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

The obese ZDFxSHHF-fa/fa(cp) model was developed by crossing lean female Zucker Diabetic Fatty (ZDF +/fa) and lean male Spontaneously Hypertensive Heart Failure (SHHF/Mcc-fa(cp), +/fa) rats. The purpose of the present study was to determine renal function and morphology, hemodynamics, and metabolic status in ZDFxSHHF rats. Two sets of experiments were conducted. First, we evaluated heart and kidney function and metabolic status in aged (46 weeks old) male obese ZDFxSHHF and age matched obese SHHF rats, lean Spontaneously Hypertensive (SHR) and lean normotensive Wistar Kyoto (WKY) rats. In the second set of experiments, renal function and structure as well as metabolic and lipid status were determined in lean (LN) and obese (OB) adult (29-weeks of age) ZDFxSHHF rats. At 46 weeks of age ZDFxSHHF rats are hypertensive expressing marked cardiac hypertrophy associated with diastolic dysfunction and preserved contractile function. Fasted hyperglycemia and hyperinsulinemia are accompanied by moderate hypercholesterolemia and hypertriglyceridemia. Obese aged ZDFxSHHF have marked renal hypertrophy, a 3-8 fold decrease in creatinine clearance (compared with SHHF, SHR and WKY), a high percent of segmental + global glomerulosclerosis (59.8%+/-10.8), and severe tubulointerstitial and vascular changes. Obese ZDFxSHHF rats die at an early age (approximately 12 months) from end-stage renal failure. Studies conducted in 29-week animals showed that, although both LN and OB 29-week old animals are hypertensive, OB animals have more severely compromised renal function and structure as compared with lean litter-mates (kidney weight: 2.56+/-0.16 vs. 1.61+/-0.12 g; creatinine clearance: 0.42+/-0.04 vs. 1.24+/-0.13 L/g kid/day; renal vascular resistance 12.39+/-1.4 vs. 6.14+/-0.42 mmHg/mL/min/g kid; protein excretion: 556+/-16 vs. 159+/-9mg/day/g kid, p < 0.05, OB vs. LN, respectively). Obesity is also associated with hyperglycemia (424+/-37 vs. 115+/-11 mg/dL), hyperinsulinemia (117.2+/-8.8 vs. 42.3+/-3.5 microU/mL), hypertriglyceridemia (5200+/-702 vs. 194+/-23 mg/dL), hypercholesterolemia (632+/-39 vs. 109+/-4mg/dL), and presence of segmental + global glomerulosclerosis (20.1+/-3.2% vs. 0.1+/-0.1%) with prominent tubular and interstitial changes (p < 0.05, OB vs. LN, respectively). In summary, the present study indicates that the crossing of rat strains of nephropathy produces hybrids that carry a high risk for severe renal dysfunction. The ZDFxSHHF rats express insulin resistance, hypertension, dislipidemia and obesity and develop severe renal dysfunction. In addition, the hybrids do not develop some of the complications (hydronephrosis or congestive heart failure) common for the parental strains that may compromise studies of renal function and structure. Therefore, the ZDFxSHHF rat may be a useful model fore valuating risk factors and pharmacological interventions in chronic renal failure.
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PMID:Renal function and structure in diabetic, hypertensive, obese ZDFxSHHF-hybrid rats. 1090 Nov 78

It has previously been demonstrated that oCRF and the CRF binding protein inhibitor CRF (6-33) reduce body-weight gain in obese Zucker rats. We investigated whether the reduction in body-weight is attributable to altered feeding and drinking behaviour. Obese Zucker rats were fitted with osmotic mini-pumps connected to i.c.v. cannulas. Vehicle, oCRF (5 microg/day) or CRF (6-33) (25 microg/day) were infused for 7 days and the animals observed for an additional 7 days. Body-weight and food and water-intake were recorded daily at 14.00 h. In agreement with published results, oCRF and CRF (6-33) significantly reduced body-weight gain in the obese Zucker rat. In addition, food intake was reduced, whereas water consumption was unaffected.
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PMID:oCRF and CRF (6-33) depress food but not water intake in the obese Zucker rat. 1099 35

