consequently, we propose that supplementation with BH4 could limit the reduction in central monoamine synthesis and might represent an effective treatment for depressed mood.
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PMID:Antidepressant therapies inhibit inflammation and microglial M1-polarization. 2710 21