Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0948265 (metabolic syndrome)
 24,271 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vitamin D has an essential role in calcium metabolism and bone health. Vitamin D3 or cholecalciferol is synthesized from 7-dehydrocholesterol or provitamin D3, by sunlight ultraviolet radiation to the skin. 7-dehydrocholesterol is subsequently hydroxylated in the liver and then in the kidney to produce 1,25-(OH)2D3, the active metabolite that binds to specific receptors (VDR) in target tissues, mainly bone and intestine. Other tissues, such as the immune and cardiovascular system, have also VDR. Vitamin D deficiency can induce rickets in children and osteomalacia and osteoporosis in adults. A possible inverse association between vitamin D levels and the prevalence of metabolic syndrome has been proposed. Vitamin D deficiency increases the risk of type 1 diabetes, insulin resistance, and hypertension, key components of this syndrome. However, other studies have not confirmed this association. Further clinical and experimental studies are needed to ascertain the role of vitamin D in metabolic syndrome.
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PMID:[Association between vitamin D deficiency and metabolic syndrome]. 2127 81

Vitamin D status has been associated with obesity, metabolic syndrome and several cancers including colon and breast. Since adipocytes express VDR and obesity is a known risk factor for cancer, vitamin D actions in adipose tissue may contribute to its cancer protective effects. In the mammary gland, signaling from adipocytes to epithelial cells is necessary for breast cancer initiation, but the impact of vitamin D on this cross-talk is unclear. To examine the role of VDR in adipose tissue, particularly in the context of the mammary gland, we crossed Vdr-flox mice with Fabp4-cre mice to generate mice with adipose-specific Vdr deletion (termed CVF mice). CVF mice and Fabp4-cre control mice (termed CN1 mice) were reared on high calcium "rescue" diets (for comparison to global VDRKO mice) or on high fat diets (to stimulate adiposity). Vdr expression was significantly reduced in adipose tissue of CVF mice compared to CN1 mice. In contrast to global VDRKO mice (which exhibit adipose atrophy), female CVF mice exhibited higher growth rates and increased visceral fat pad weight compared to control mice. Expression of Ucp1 and Pparg were elevated in white adipose tissue of CVF mice supporting these genes as Vdr targets in mature adipocytes. Adipose-specific Vdr deletion did not impair glucose tolerance or alter the weight of brown adipose tissue, liver, pancreas or bone in response to high fat feeding. In contrast to the effect of adipose-specific Vdr deletion on visceral fat pads, the weight of the subcutaneous (mammary) fat pad was not increased in high fat fed CVF female mice compared to control mice. Quantitative analysis of mammary ductal development on whole mounts and H&E stained sections indicated that adipose-deletion of Vdr significantly enhanced mammary epithelial density and branching. Collectively, these data support the hypothesis that Vdr in mature adipocytes alters the metabolic response to high fat diets and exerts anti-proliferative effects on the mammary epithelium.
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PMID:Adipose-specific Vdr deletion alters body fat and enhances mammary epithelial density. 2642 95

Vitamin D (VitD), a lipid-soluble hormone, is able to regulate the transcription of many genes through vitamin D receptor (vitD receptor-VDR). It has been shown that VitD deficiency is associated with obesity, characterized by a low degree inflammatory state, which contribute to the pathogeny of metabolic syndrome and type 2 diabetes mellitus. VitD deficiency is a public health problem, at the same time the global prevalence of obesity and cardiovascular diseases is continuously growing. Evidence from recent studies on animal models suggest that VitD or VDR deficiency promotes cardiomyocyte hypertrophy, which can be one of the mechanisms for increasing cardiovascular risk. The heart is one of the target organs of action for VitD, because VDR is expressed in cardiomyocytes. Also, previous in vitro studies have shown that VitD is able to inhibit the production of monocyte chemotactic factors (MCP-1) and other pro-inflammatory mediators in human preadipocytes and mature adipocytes. Inflammation is an important factor in the pathogenesis of atherosclerosis. In obesity there are not known data about correlations between plasma levels of VitD and VDR expression in the subcutaneous fat tissue, epicardial visceral adipose tissue, and in particular in myocardium. Also, there are still no studies to test VDR expression in myocardial cells and to investigate the results of dietary VitD supplementation on the expression of VDR in the epicardial adipose tissue and myocardium.
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PMID:VITAMIN D AND TISSULAR EXPRESSION OF VITAMIN D RECEPTOR IN OBESITY. 2748 26

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the world. NAFLD is known to be associated with obesity, type 2 diabetes, metabolic syndrome and increased cardiovascular events: for these reasons, it is becoming a global public health problem and represents an important challenge in terms of prevention and treatment. The mechanisms behind the pathogenesis of NAFLD are multiple and have not yet been completely unraveled; consequently, at moment there are not effective treatments. In the past few years a large body of evidence has been assembled that attributes an important role in hepatic aberrant fat accumulation, inflammation and fibrosis, to the vitamin D/vitamin D receptor (VD/VDR) axis, showing a strong association between hypovitaminosis D and the diagnosis of NAFLD. However, the data currently available, including clinical trials with VD supplementation, still provides a contrasting picture. The purpose of this editorial is to provide an overview of recent advances in the pathogenesis of NAFLD in relation to VD/VDR. Based on recent data from literature, we focused in particular on the hypothesis that VDR itself, independently from its traditional ligand VD, may have a crucial function in promoting hepatic fat accumulation. This might also offer new possibilities for future innovative therapeutic approaches in the management of NAFLD.
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PMID:Overview of studies of the vitamin D/vitamin D receptor system in the development of non-alcoholic fatty liver disease. 3155 5

The purpose of this work was to assess the influence of selected CNR1, MC4R, LEP, FTO and VDR FOKI gene polymorphisms on blood and urine concentration markers of lead, cadmium and arsenic in a population directly exposed to these metals. Eighty-five people exposed to lead, arsenic and cadmium were qualified to take part in the study. Standard urine samples and 25mL of venous blood from each worker were collected to assay basic laboratory and toxicological markers as well as selected single nucleotide polymorphisms (SNPs) within CNR1-cannabinoid receptor 1 gene (rs806368, rs806381, rs1049353, rs12720071), MC4R-melanocortin 4 receptor gene (rs17782313), LEP-leptin promoter gene (rs7799039), FTO-alpha-ketoglutarate-dependent dioxygenase gene (rs9939609) and VDR-vitamin D receptor (rs10735810) genes. It appeared that, except for the MC4R SNP, all the other polymorphisms were found to be associated with various laboratory parameters. Arsenic concentration in urine was associated with all four CNR1 and LEP SNPs, while cadmium concentration in blood was affected by the VDR polymorphism. Moreover, some significant relationships were also observed between CNR1 rs1049353 and FTO rs9939609 gene variants and markers of lead exposure. These results imply SNPs within genes coding for proteins involved in development of metabolic syndrome may be of prognostic value for persons directly exposed to lead, cadmium and arsenic.
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PMID:The Relationship Between Selected CNR1, MC4R, LEP, FTO and VDR Gene Polymorphisms and Several Basic Toxicological Parameters Among Persons Occupationally Exposed to Arsenic, Cadmium and Lead. 3227 84