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

We have identified a subset of metabolically obese, but normal weight individuals, with potentially increased risks of developing the metabolic syndrome, despite their normal body mass index. We determined the relationship among body fat distribution, resting metabolic rate (RMR), total body water amount (%TBW), selected gene polymorphism on interleukin-15 receptor-alpha (IL-15Ralpha) and methylenetetrahydrofolate reductase 677C-->T (MTHFR 677C-->T), to distinguish normal weight obese (NWO) from nonobese with a normal metabolic profile and obese individuals. We analysed anthropometric variables, body composition by Dual energy X-ray Absorptiometry (DXA), RMR by indirect calorimetry, %TBW by bioimpedence analysis (BIA), MTHFR 677C-->T and IL-15Ralpha genotypes of 128 clinically healthy Caucasian individuals. We compared a group of female, defined as NWO and characterised by a BMI < or = 25 kg/m(2) and FM > or = 30% with groups of others female, and males, represented by nonobese with a BMI < or = 25 kg/m(2) and FM < or = 30%, and preobese-obese individuals with BMI > or = 25 kg/m(2) and %FM > or = 30%; none of the males was classified as NWO. Significant correlations were found among body fat mass distribution, metabolic variables, percentage of total body water distribution and selected genetic variations. The variables that contributed significantly to the separation of classes were body tissue (Tissue), %TBW, RMR, the volumes of both oxygen (VO2) and carbon dioxide (VCO2). The distribution of MTHFR 677C-->T and IL-15 genotypes was significantly different between classes. Our data highlight that NWO individuals showed a significant relationship between the decrease in the basal metabolism (RMR), body fat mass increasing and total water amount. Possession of wild type homozygotes genotypes regarding IL-15Ralpha cytokine and 677C-->T MTHFR enzyme characterised NWO individuals.
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PMID:Normal Weight Obese syndrome: role of single nucleotide polymorphism of IL-1 5Ralpha and MTHFR 677C-->T genes in the relationship between body composition and resting metabolic rate. 1712 16

Epigallocatechin gallate (EGCG), a bioactive polyphenol in green tea, may augment metabolic and vascular actions of insulin. Therefore, we investigated effects of EGCG treatment to simultaneously improve cardiovascular and metabolic function in spontaneously hypertensive rats (SHR; model of metabolic syndrome with hypertension, insulin resistance, and overweight). In acute studies, EGCG (1-100 microM) elicited dose-dependent vasodilation in mesenteric vascular beds (MVB) isolated from SHR ex vivo that was inhibitable by N(omega)-nitro-L-arginine methyl ester (L-NAME; nitric oxide synthase antagonist) or wortmannin [phosphatidylinositol (PI) 3-kinase inhibitor]. In chronic studies, 9-wk-old SHR were treated by gavage for 3 wk with EGCG (200 mg.kg(-1).day(-1)), enalapril (30 mg.kg(-1).day(-1)), or vehicle. A separate group of SHR receiving L-NAME (80 mg/l in drinking water) was treated for 3 wk with either EGCG or vehicle. Vasodilator actions of insulin were significantly improved in MVB from EGCG- or enalapril-treated SHR (when compared with vehicle-treated SHR). Both EGCG and enalapril therapy significantly lowered systolic blood pressure (SBP) in SHR. EGCG therapy of SHR significantly reduced infarct size and improved cardiac function in Langendorff-perfused hearts exposed to ischemia-reperfusion (I/R) injury. In SHR given L-NAME, beneficial effects of EGCG on SBP and I/R were not observed. Both enalapril and EGCG treatment of SHR improved insulin sensitivity and raised plasma adiponectin levels. We conclude that acute actions of EGCG to stimulate production of nitric oxide from endothelium using PI 3-kinase-dependent pathways may explain, in part, beneficial effects of EGCG therapy to simultaneously improve metabolic and cardiovascular pathophysiology in SHR. These findings may be relevant to understanding potential benefits of green tea consumption in patients with the metabolic syndrome.
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PMID:EGCG, a green tea polyphenol, improves endothelial function and insulin sensitivity, reduces blood pressure, and protects against myocardial I/R injury in SHR. 1722 56

