Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Insulin resistance is commonly associated with hypertension, a condition that causes vascular disease in people with obesity and type 2 diabetes. The mechanisms linking hypertension and insulin resistance are poorly understood. To determine whether respiratory uncoupling can prevent insulin resistance-related hypertension, we crossed transgenic mice expressing uncoupling protein 1 (UCP1) in skeletal muscle with lethal yellow (A(y)/a) mice, genetically obese animals known to have elevated blood pressure. Despite increased food intake, UCP-A(y)/a mice weighed less than their A(y)/a littermates. The metabolic rate was higher in UCP-A(y)/a mice than in A(y)/a mice and did not impair their ability to alter oxygen consumption in response to temperature changes, an adaptation involving sympathetic nervous system activity. Compared with their nontransgenic littermates, UCP-A(y)/a mice had lower fasting insulin, glucose, triglyceride, and cholesterol levels and were more insulin sensitive. Blood pressure, serum leptin, and urinary catecholamine levels were also lower in uncoupled mice. Independent of sympathetic nervous system activity, low-dose peripheral leptin infusion increased blood pressure in UCP-A(y)/a mice but not in their A(y)/a littermates. These data indicate that skeletal muscle respiratory uncoupling reverses insulin resistance and lowers blood pressure in genetic obesity without affecting thermoregulation. The data also suggest that uncoupling could decrease the risk of atherosclerosis in type 2 diabetes.
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PMID:Respiratory uncoupling lowers blood pressure through a leptin-dependent mechanism in genetically obese mice. 1206 92

The 5-10% body weight loss often leads to amelioration or cure of hypertension and diabetes mellitus in obese patients. But, the effect of diet therapy on obese patients differs in each individual because of the differences in energy expenditure, such as the resting metabolic rate (RMR). We have recently reported that obese Japanese with the missense mutation (Trp64Arg) of the beta 3-adrenergic receptor (beta 3-AR) gene and/or the uncoupling protein 1 (UCP1) gene mutation (A-3826G) have difficulties in weight loss by the reducing RMR, while Japanese with beta 2-AR gene mutation (Arg16Gly) have an under-weight condition through increased RMR. Here I introduce the importance of tailor-made diet therapy to improve obesity based on analysis of gene polymorphisms and in order to maintain this tailor-made diet therapy, I emphasize that the stress-management therapy should be needed to remove mental problems which caused obesity.
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PMID:[The knack of treatment for obese patients with hypertension and diabetes mellitus: combined the newest tailor-made diet therapy with the usual stress-management therapy]. 1287 68

A range of epidemiological and experimental studies have indicated that suboptimal nutrition at different stages of gestation is associated with an increased prevalence of adult hypertension, cardiovascular disease, and obesity. The timing of prenatal nutrient restriction is important in determining postnatal outcomes-including obesity. The present study, aimed to determine the extent to which fetal adiposity and expression of the key thermogenic protein, uncoupling protein (UCP)1, are altered by restriction of maternal nutrient intake imposed during four different periods, starting from before conception. Maternal nutrient intake was restricted from 60 days before until 8 days after mating (periconceptional nutrient restriction; R-C), from 60 days before mating and throughout gestation (R-R), from 8 days gestation until term (C-R), or from 115 days gestation until term. Fetal perirenal adipose tissue (PAT) was sampled near to term at approximately 143 days. UCP1 mRNA, but not protein, abundance in PAT was increased in fetuses in the R-R group (C-C 63 +/- 18; R-C 83 +/- 43; C-R 103 +/- 38; R-R 167 +/- 50 arbitrary units (P < 0.05)). In contrast, the abundance of UCP1 mRNA, but not protein, in fetal PAT was decreased when maternal nutrition was restricted from 115 days gestation. The major effect of maternal nutrient restriction on adipose tissue deposition occurred in the C-R group, in which the proportion of fetal fat was doubled, whereas maternal nutrient restriction from 115 days gestation reduced fetal fat deposition. In conclusion, there are differential effects of maternal and therefore fetal nutrient restriction on UCP1 mRNA expression and fetal fat mass and these effects are dependent on the timing and duration of nutrient restriction.
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PMID:Nutritional manipulation of fetal adipose tissue deposition and uncoupling protein 1 messenger RNA abundance in the sheep: differential effects of timing and duration. 1505 67

