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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In animals with reduced renal mass increased glomerular filtration is associated with accelerated glomerular sclerosis. Whether hyperfiltration causes glomerular damage in humans is unknown. Since increased glomerular filtration occurs in obesity, the amount of glomerular sclerosis found in renal autopsy tissue from 46 patients with massive obesity was compared to that found in 46 normal body weight controls. Despite increased kidney weight and glomerular size, obese patients had the same proportion of completely sclerosed glomeruli as controls. In addition, no focal segmental glomerular sclerosis was seen in the obese group. It is concluded that patients with massive obesity have increased kidney weight and nephron size consistent with hyperfiltration. Nevertheless, massively obese patients do not appear to have increased glomerular sclerosis.
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PMID:Glomerular sclerosis in patients with massive obesity. 397 78

Although hyperphagia and obesity in the Zucker rat strain have been reported to be associated with spontaneous focal glomerulosclerosis (FGS), little is known about the age of onset and the natural history of hypertension, albuminuria, renal function, and glomerular injury in this model. We systematically investigated renal structure and function in obese male Zucker rats. Lean male littermates were used as controls. Obese rats developed glomerular mesangial matrix expansion and albuminuria by 14 weeks of age. These changes occurred despite normal inulin clearance (2.2 +/- 0.6 ml/min obese vs. 2.0 +/- 0.4 ml/min lean, P greater than 0.1) and filtration fraction (0.32 +/- 0.08 obese vs. 0.34 +/- 0.06 lean, P greater than 0.1), suggesting that increased glomerular filtration and renal plasma flow were not a prerequisite for the development of FGS. By 28 weeks of age, FGS was evident in seven of eight obese rats, and at 68 weeks of age all obese rats had marked FGS. Mean systolic blood pressure was elevated by 11 to 25 mm Hg in obese rats at all ages. Although the pathogenesis of glomerular injury is unknown, our data demonstrate that microalbuminuria, mild hypertension, and mesangial matrix expansion precede the development of progressive FGS in obese Zucker rats.
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PMID:Effects of genetic obesity on renal structure and function in the Zucker rat. 405 70

Advances in our understanding of the mechanisms of proteinuria in humans have depended on a variety of animal models. Most of these have been partially satisfactory because they require pretreatment of the animal with chemicals or toxins or they depend on an aging-related glomerular protein leakiness. The strain in this study was obtained by Koletsky after selective inbreeding of the offspring from a hypertensive Kyoto-Wistar and a normotensive Sprague-Dawley rat. The affected animals appear in 25% of the litters, indicating an autosomal recessive gene, and present with a spontaneous and progressive nephrotic syndrome detected as early as 3-5 weeks and associated with obesity, hypertension, hypoalbuminemia, hypercholesterolemia, and hyperlipidemia. Preliminary morphologic and immunofluorescence studies of their kidneys show progressive glomerular segmental sclerotic lesions and prominent mesangial deposition of IgM, a picture which resembles a steroid-resistant form of idiopathic nephrotic syndrome in humans, namely, focal glomerular sclerosis.
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PMID:Spontaneous nephrotic syndrome in a genetic rat model. 650 87

The New Zealand Obese (NZO) mouse was studied as a potential model for autoimmune diabetes. NZO mice develop obesity, glucose intolerance, and insulin resistance, and have low-titer IgM antibodies to the insulin receptor. It is shown that they have circulating antibodies to both native DNA and denatured, single-stranded DNA. The antibody levels are higher in females, and, up to 6 mo of age, are comparable to those found in the related NZB X NZW F1 (NZB/W) mouse, a model for systemic lupus erythematosus. After 6 mo of age the antibody levels in NZO mice fall toward normal, in contrast to the persistently elevated levels in NZB/W mice. NZB/W mice are known to succumb to immune complex-mediated proliferative glomerulonephritis before 1 yr of age, whereas NZO mice survive. NZO kidneys exhibit light microscopic features of both diabetic and lupus nephropathies: glomerular proliferation, mesangial deposits, mild basement membrane thickening, glomerulosclerosis, eosinophilic nodules in some glomeruli, occasional hyalinization of the glomerular arterioles, and healing arteriolar inflammation. These changes are associated with glomerular deposition of immunoglobulin, especially IgM, in a granular pattern on fluorescent staining. The NZO mouse, therefore, has evidence of a generalized immune disorder and provides a model for studying the relationship between autoimmunity, obesity, and diabetes.
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PMID:Diabetes is associated with autoimmunity in the New Zealand obese (NZO) mouse. 700 65