One diagnostic criterion for metabolic syndrome is obesity from the accumulation of visceral fat; others include abdominal circumference and area of visceral fat as measured by computed tomography (CT) at the umbilical level. We evaluated visceral fat using frequency-selective excitation magnetic resonance (MR) imaging SPAIR (spectral attenuation with inversion recovery) water suppression THRIVE (3D T1-high resolution isotropic volume examination). Fifty of 70 slices with 2-mm interval were used to render and measure volume of visceral fat ranging within 10 cm of the umbilicus; the area of visceral fat at the umbilical level was also measured. Imaging was completed using breath hold within 14 s. Image processing was easier than using CT.
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PMID:MR measurement of visceral fat: assessment of metabolic syndrome. 1733 12

In addition to their role in controlling water and salt homeostasis, recent work suggests that aldosterone and mineralocorticoid receptors (MR) may be involved in adipocyte biology. This is of particular relevance given the role of MR as a high-affinity receptor for both mineralocorticoids and glucocorticoids. We have thus examined the effect of aldosterone and MR on white adipose cell differentiation. When cells are cultured in a steroid-free medium, aldosterone promotes acquisition of the adipose phenotype of 3T3-L1 and 3T3-F442A cells in a time-, dose-, and MR-dependent manner. In contrast, late and long-term exposure to dexamethasone inhibits adipocyte terminal maturation. The aldosterone effect on adipose maturation was accompanied by induction of PPARgamma mRNA expression, which was blocked by the MR antagonist spironolactone. Under permissive culture conditions, specific MR down-regulation by siRNAs markedly inhibited 3T3-L1 differentiation by interfering with the transcriptional control of adipogenesis, an effect not mimicked by specific inactivation of the glucocorticoid receptor. These results demonstrate that MR represents an important proadipogenic transcription factor that may mediate both aldosterone and glucocorticoid effects on adipose tissue development. MR thus may be of pathophysiological relevance to the development of obesity and the metabolic syndrome.
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PMID:Pivotal role of the mineralocorticoid receptor in corticosteroid-induced adipogenesis. 1738 39

Modulation by sex hormones of aortic reactivity in rats with the metabolic syndrome (MS) was investigated. The following groups of weanling male Wistar rats were used: control rats (C) received regular tap water while MS rats received 30% sucrose in their drinking water; both had rodent chow for 24 weeks. These two groups were further subdivided into the following four groups: intact (Int), castrated (Cas), castrated plus testosterone (T) and castrated plus estradiol (E). Vascular response of thoracic aortic rings to norepinephrine (NE), acetylcholine (ACh), indomethacin (Indo) and nitro-l-arginine-methyl ester (L-NAME) was investigated. Blood pressure (BP) and serum nitrates and nitrites were measured. BP and serum nitrates and nitrites were modified by castration and treatments with either T or E. Vasoconstriction in Int MS and Cas MS+T aortas was larger than in C and Cas C+T, respectively. Vasodilation in Int MS and Cas MS+T was reduced in comparison with C and Cas C+T, Cas MS and Cas MS+E. Indomethacin decreased vasoconstriction in all groups (P<0.002) but Int C and Cas C+T remained significantly smaller than Int MS and Cas MS+T. l-NAME in NE-contracted vessels induced a significant increase in vasoconstriction, except in Cas C+E rats; the responses of Int MS and Cas MS+T were significantly larger than in Int C and Cas C+T. The results suggest endothelial dysfunction in Int MS and Cas MS+T and a protective effect resulting from castration and castration plus E in MS animals, indicating a sex hormone influence.
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PMID:Modulation of aortic vascular reactivity by sex hormones in a male rat model of metabolic syndrome. 1749 11

Plasma concentrations of free fatty acids are increased in metabolic syndrome, and the increased fatty acids may cause cellular damage via the induction of oxidative stress. The present study was designed to determine whether the increase in fatty acids can modify the free sulfhydryl group in position 34 of albumin (Cys34) and enhance the redox-cycling activity of the copper-albumin complex in high-fat diet-induced obese mice. The mice were fed with commercial normal diet or high-fat diet and water ad libitum for 3 months. The high-fat diet-fed mice developed obesity, hyperlipemia, and hyperglycemia. The plasma fatty acid/albumin ratio also significantly increased in high-fat diet-fed mice. The increased fatty acid/albumin ratio was associated with conformational changes in albumin and the oxidation of sulfhydryl groups. Moreover, an ascorbic acid radical, an index of redox-cycling activity of the copper-albumin complex, was detected only in the plasma from obese mice, whereas the plasma concentrations of ascorbic acid were not altered. Plasma thiobarbituric acid reactive substances were significantly increased in the high-fat diet group. These results indicate that the increased plasma fatty acids in the high-fat diet group resulted in the activated redox cycling of the copper-albumin complex and excessive lipid peroxidation.
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PMID:Fatty acids increase the circulating levels of oxidative stress factors in mice with diet-induced obesity via redox changes of albumin. 1761 29

