Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Experiments were conducted to determine if food intake and adrenalectomy influenced abnormal antioxidant defense mechanisms observed in obese mice. Paired male C57BL/6J mice of two genotypes, obese (ob/ob) and lean (+/?), were fed a nonpurified diet ad libitum or restricted (2.5 g/d) until 3 mo old. Obese mice had larger livers and kidneys but smaller brains than lean mice. Plasma ceruloplasmin activity of obese mice was 240% of that of lean mice. Restricting food intake but not adrenalectomy reduced this difference, but ceruloplasmin activity of obese mice was still 150% of that of restricted-fed lean mice. Glutathione peroxidase (GSH-Px) activity in liver of obese mice was 70% of that in control lean mice; however, in kidney GSH-Px activity was 135% of that in obese mice. Both liver and kidney GSH-Px differences were eliminated by food restriction but not by adrenalectomy. Blood and brain GSH-Px activity was not influenced by the mutation. Liver and kidney copper-zinc superoxide dismutase activity was lower in obese mice than in lean littermates, 30 and 20%, respectively. Food restriction eliminated this difference in liver but not in kidney. Glutathione S-transferase activity using 1-chloro-2,4-dinitrobenzene as substrate was 55% lower in liver (not kidney) of obese mice than in lean mice and this difference was not markedly influenced by food restriction. Obese mice have marked changes in the steady-state activities of a number of protective enzymes that are organ dependent and, in part, due to the hyperphagia associated with this mutation.
 ...
PMID:Influence of genetic obesity, food intake and adrenalectomy in mice on selected trace element-dependent protective enzymes. 337 40

Nutritional obesity induced by the ingestion of hyperlipidic diet implies a high consume of lipids, which might be involved in oxygen metabolism. Double bound, in the fatty-acid molecules are a vulnerable point to undergo oxidation reactions-generating lipid peroxidation, that are potentially toxic and can produce serious cell injury (alteration in cell permeability and prostaglandins...). To prevent this oxidative injury the aerobic organisms have intracellular mechanisms of defense, the antioxidant systems, that may be classified as enzymatic and nonenzymatic. Vitamin C belongs to the second group and acts as scavenger of free radicals and other species. The purpose of this study was to evaluate the oxygen metabolism in isolated hepatocytes of rats which obesity has been reached by the ingestion of an hyperenergetic olive-oil rich controlled liquid diet and evaluate the effect of ascorbic acid. Cellular oxidative injury in isolated hepatocytes was induced through a lipid peroxidative and cytotoxic molecule tert-butyl-hydroperoxide (t-BOOH). Results show higher levels of lactate dehydrogenase (LDH) leakage and malondialdehyde (MDA) production in obese rats as compared with controls. Otherwise, when these groups are supplemented with ascorbic acid these changes decrease significantly. ATP levels decrease in hepatocytes of obese rats incubated in the presence of 1 mM tert-butylhydroperoxide. While it is maintained in ascorbic acid supplemented animals. GSH values were lower in hepatocytes from obese and control rats, incubated with tert-butyl-hydroperoxide. Supplementation with ascorbic acid also maintained GSH levels thus indicating that ascorbic acid is acting as an efficient antioxidant.
 ...
PMID:[Oxygen metabolism in isolated rat hepatocytes in obesity. Influence of vitamin C]. 941 88