While the ethnic make up of the New Zealand population is predominantly European, the Polynesian population, consisting of indigenous New Zealand Maori and more recent immigrants from the other Pacific Islands is increasing rapidly. The prevalence of diabetes in these Polynesians is high. There is also an increasing prevalence of obesity, and obesity is a greater problem amongst Polynesian people. The number of elderly people in the population is increasing. All of these demographic changes are increasing the incidence and prevalence of Type 2 diabetes. The incidence of Type 1 diabetes is also rising, although the reasons for this are unknown. Diabetic nephropathy is the most common cause of end stage renal failure in New Zealand. Polynesian people with diabetes, and in particular Maori, have a very high rate of diabetic nephropathy and develop renal failure at a more rapid rate than European patients with nephropathy relating to Type 1 diabetes. The propensity for Maori patients with Type 2 diabetes to develop renal failure may relate to a younger age at the onset of diabetes, a genetic susceptibility to nephropathy, and socio-economic or cultural factors leading to less adequate medical care.
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PMID:Diabetes in New Zealand. 1102 86

Experimental evidence suggests a role for obesity in the formation and progression of some glomerular lesions, but data for human glomerulonephritis are lacking. In a cohort of 162 incident patients with biopsy-proven immunoglobulin A (IgA) nephropathy, we assessed whether the presence of an elevated body mass index (BMI >/= 25 kg/m(2)) at the time of the first renal biopsy (RB1) correlated with clinical data at RB1 (24-hour proteinuria, arterial hypertension, and renal function), pathological data (global optical score [GOS] with detailed pathological indices), and clinical progression to both arterial hypertension and chronic renal failure (CRF). In both univariate and multivariate analyses, the presence of an elevated BMI at RB1 was significantly associated with the severity of pathological renal lesions (GOS and vascular, tubular, and interstitial indices). Hypertension-free survival was significantly less in overweight patients (P: < 0.0001) compared with those with normal weight. In a Cox regression analysis for hypertension-free survival including 24-hour proteinuria greater than 1 g, GOS, and metabolic parameters, only elevated BMI and GOS were independent factors for the development of arterial hypertension. CRF-free survival was also significantly less in patients with an excessive BMI. In a multivariate Cox regression analysis for CRF-free survival, hypertension, GOS, and BMI at RB1 were independent risk factors for CRF. In IgA nephropathy, excessive body weight and/or BMI are underestimated predictive factors for the development of arterial hypertension and, ultimately, CRF.
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PMID:Excessive body weight as a new independent risk factor for clinical and pathological progression in primary IgA nephritis. 1127 71

A pandemic of obesity is contributing importantly to the prevalence of the metabolic syndrome characterized by hypertension, insulin resistance, and hyperlipidemia. In turn, the metabolic syndrome is contributing to vascular disease and the accelerating epidemic of chronic renal failure. Currently, pharmacological approaches to attenuate obesity and its cardiovascular/renal sequelae are limited. The purpose of this study was to determine the effects of 2-hydroxyestradiol, a metabolite of 17beta-estradiol with minimal estrogenic activity, on the development of obesity, the metabolic syndrome, and heart, vascular, and renal dysfunction in obese ZSF1 rats, a well-characterized genetic model of obesity and the metabolic syndrome with concomitant heart, vascular, and kidney disease. ZSF1 rats were treated, beginning at 12 weeks of age, for 26 weeks with vehicle or 2-hydroxyestradiol (10 microg/kg/h). At baseline and after 24 weeks of treatment, animals were placed in metabolic cages, and food intake, water intake, urine output, and urinary excretion of proteins and glucose were determined. Next, in fasting animals, plasma cholesterol was measured, an oral glucose tolerance test was conducted, and total glycated hemoglobin levels were determined. At the end of the study, animals were anesthetized and instrumented for assessment of heart performance, renal hemodynamics, and mesenteric vascular reactivity. 2-Hydroxyestradiol attenuated the development of obesity and improved endothelial function, decreased nephropathy, decreased the severity of diabetes, lowered arterial blood pressure, and reduced plasma cholesterol. 2-Hydroxyestradiol may be an important lead for the development of safe and effect drugs to attenuate obesity and its metabolic, vascular, and renal sequelae.
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PMID:2-Hydroxyestradiol attenuates the development of obesity, the metabolic syndrome, and vascular and renal dysfunction in obese ZSF1 rats. 1171 85