The pharmacological treatment of obesity should be considered when cannot be achieved a 10% weight loss with diet therapy and physical activity. The drugs effective in obesity treatment may act by different mechanisms such as reduction in food intake, inhibition of fat absorption, increase of thermogenesis and stimulation of adipocyte apoptosis. At present, we only have two marketed drugs for obesity treatment. Sibutramine is an inhibitor of norepinephrine, dopamine and serotonina reuptake which inhibits food intake and increases thermogenesis. Sibutramine administration for a year can induce a weight loss of 4-7%. Its main side effects are hypertension, headache, insomnia and constipation. Orlistat is an inhibitor of pancreatic lipase which is able to block the absorption of 30% of ingested fat. Its administration induces weight loss and reduction of ulterior weight regain. Also, this drug improves hypertension dyslipdaemia and helps to prevent diabetes in 52% of cases when administered over four years. The increase in frequency of stools and interference with vitamin absorption are its main side effects. Glucagon-like peptide 1, which increases insulin sensitivity and satiety, adiponectin and PPAR-gamma agonists which reduce insulin resistance and modulates adipocyte generation are the basis for future therapeutic approaches of obesity. Phosphatase inhibitors induce PPAR-gamma phosphorylation and UCP-1 expression leading to an increase in thermogenesis and reduction in appetite.
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PMID:[Pharmacological treatment of obesity]. 1538 15

Autonomic dysreflexia is an autonomic behavioural condition that manifests after spinal cord injury (SCI) and is characterized by acute, episodic hypertension following afferent stimulation below the level of the injury. Common triggers of autonomic dysreflexia include colorectal distension (CRD), and various somatic stimuli. The development of autonomic dysreflexia is dependent, in part, upon the degree of intraspinal inflammation and the resultant spinal neuroplastic changes that occur following SCI. 17beta-estradiol (E) has neuroprotective, anti-inflammatory and smooth muscle relaxant properties, and is therefore a candidate drug for the treatment and/or prevention of autonomic dysreflexia. Autonomic dysreflexia was assessed in adult male mice treated with E. We investigated whether E could be acting centrally by altering: (1) the size of the small diameter primary afferent arbor, (2) the degree of microglia/macrophage infiltration at the site of the injury, or (3) the amount of fibrous scarring present at the injury site. To determine whether E could be working through uncoupling protein-2 (UCP-2), a protein involved with inflammation and regulated by estrogen in some tissues, autonomic dysreflexia was assessed in E-treated adult male mice lacking UCP-2 (UCP-2 KO). 17beta-estradiol was equipotent at reducing autonomic dysreflexia in both UCP-2 KO and WT mice following CRD but not tail pinch. We have shown that E reduces autonomic dysreflexic responses to visceral but not somatic stimulation in male mice independent of the size of the primary afferent arbour, the degree of chronic inflammation, and the presence of UCP-2.
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PMID:Estrogen reduces the severity of autonomic dysfunction in spinal cord-injured male mice. 1671 73

The aim of the present study was to clarify the effect of telmisartan, an angiotensin II receptor blocker, on the development of obesity and related metabolic disorders in diet-induced obese mice. Treatment with telmisartan dissolved in drinking water at a dosage of 5 mg/kg per day for 14 days attenuated the diet-induced weight gain without affecting food intake in diet-induced obese mice compared with controls using nontreated water. Telmisartan treatment decreased the weight of visceral adipose tissue and the triglyceride content in the liver and skeletal muscle. In addition, hyperglycemia, hyperinsulinemia, and hypertriglyceridemia in diet-induced obese mice all improved with telmisartan treatment. Furthermore, telmisartan treatment increased adiponectin mRNA in visceral white adipose tissue and was associated with a concomitant change in the serum adiponectin level. In contrast, the treatment reduced the serum level of resistin. Finally, telmisartan treatment increased the mRNA expression of uncoupling protein 1 in brown adipose tissue and was accompanied by an increase in oxygen consumption. In conclusion, telmisartan treatment might prevent the development of obesity and related metabolic disorders by altering the levels of adiponectin, resistin, and uncoupling protein 1 in diet-induced obese mice. Our results indicate that telmisartan can be used as a therapeutic tool for metabolic syndrome, including visceral obesity.
Hypertension 2006 Jul
PMID:Telmisartan prevents obesity and increases the expression of uncoupling protein 1 in diet-induced obese mice. 1671 45

Uncoupling protein 2 (UCP-2) is a newly identified member of the mitochondrial anion carrier family and shares 60% sequence identity with the well-characterized thermogenic UCP-1 from brown adipose tissue. Several lines of evidence suggest that UCP-2 is involved in the control of reactive oxygen species (ROS) production by mitochondria. More recently, a direct role for UCP-2 in the regulation of atherogenesis has been suggested by the observation that bone marrow transplantation from UCP-2-deficient mice to low-density lipoprotein receptor-deficient mice markedly increased atherosclerotic lesion size. This review introduces the possible role of UCP-2 in the regulation of atherogenesis in vascular cells. Although the relative contribution of the individual ROS generating systems in the vasculature is still ambiguous, both cell membrane NAD(P)H oxidase and the mitochondrial electron-transport chain have been proposed to play significant roles in the overproduction of ROS. UCP-2 can possibly modify atherosclerotic processes initiated in vascular cells and agents that increase UCP-2 expression in vascular cells may help prevent the development and progression of atherosclerosis in patients with diabetes or hypertension.
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PMID:The modulating effects of the overexpression of uncoupling protein 2 on the formation of reactive oxygen species in vascular cells. 1746 80