Thanks to progress in zinc research, it is now possible to describe in more detail how zinc ions (Zn++) and nitrogen monoxide (NO), together with glutathione (GSH) and its oxidized form, GSSG, help to regulate immune responses to antigens. NO appears to be able to liberate Zn++ from metallothionein (MT), an intracellular storage molecule for metal ions such as zinc (Zn++) and copper (Cu++). Both Zn++ and Cu++ show a concentration-dependent inactivation of a protease essential for the proliferation of the AIDS virus HIV-1, while zinc can help prevent diabetes complications through its intracellular activation of the enzyme sorbitol dehydrogenase (SDH). A Zn++ deficiency can lead to a premature transition from efficient Th1-dependent cellular antiviral immune functions to Th2-dependent humoral immune functions. Deficiencies of Zn++, NO and/or GSH shift the Th1/Th2 balance towards Th2, as do deficiencies of any of the essential nutrients (ENs) - a group that includes methionine, cysteine, arginine, vitamins A, B, C and E, zinc and selenium (Se) - because these are necessary for the synthesis and maintenance of sufficient amounts of GSH, MT and NO. Via the Th1/Th2 balance, Zn++, NO, MT and GSH collectively determine the progress and outcome of many diseases. Disregulation of the Th1/Th2 balance is responsible for autoimmune disorders such as diabetes mellitus. Under Th2, levels of interleukin-4 (II-4), II-6, II-10, leukotriene B4 (LTB4) and prostaglandin E2 (PGE2) are raised, while levels of II-2, Zn++, NO and other substances are lowered. This makes things easier for viruses like HIV-1 which multiply in Th2 cells but rarely, if ever, in Th1 cells. AIDS viruses (HIVs) enter immune cells with the aid of the CD4 cell surface receptor in combination with a number of co-receptors which include CCR3, CCR5 and CXCR4. Remarkably, the cell surface receptor for LTB4 (BLTR) also seems to act as a co-receptor for CD4, which helps HIVs to infect immune cells. The Th2 cytokine II-4 increases the number of CXCR4 and BLTR co-receptors, as a result of which, under Th2, the HIV strains that infect immune cells are precisely those that are best able to accelerate the AIDS disease process. The II-4 released under Th2 therefore not only promotes the production of more HIVs and the rate at which they infect immune cells, it also stimulates selection for the more virulent strains. Zn++ inhibit LTB4 production and numbers of LTB4 receptors (BLTRs) in a concentration-dependent way. Zn++ help cells to keep their LTB4 'doors' shut against the more virulent strains of HIV. Moreover, a sufficiency of Zn++ and NO prevents a shift of the Th1/Th2 balance towards Th2 and thereby slows the proliferation of HIV, which it also does by inactivating the HIV protease. Research makes it look likely that deficiencies of ENs such as zinc promote the proliferation of Th2 cells at the expense of Th1 cells. Zinc deficiency also promotes cancer. Under the influence of Th1 cells, zinc inhibits the growth of tumours by activating the endogenous tumour-suppressor endostatin, which inhibits angiogenesis. The modern Western diet, with its excess of refined products such as sugar, alcohol and fats, often contains, per calorie, a deficiency of ENs such as zinc, selenium and vitamins A, B, C and E, which results in disturbed immune functions, a shifted Th1/Th2 balance, chronic (viral) infections, obesity, atherosclerosis, autoimmunity, allergies and cancer. In view of this, an optimization of dietary composition would seem to give the best chance of beating (viral) epidemics and common (chronic) diseases at a realistic price.
 ...
PMID:Modern diets and diseases: NO-zinc balance. Under Th1, zinc and nitrogen monoxide (NO) collectively protect against viruses, AIDS, autoimmunity, diabetes, allergies, asthma, infectious diseases, atherosclerosis and cancer. 1049 17