Given the current global epidemic of obesity there is a demand for new anti-obesity drugs to overcome the problem. Many pharmacological agents reduce food intake and significantly decrease body mass when administered to animals but affect feeding behaviour in a profoundly different way indicating the variety of biological mechanisms by which such agents act (appetite verses non-appetite). More limited clinical data demonstrates that some of the same drugs produce decreases in food intake and weight loss in humans. A few of these drugs do so by modifying the functioning of the appetite system as measured by subjective changes in feelings of hunger and fullness (indices of satiety). These drugs that modify the daily flux of appetite could be considered as 'appetite suppressants' with clinical potential as anti-obesity agents. Drugs that can be considered suitable candidates for appetite suppressants are agents that enhance peripherally satiety peptide systems (such as CCK, Bombesin/GRP, Enterostatin and GLP-1), alter the CNS levels of various hypothalamic neuropeptides (NPY, Galanin, Orexin, CART and Melanocortins) or monoamine neurotransmitters (such as serotonin, nor-adrenaline and possibly dopamine). Recently, the hormone leptin has become regarded as a key hormonal signal linking adipose tissue status with a number of key central nervous system circuits (NPY, CART, CRF, Melanocortins and possibly Orexins). This tonic system may also provide drug targets for the control of appetite. Any changes induced by a potential appetite suppressant should be considered in terms of the (i) psychological experience and behavioural expression of appetite, (ii) metabolism and peripheral physiology, and (iii) functioning of CNS neural pathways. In humans, such modulation of appetite will involve changes in total caloric consumption, subjective changes in feelings of hunger and fullness, preferences for specific food items, and general macronutrient preferences. These may be expressed behaviourally as changes in meal patterns, snacking behaviour and food choice. Within the next 20 years it is certain that clinicians will have a new range of anti-obesity compounds available to choose from. Such novel compounds may act on a single component of the appetite system or target a combination of these components detailed in this review. Such compounds used in combination with life style changes and dietary intervention may be critical in dealing with the rising world epidemic of obesity.
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PMID:Pharmacology of appetite suppression: implication for the treatment of obesity. 1173 37

A recent review of our center experience revealed that only 38% of our pediatric renal transplants come from living-related donors (LRD), which is 11% lower than the national average. The present study was designed to identify factors that limit the availability of LRD in our population pool. Retrospective chart reviews and subsequent telephone interviews were conducted with parents of all children who received renal replacement therapy (RRT) at our institution from 1990 to 1999. The availability of parents and their willingness to donate a kidney were noted. Self-reported willingness was defined as the verbal expression of a desire to donate. Firm willingness was defined as the completion of the steps necessary for donation, unless excluded by the medical team. Factors that may impact the ability to donate, such as donor age, ethnicity, religion, educational attainment, employment, and presence of other siblings younger than 18 yr of age, were evaluated. Statistical analyses were performed using the Student's t-test and chi-square analysis. Significant results were entered into a single-step multiple regression analysis. Sixty children were identified with RRT, of whom 60% were Blacks, 30% Hispanics, 7% Caucasians, and 3% Asian. Fifty-five mothers were available for interview. Forty-four mothers reported a desire to donate, nine were unwilling to donate, and two were undecided. However, only 35 attended for screening. Only 30 fathers were available and, of these, 27 reported willingness to donate, yet only 20 attended for screening. Seventy-four per cent (26 out of 35) of mothers screened and 55% (11 out of 20) of fathers screened were medically unsuitable for kidney donation. Nineteen potential donors had hypertension, diabetes and/or obesity, seven had renal disease, four had anemia, two had hepatitis C, and five had other conditions. Expressed unwillingness to donate was associated with a greater number of children (3.1 compared to 1.5 children in addition to the child with end-stage renal disease [ESRD]) (odds ratio 2.91, p < 0.05) and employment (26.3% vs. 4.0%, p < 0.05) (odds ratio 31.2, p = 0.05). Comparing mothers who were firmly willing to donate with mothers who did not complete screening and evaluation, unwilling mothers had, likewise, a greater number of children (2.9 vs. 1.2 in addition to the child with ESRD) (odds ratio 3.23, p < 0.01) and a greater number of years of education (12.4 vs. 10.4) (odds ratio 2.14, p < 0.05). Hence, the availability of living kidney donors for our inner city children is severely limited by a high rate of single parenthood and a high rate of comorbid conditions in the parental donor pool. Furthermore, there is a diminished capacity of the available parent, particularly the mother, to donate as she tends to have numerous other dependents.
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PMID:Factors limiting the rate of living-related kidney donation to children in an inner city setting. 1173 66