The glutamatergic system has been implicated in neuropsychiatric disorders, such as schizophrenia, bipolar disorder and Alzheimer's disease, which also have a high prevalence of metabolic syndrome. Treatment with ketamine, a non-competitive glutamate N-methyl-d-aspartic acid (NMDA) receptor antagonist, is known to have paradoxical effects of neuroprotection and neurotoxicity. We investigated gene expression in brain tissue of adult mice treated with ketamine to characterize the expression profiles and to identify the affected metabolic pathways. Adult male mice were treated by a single intraperitoneal (i.p.) injection of either s(+)ketamine (80 mg/kg) or distilled water (as the control). Fifty genes were differentially expressed in ketamine-treated mouse brains compared with control mice using oligonucleotide microarray analysis, and the expression of Troponin T1 (Tnnt1) gene was consistently elevated (2- to 4-fold) (p<0.001). Ketamine-induced Tnnt1 expression was confirmed and characterized using RNA in situ hybridization techniques in paraffin embedded brain tissue sections. Tnnt1 expression was induced in the granule layer of the hippocampus, amygdala, hypothalamus, Purkinje cells of cerebellum (p<0.0001), and cerebral cortex. Tnnt1 gene is known to interact directly with FoxO1, which is involved in multiple peripheral metabolic pathways and central energy homeostasis. Our findings suggest that the induction of Tnnt1 gene expression in adult mouse brains by ketamine may illustrate the genes involved in the metabolic syndromes observed in neuropsychiatric disorders.
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PMID:The expression of Troponin T1 gene is induced by ketamine in adult mouse brain. 1785 Jul 69

Genetically hypertensive rats of the Lyon strain (LH) associate high blood pressure (BP), exaggerated salt-sensitivity, and a metabolic syndrome made of overweight together with increased plasma lipids and insulin/glucose ratio. A genetic mapping study in a large population of F2 rats derived from a cross between hypertensive (LH) and normotensive rats (LN) showed the existence, on chromosome 17, of two clusters of Quantitative Traits Loci (QTLs). The first one was associated to morphological parameters whereas the second influenced blood pressure and plasma lipids level. In order to determine the functional importance of this QTLs, we generated a consomic strain LH-17BN in which the LH chromosome 17 has been fully substituted by a normotensive Brown Norway (BN) one. These LH-17BN, as well as LH and BN male rats of the parental strain were phenotyped. This included radio telemetric measurement of BP during normal and elevated salt intake (1% and then 2% in the drinking water) as well as the determination of morphological, metabolic (triglycerides, cholesterol) and renal (creatinine clearance, proteinuria) parameters. LH-17BN, compared to LH rats, exhibited significant decreases in body weight and blood pressure. Renal functions are improved (decreased of proteinuria). Finally, plasma triglycerides were reduced and reach the level observed in BN rats. In conclusion, the present work demonstrates that, in our model, chromosome 17 contains genes which influence morphology, blood pressure, renal function, and lipid metabolism. Interestingly, chromosome 17 almost completely explains the spontaneous hypertriglyceridemia observed in Lyon Hypertensive rats.
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PMID:[Importance of chromosome 17 in genetically hypertensive rats of the Lyon strain (LH): study of a consomic strain]. 1792 82