Free radicals have been suggested to play a role in the development of diabetic retinopathy. The aim of the present study was to examine whether the metabolic perturbations caused by high-fat feeding of two strains of mice, the C57BL6/J mice and the NMRI mice, interfere with one of the free radical enzyme defense systems in the retina, i. e., glutathione (GSH), and whether morphological changes occur in the retinal vessels. C57BL/6J mice and NMRI mice were fed a high-fat diet (55%) for 18 months. High-fat fed mice of both strains developed overweight, hyperinsulinemia, and hyperlipidemia. In addition, the high-fat fed C57BL/6J mice also developed sustained hyperglycemia for at least 15 months. The C57BL/6J mice had lower retinal GSH levels than the NMRI mice, both when given a normal diet (29.6+/-1.2 vs. 37.1+/-1.4 nmol/mg protein; p<0.01) and when given a high-fat diet (27.0+/-1.6 vs. 34.7+/-2.6 nmol/mg protein; p<0.05). Despite the long-standing hyperglycemia, hyperinsulinemia and hyperlipidemia in the C57BL/6J mice, high-fat feeding did not cause any changes in the retinal tissue levels of GSH (27.0+/-1.6 vs. 29. 6+/-1.2 nmol/mg protein) or cysteine (7.61+/-0.63 vs. 6.80+/-0.59 nmol/mg protein). Similarly, high-fat feeding did not affect retinal GSH or cysteine levels in NMRI mice. No light microscopical retinal vessel changes were seen, either in C57BL/6J or in NMRI mice. The study therefore shows that long-standing metabolic perturbations induced by dietary obesity do not induce signs of retinopathy in two different strains of mice. Further studies are needed to explore whether this is explained by increased expression of protecting systems making these strains of mice resistant to effects of oxidative stress.
 ...
PMID:Long-standing hyperglycemia in C57BL/6J mice does not affect retinal glutathione levels or endothelial/pericyte ratio in retinal capillaries. 1098 23

Environmental factors such as diet, physical activity, drugs, pollution and life style play an important role in the progression and/or precipitation of diseases like diabetes, hypertension, obesity and cardiovascular disorders. Indiscriminate use of antibiotics to combat infectious diseases is one of the commonest forms of misuse of drugs. Antibiotics seem to have a correlation with diabetes and pancreatic function. There are controversial reports about the effect of antibiotics on the pancreatic islets; some suggesting their harmless action, some depicting a beneficial role and others indicating deleterious effect. Moreover, use of antibiotics is mandatory during islet isolation and cultivation to reduce incidences of microbial contamination. It is likely that antibiotic treatment may adversely affect islet viability and its functioning leading to failure of islet transplantation. The present in vitro study was undertaken to examine the effect of commonly used antibiotics such as gentamycin, penicillin, streptomycin, tetracycline, neomycin, erythromycin and chloramphenicol on islet viability, its functioning and induction of oxidative stress if any. The viability and insulin production data showed that none of the antibiotics used in the present study affect the viability and the functioning of the islets at their pharmacological concentrations. Free radical levels measured in terms of melonyldialdehyde (MDA), nitric oxide (NO) and reduced glutathione (GSH) reveal that except for a marginal increase in lipid peroxidation with tetracycline and slight increase in NO levels with streptomycin, none of these antibiotics affect the oxidative status of the cells. Antioxidant enzymes such as superoxide dismutase and catalase remain unaffected after this treatment. Our results reveal the innocuous nature of the antibiotics used at pharmacological concentrations, suggesting their safety whenever prescribed to combat infections and also during islet isolation procedures.
 ...
PMID:Pancreatic islet-cell viability, functionality and oxidative status remain unaffected at pharmacological concentrations of commonly used antibiotics in vitro. 1156 80