Patients with end stage renal disease have a high prevalence of cardiovascular disease and coronary arteriography is often routinely performed prior to kidney transplantation. However, the value of the conventional risk factors and non-invasive markers of coronary artery disease (CAD) in triaging patients for coronary arteriography has not been fully examined. 116 patients with end stage renal disease were evaluated. Coronary arteriography was performed in all patients either for a suspicion of CAD or as part of a routine pre-transplant evaluation. Lesions causing > or = 50% luminal diameter stenosis in any of the three major coronary artery systems were considered significant. The mean age was 53.3 +/- 9.3 years. Significant CAD was present in 69 patients (60%). Increasing age, family history of premature ischemic heart disease, the presence of angina, abnormal Q waves on the ECG or abnormal ST segment depression and the presence of coronary calcification were significant markers of coronary artery disease. However male gender, diabetes mellitus and obesity did not correlate with coronary disease. Even though hypertension, hypercholesterolemia and smoking were also not useful predictors these could have been modified by the renal failure. In conclusion increasing age, a family history of premature ischemic heart disease and some non-invasive markers were useful predictors of coronary disease.
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PMID:Predictors of coronary disease in patients with end stage renal disease. 1177 19

Chronic renal failure and ESRD are major causes of morbidity, mortality, and chronic disability in patients in the United States. Hypertension is a major underlying cause of chronic progressive renal disease and continues to be a leading reason for the heavy burden of ESRD observed in African Americans. Hypertension is actually a syndrome of vascular pathology manifesting itself in patients by a constellation of common findings and attributes. These pathophysiologic alterations include dysregulation of arterial compliance, endothelial dysfunction, obesity and insulin resistance, abnormal sympathetic nervous system activation, accelerated atherosclerosis, left ventricular hypertrophy, and a propensity for increased vascular thrombogenesis among others. This review will focus on some of the important mechanisms possibly involved in the progression of renal disease in the setting of chronic hypertension.
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PMID:Pathophysiology of chronic progressive renal disease in the African American patient with hypertension. 1186 82

Malnutrition is very frequent comorbid factor in chronic renal failure and its prevalence both in the predialysis period as well as on maintenance dialysis is high. The aim of the study was to assess the nutritional status in patients after successful kidney transplantation. 109 patients (47 F, 67 M) of mean age 39.9 +/- 11.5 years were analyzed. Mean time after transplantation surgery was 32.2 +/- 37 months and the maintenance dialysis treatment period prior to transplantation--28.4 +/- 22 months. Nutritional status was assessed with clinical examination based on the SGA scale, anthropometric measurements as well as body composition estimation with bioimpedance. Daily food intake was also monitored with three-day dietary questionnaire. All above analyses were also performed in 25 healthy control subjects with corresponding sex and age distribution. No differences between all analyzed bioimpedance and anthropometry parameters were found between studied patients and controls. 79% of patients were classified as well nourished, 20%--as mildly or moderately malnourished and only 1%--as severely malnourished according to SGA scale. The BMI values less than 21 kg/m2, i.e. suggesting malnutrition were found in 23.3% of patients, whereas values above 25 kg/m2, i.e. suggesting overweight or obesity--in almost 40%. Interestingly, as high as 82.5% of studied patients were characterized by significant weight gain since last "dry weight" assessment on maintenance dialysis up to the time of study (by mean 9.42 +/- 6.9 kg). Obtained results permit us to conclude, that the prevalence of nutritional status abnormalities are relatively frequent among patients with functioning graft. Malnutrition can be demonstrated in more than 20% of the study population, which should be considered however to be markedly lower as compared to most reports regarding dialysis populations. Weight gain during posttransplant period as compared to maintenance dialysis is marked and common; thus the prevalence of obesity is also quite common and reaches 40% of tested patients.
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PMID:[Nutritional status of patients with functioning graft assessed by clinical examination, anthropometry and bioimpedance]. 1186 40


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