A new liquid chromatography-tandem mass spectrometric (LC-MS/MS) approach, based on the precursor ion scanning technique using a triple-stage quadrupole, has been developed to detect free and protein-bound histidine (His) residues modified by reactive carbonyl species (RCS) generated by lipid peroxidation. This approach has been applied to urines from Zucker obese rats, a nondiabetic animal model characterized by obesity and hyperlipidemia, where RCS formation plays a key role in the development of renal and cardiac dysfunction. The immonium ion of His at m/z 110 was used as a specific product ion of His-containing peptides to generate precursor ion spectra, followed by MS2 acquisitions of each precursor ion of interest for structural characterization. By this approach, three novel adducts, which are excreted in free form only, have been identified, two of them originating from the conjugation of 4-hydroxy-trans-2-nonenal (HNE) to His, followed by reduction/oxidation of the aldehyde: His-1,4-dihydroxynonane (His-DHN), His-4-hydroxynonanoic acid (His-HNA), and carnosine-HNE, this last recognized in previous in vitro studies as a new potential biomarker of carbonyl stress. No free His-HNE was found in urines, which was detected only in protein hydrolysates. The same LC-MS/MS method, working in multiple reaction monitoring (MRM) mode, has been developed, validated, and applied to quantitatively profile in Zucker urines both conventional (1,4-dihydroxynonane mercapturic acid, DHN-MA) and the newly identified adducts, except His-HNA. The analytes were separated on a C12 reversed-phase column by gradient elution from 100% A (water containing 5 mM nonafluoropentanoic acid) to 80% B (acetonitrile) in 24 min at a flow rate of 0.2 mL/min and analyzed for quantification in MRM mode by applying the following precursor-to-product ion transitions m/z 322.2 --> 164.1 + 130.1 (DHN-MA), m/z 314.7 --> 268.2 + 110.1 (His-DHN), m/z 312.2 --> 110.1 + 156.0 (His-HNE), m/z 383.1 --> 266.2 + 110.1 (CAR-HNE), m/z 319.2 --> 301.6 + 156.5 (H-Tyr-His-OH, internal standard). Precision and accuracy data, as well as the lower limits of quantification in urine, were highly satisfactory (from 0.01 nmol/mL for CAR-HNE, His-DHN, His-HNE, to 0.075 nmol/mL for DHN-MA). The method, applied to evaluate for the first time the advanced lipoxidation end products profile in urine from obese Zucker rats, an animal model for the metabolic syndrome, has proved to be suitable and sensitive enough for testing in vivo the carbonyl quenching ability of newly developed RCS sequestering agents.
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PMID:HNE Michael adducts to histidine and histidine-containing peptides as biomarkers of lipid-derived carbonyl stress in urines: LC-MS/MS profiling in Zucker obese rats. 1797 57

Our previous studies indicate that prolonged caffeine consumption exacerbates renal failure in nephropathy associated with the metabolic syndrome. Reduced activity of the antioxidant defense system and beneficial effects of antioxidant therapy have been reported in diabetic rats and humans. The purpose of this study was to examine the early renal effects of caffeine consumption and the effects of concomitant antioxidant therapy in young obese, diabetic ZSF1 rats. Eleven-week-old male ZSF1 rats were randomized to drink tap water, caffeine (0.1%), tempol (1 mmol/L), or a solution containing caffeine and tempol for nine weeks. Caffeine significantly reduced body weight and glycosuria (weeks 2-9), improved glucose tolerance (week 9), had no effect on elevated plasma triglycerides, plasma cholesterol (week 9) and blood pressure (week 9), and significantly increased plasma cholesterol level (weeks 5 and 9). Yet, as early as after two weeks, caffeine greatly augmented proteinuria and increased renal vascular resistance (RVR) and heart rate (HR: week 9). Tempol had no effects on metabolic status and development of proteinuria, did not alter caffeine-induced metabolic changes and early proteinuria, and attenuated caffeine-induced increase in HR and RVR. Immunohistochemical analysis revealed significant glomerular and interstitial inflammation, proliferation, and fibrosis in control animals. Caffeine augmented the influx of glomerular and interstitial macrophages (ED1+ cells) influx, glomerular and tubular proliferative response, and glomerular collagen IV content. Tempol abolished the exacerbation of renal inflammation, proliferation, and fibrosis induced by caffeine. In conclusion, in nephropathy associated with the metabolic syndrome, caffeine--most likely through the interaction with adenosine receptors and interference with anti-inflammatory and/or glomerular hemodynamic effects of adenosine--augments proteinuria and stimulates some of the key proliferative mechanisms involved in glomerular remodeling and sclerosis. Tempol does not prevent early renal injury (i.e., proteinuria) induced by caffeine, yet abolishes late renal inflammatory, proliferative, and fibrotic change induced by chronic caffeine consumption in obese ZSF1 rats.
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PMID:Early renal injury induced by caffeine consumption in obese, diabetic ZSF1 rats. 1799 59


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