Reactive oxygen species are produced in response to environmental toxins, and previous studies have suggested that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) damages a number of target organs through the generation of oxygen free radicals and oxidative stress. Upon exposure, TCDD becomes concentrated in adipose tissue, and adversely affects many organs, including liver. This study examined whether oxidative stress was induced in adipocytes and liver that were exposed to TCDD. 3T3-F442A adipocyte cultures were treated with TCDD (5-200 nM) for up to 72 h, and the activity and mRNA levels of superoxide dismutase (SOD), catalase, and glutathione peroxidase (GSH-Px) in adipocyte cell lysates were measured. The addition of 50 nM TCDD induced a two-fold increase in SOD activity after 48 h (P<0.05). In contrast, TCDD had no significant effect on the activity of catalase or GSH-Px in the adipocytes, and the increase in SOD activity was not accompanied by a change in SOD mRNA levels. To assess the effects of TCDD on oxidative stress enzymes in vivo, male Sprague-Dawley rats were injected weekly for 8 weeks with 30 ng/kg TCDD. In addition, the rats were fed either a low-fat complex-carbohydrate (LFCC) diet, or a high fat sucrose diet (HFS). The HFS diet has previously been shown to induce mild obesity and insulin resistance, without inducing diabetes. SOD, catalase, and GSH-Px activities were measured in the liver and adipose tissue of these rats. TCDD injection resulted in a 52% decrease in catalase activity in the adipose tissue of HFS rats (P<0.05). In contrast, SOD and GSH-Px activities were not altered in adipose tissue of TCDD-injected rats. In liver, however, there were significant decreases in GSH-Px activity in response to TCDD. This effect of TCDD was observed in both the LFCC and HFS dietary groups. In addition, GSH-Px activity in the HFS rats was significantly decreased when compared to GSH-Px activity in LFCC rats, in both TCDD-treated and control groups, suggesting that TCDD and a high fat diet may combine to exacerbate oxidative stress. Thus, TCDD induces complex changes in enzymes of oxidative stress in both adipocytes and liver. In adipocytes, these changes occurred post-transcriptionally, as there were no changes in mRNA levels. In addition, a high fat diet per se also resulted in a decrease in GSH-Px activity in liver.
 ...
PMID:The effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on oxidative enzymes in adipocytes and liver. 1183 18

Obesity is commonly associated with a high incidence and prevalence of dyslipidaemia, cardiovascular disease and Type II diabetes. Interestingly, studies have also reported decreased antioxidant levels in obese subjects. This may constitute an independent risk factor in the pathogenesis of coronary artery disease as obese subjects would have a decreased capacity to prevent the oxidative modification of low-density lipoproteins, which is a mechanism suggested as central to the development of atherogenesis. As part of a study to investigate responses to weight loss, we have assessed the effects on GSH status of a decrease in body mass of 5%, either after 6 days of complete starvation or 11 days of a very low calorie diet (2.55 MJ/day). There were significant differences between the two groups in the synthesis rate of erythrocyte GSH in response to weight loss. Both the fractional and the erythrocyte synthesis rate of GSH decreased significantly (P<0.01) in the starvation group by 22% and 16% respectively. In contrast, no change in synthesis rates was observed in the very low calorie diet group (P>0.05). Total erythrocyte concentration of GSH was unaffected by the weight loss within both groups. These results suggest that erythrocyte GSH synthesis is depressed in response to a very rapid weight loss induced by fasting. An acute reduction in GSH synthesis in response to a rapid weight loss may constitute a risk factor during periods of increased GSH demands.
 ...
PMID:The effect of rate of weight loss on erythrocyte glutathione concentration and synthesis in healthy obese men. 1198 May 77

Reduced tolerance of steatotic livers to ischemic injury is considered to correlate with impaired microcirculation. The aim of this study was to investigate the impact of heat-shock preconditioning (HSPC) on microcirculatory failure after ischemia/reperfusion (I/R) in steatotic livers by means of intra-vital fluorescence microscopy. Obese Zucker rats were used. In the HS group, rats underwent whole-body hyperthermia followed by 60-min partial liver ischemia. In group IR, rats were exposed only to ischemia. Microcirculation parameters (sinusoidal perfusion rate, sinusoidal diameter, leukocyte-endothelial interaction) were significantly better preserved in the HS group than in the IR group. Liver enzymes, oxygenated glutathione/reduced glutathione (GSSG/GSH) ratio, and electron microscopy showed less damage in the HS group. A marked expression of heat shock protein 72 (HSP72) and heme oxygenase (HO-1) was found only in the livers of group HS. HSPC mitigated the I/R injury of steatotic livers by preventing post-ischemic failure of microcirculation. This beneficial effect was found to be associated with the induction of HSP72 and HO-1.
 ...
PMID:Heat-shock preconditioning protects fatty livers in genetically obese Zucker rats from microvascular perfusion failure after ischemia reperfusion. 1269 40