Atherosclerosis is a dynamic process. Dyslipidemia, diabetes mellitus, hypertension, obesity, and shear stress of blood flow, the risk factors for the development of atherosclerosis, are characterized by abnormalities in the metabolism of essential fatty acids (EFAs). Gene expression profiling studies revealed that at the sites of atheroslcerosis-prone regions, endothelial cells showed upregulation of pro-inflammatory genes as well as antioxidant genes, and endothelial cells themselves showed changes in cell shape and proliferation. Uncoupled respiration (UCP-1) precedes atherosclerosis at lesion-prone sites but not at the sites that are resistant to atherosclerosis. UCP-1 expression in aortic smooth muscle cells causes hypertension, enhanced superoxide anion production and decreased the availability of NO, suggesting that inefficient metabolism in blood vessels causes atherosclerosis without affecting cholesterol levels. Thus, mitochondrial dysfunction triggers atherosclerosis. Atherosclerosis-free aortae have abundant concentrations of the EFA-linoleate, whereas fatty streaks (an early stage of atherosclerosis) are deficient in EFAs. EFA deficiency promotes respiratory uncoupling and atherosclerosis. I propose that a defect in the activity of Delta6 and Delta5 desaturases decreases the formation of gamma-linolenic acid (GLA), dihomo-DGLA (DGLA), arachidonic acid (AA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) from dietary linoleic acid (LA) and alpha-linolenic acid (ALA). This, in turn, leads to inadequate formation of prostaglandin E1 (PGE1), prostacyclin (PGI2), PGI3, lipoxins (LXs), resolvins, neuroprotectin D1 (NPD1), NO, and nitrolipids that have anti-inflammatory and platelet anti-aggregatory actions, inhibit leukocyte activation and augment wound healing and resolve inflammation and thus, lead to the initiation and progression atheroslcerosis. In view of this, it is suggested that Delta6 and Delta5 desaturases could serve as biological target(s) for the discovery and development of pharmaceuticals to treat atherosclerosis.
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PMID:A defect in the activity of Delta6 and Delta5 desaturases may be a factor in the initiation and progression of atherosclerosis. 1746 97

Age-related disease, not aging per se, causes most morbidity in older humans. Here we report that skeletal muscle respiratory uncoupling due to UCP1 expression diminishes age-related disease in three mouse models. In a longevity study, median survival was increased in UCP mice (animals with skeletal muscle-specific UCP1 expression), and lymphoma was detected less frequently in UCP female mice. In apoE null mice, a vascular disease model, diet-induced atherosclerosis was decreased in UCP animals. In agouti yellow mice, a genetic obesity model, diabetes and hypertension were reversed by induction of UCP1 in skeletal muscle. Uncoupled mice had decreased adiposity, increased temperature and metabolic rate, elevated muscle SIRT and AMP kinase, and serum characterized by increased adiponectin and decreased IGF-1 and fibrinogen. Accelerating metabolism in skeletal muscle does not appear to impact aging but may delay age-related disease.
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PMID:Respiratory uncoupling in skeletal muscle delays death and diminishes age-related disease. 1805 18

Thiazolidinediones increase tissue insulin sensitivity and are protective against worsening of nephropathy and hypertension in diabetes. Mechanisms underlying protection at the renal level likely involve a variety of unknown changes in gene expression. We examined kidney gene expression in obese and lean Zucker rats in response to rosiglitazone (Avandia), a peroxisome proliferator activated receptor (gamma-subtype) agonist. Lean and obese Zucker rats were treated with either control chow or chow with added rosiglitazone (3 mg/kg x bw) for 12 weeks (n = 3/group). Total kidney mRNA expression was evaluated using the Affymetrix Rat Genome 230 2.0 GeneChip. 903 probe sets were significantly (P < 0.05) altered with at least 1.5-fold changes between groups. In untreated obese rats, 300 probe sets were increased and 244 decreased, relative to lean. Increased genes included the beta-subunit of the epithelial sodium channel (ENaC), the thiazide-sensitive Na-Cl cotransporter, and aquaporin 3. Decreased genes included angiotensin converting enzyme, type 1 (ACE1). FatiGO analysis showed that the highest number of altered genes between lean and obese belonged to the categories: ion binding, hydrolase activity, and protein binding. RGZ increased expression of uncoupling protein 1 (UCP1), CD36, and fatty acid binding protein 4 (FAbp4) in both lean and obese rats. In obese rats, 33 genes were normalized by RGZ (no longer different from lean) including ACE1, fatty acid synthase (Fasn), and stearoyl-coenzyme A desaturase (SCD1). Ingenuity Pathways System analysis of genes upregulated by RGZ in obese rats revealed two major nodes affected: PPAR-gamma and tumor necrosis factor alpha (TNF-alpha).
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PMID:Chronic rosiglitazone therapy normalizes expression of ACE1, SCD1 and other genes in the kidney of obese Zucker rats as determined by microarray analysis. 1870 Feb 76


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