Genetically obese and hypertensive rats (Obese/SHR) were subjected to sham or bilateral adrenalectomy at 4-5 weeks of age with the onset of hyperphagia. The sham-operated Obese/SHR ate voraciously and by 180 days of age males weighed 700 g and females 590 g. The adrenalectomized Obese/SHR ate much less and weighed 325 and 225 g. The systolic blood pressure of the intact Obese/SHR ranged from 160 to 170 mmHg, whereas the blood pressure of the adrenalectomized animals ranged from 108 to 110 mmHg. The thymi of the intact Obese/SHR were massive compared to those of the adrenalectomized rats. Adrenalectomy effectively reduced the hyperinsulinaemia, adiposity, hyperlipidaemia, hyperglycaemia, and elevated BUN levels of the obese rats. Several obese rats had old or new myocardial infarcts, fatty livers, giant-sized islets of Langerhans, nodular and hyperaemic adrenal glands, narrow zona glomerulosa devoid of lipid, vacuolated inner cortical zones, foci of intimal fibrinohyalin deposits in mesenteric arteries, early glomerulosclerosis, and large, rounded bladder calculi. The adrenalectomized Obese/SHR displayed none of these stigmata. It is suggested that the genetically programmed obesity and hypertension in these SHR are mediated by abnormal activity of the hypothalamic-pituitary-adrenal-gonadal axis, may be likened to Cushing's disease in the human, and is associated with accelerated ageing.
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PMID:Ameliorative effects of adrenalectomy on the hyperphagia, hyperlipidaemia, hyperglycaemia and hypertension of obese, spontaneously hypertensive rats (Obese/SHR). 701 60

The conversion of xanthine dehydrogenase to xanthine oxidase that produces oxygen radicals has been implicated in the ischemic injury to the myocardium and to the kidney. Xanthine dehydrogenase uses NAD as the electron acceptor to catalyze a reaction which does not produce any oxygen free radicals and may depress the conversion of xanthine dehydrogenase to xanthine oxidase. Nicotinamide is the preferred precursor for NAD. This study was conducted to examine the effect of an 18% casein diet supplemented with 0.5% nicotinamide on the activity of oxidoreductase and its two enzyme forms, xanthine dehydrogenase and xanthine oxidase, in kidney, heart and liver of female obese Zucker rats that spontaneously develop glomerulosclerosis, cardiomegaly and fatty liver. Lean litter mates were used as controls. Nicotinamide supplementation had no effect on the activities of these enzyme forms in the liver of either obese rats or lean rats. Obese rats fed the nicotinamide supplemented diet had higher activities of these enzyme forms in kidneys and hearts than unsupplemented diet fed obese rats, but this difference was not observed in lean rats. In unsupplemented rats, xanthine oxidase activity in the kidney was greater in lean rats than obese rats. Thus, the abnormalities observed in obese rats are unlikely attributable to the xanthine oxidase-mediated oxidant stress.
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PMID:Dietary nicotinamide supplementation increases xanthine oxidoreductase activity in the kidney and heart but not liver of obese Zucker rats. 761 99