A positive family history of coronary heart disease (CHD) is one of the most predictive risk factors of CHD. Many children with increased risk of CHD because of their positive family history of CHD do not present other risk factors, such as altered serum lipid profile. Oxidative stress plays an important part in the pathogenesis of atherosclerosis. Serum antioxidants and intracellular enzymatic antioxidants composed mainly of glutathione peroxidase (GSH-Px), catalase (CAT), superoxide dismutase (SOD) and glutathione reductase counterbalance oxidative stress. Diminished activity of this system may lead to accelerated progression of atherosclerosis. The aim of this study was to assess the activity of CAT, GSH-Px, SOD and glutathione reductase in children with a family history of premature CHD who did not present any other major risk factors of CHD (diabetes, obesity, dyslipidaemia or hypertension). Twenty-two healthy children from high-risk families, selected according to the National Cholesterol Education Program definition, were enrolled in the study. The control group comprised 18 children without a family history of CHD. All the children were healthy and had been screened for hyperlipidaemia, diabetes, hypertension and obesity prior to the study. The erythrocyte activity of CAT, GSH-Px, SOD and glutathione reductase was assessed. Children at high risk of CHD had a statistically significant lower level of GSH-Px and CAT activity than the children in the control group. There were no statistically significant differences in the activity of SOD and glutathione reductase.
 ...
PMID:Activity of antioxidant enzymes in children from families at high risk of premature coronary heart disease. 1275 97

Obesity is accompanied by a high incidence of atherosclerosis, arterial hypertension and non-insulin dependent diabetes mellitus in the pathogenesis of which is associated with oxygen-derived free radicals. The aim of the study was to compare blood oxidation status in obese women without coexisting diseases and in healthy women with normal body mass index (BMI). Studies were performed in 29 premenopausal obese (BMI 35.79 +/- 4.62 kg/m2) and 31 lean (BMI 22.29 +/- 1.05 kg/m2) women. Plasma lipid profile, activities of antioxidant enzymes: copper/zinc (Cu/ZnSOD) and manganese-containing superoxide dismutase (MnSOD) and glutathione peroxidase (GSH-Px), as well as concentrations of malondialdehyde (MDA)--a product of lipid peroxidation, were examined. In obese women there were significantly higher concentrations of total cholesterol (5.02 +/- 0.83 vs. 4.15 +/- 0.43 mmol/l; p < 0.05), LDL-cholesterol (3.12 +/- 0.90 vs. 2.35 +/- 0.42 mmol/l; p < 0.05) and triglycerides (1.72 +/- 0.85 vs. 1.02 +/- 0.18 mmol/l; p < 0.01), while HDL-cholesterol level was lower (1.01 +/- 0.16 vs. 1.25 +/- 0.2 mmol/l; p < 0.05). Moreover, in comparison to the control group, obese women showed increased activities of plasma MnSOD (6.72 +/- 1.43 vs. 4.99 +/- 0.58 NU/ml; p < 0.05) and erythrocyte GSH-Px (35.38 +/- 10.31 vs. 19.15 +/- 7.12 mumol NADPH2/g Hb/min; p < 0.001), and concentrations of plasma MDA (2.93 +/- 0.53 vs. 2.16 +/- 0.31 mumol/l; p < 0.05) and erythrocyte MDA (2.24 +/- 0.30 vs. 1.59 +/- 0.36 mumol/g Hb; p < < 0.001). There were no differences between the two groups in activities of plasma and erythrocyte Cu/ZnSOD. In conclusion, the results demonstrate disturbances in oxidation status in premenopausal obese women with abnormal lipid profile, which may indicate the association between oxygen-derived free radicals and the increase in the incidence of obesity-related diseases.
 ...
PMID:[Assessment of blood superoxide dismutase, glutathione peroxidase activity and malondialdehyde concentration as oxidation status parameters in obese women]. 1468 7


1 2 3 4 5 6 7 8 9 10 Next >>