We have identified 17 obese patients (body mass index, BMI, 37.9 +/- 4.1) with proteinuria > 1 g/day (1.3-6.4 g/24 h, mean 3.1 +/- 1.7). Their age was 34-70 years (48.3 +/- 10); 11 were females and 6 males. Six patients had only one functioning kidney and a sleep apnea syndrome had been diagnosed in 5. Renal biopsies, obtained in 5 cases, showed focal glomerulosclerosis in 2 cases, minimal changes in 2 and mesangial proliferation in 1. Nine patients (group 1) were treated with hypocaloric diets; body weight significantly decreased (BMI 37.1 +/- 3, 34 +/- 3.5 and 32.6 +/- 3.2 at 0, 6 and 12 months, respectively) as well as proteinuria (2.9 +/- 1.7, 1.2 +/- 1 and 0.4 +/- 0.6 g/24 h). There was a significant correlation between body weight loss and decrease in proteinuria (r = 0.69, p < 0.05). Eight patients (group 2) were treated with captopril, without dietary changes. BMI remained stable but proteinuria showed a dramatic decrease, similar to that in group 1 (3.4 +/- 1.7, 1.2 +/- 0.9 and 0.7 +/- 1 g/24 h, respectively). Renal function remained stable in both groups. In summary, both body weight loss and captopril treatment can induce a sharp decrease in obesity-related proteinuria.
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PMID:Effects of body-weight loss and captopril treatment on proteinuria associated with obesity. 761 15

The characteristic features of OLETF rats are: (1) late onset of hyperglycemia (after 18 weeks of age); (2) a chronic course of disease; (3) mild obesity; (4) clinical onset of diabetes mellitus (DM) mostly in males; (5) hereditary trait: (a) multiple recessive genes are involved in the induction of DM; (b) rat MHC, RT1 has no diabetogenic effect; (c) control strain, LETO appears to share some of diabetogenic genes with OLETF rats; (d) female OLETF rats also carry diabetogenic genes; and (e) one of the diabetogenic genes, designated as odb-1, is transmitted linked with the X-chromosome of OLETF rats, however testosterone is an important factor involved in developing diabetes; (6) the changes of pancreatic islets can be classified into three stages: (1) an early stage (at less than 9 weeks of age) mild lymphocyte infiltration; (2) a hyperplastic stage (10-40 weeks of age); hyperplastic change and fibrosis in or around islets; (3) a final stage (at more than 40 weeks of age) showing atrophy of islets; (7) diabetic nephropathy; (a) diffuse glomerulosclerosis; (b) nodular lesion (thickening of basement membranes, mesangial proliferation, fibrin cap). These clinical and pathologic features of disease in OLETF rats resemble those of human NIDDM.
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PMID:OLETF (Otsuka Long-Evans Tokushima Fatty) rat: a new NIDDM rat strain. 785 27

Obese Zucker rats spontaneously develop lipoprotein abnormalities, proteinuria, mesangial expansion and glomerulosclerosis. Previous studies have implicated these lipoprotein abnormalities in the pathogenesis of the progressive renal injury which these rats develop. The present study was designed to examine the chronological development of very-low-density lipoprotein (VLDL) abnormalities and renal injury. Obese and lean Zucker rats were maintained on a standard rat diet and sacrificed at 6, 11, 17, 23, 28, and 34 weeks of age. Renal tissue was examined histologically, serum was assayed for lipoproteins, and 24-hour urinary protein excretion determined. Hypertriglyceridemia, elevated VLDL-cholesterol and VLDL-triglycerides were seen at as early as 6 weeks of age in obese rats at a time when other lipoprotein fractions were normal. By 23 weeks, proteinuria developed in obese animals and renal tissue showed increased mesangial matrix, hypercellularity and glomerulosclerosis with lipid deposition noted in the mesangium. All of these abnormalities worsened during the 34 weeks of study at a time when almost all of the total circulating cholesterol was carried by VLDL rather than low-density lipoprotein (LDL), the predominant carrier of circulating cholesterol. These data suggest that increased lipoproteins with atherogenic potential, specifically cholesterol-rich VLDL and triglyceride-rich VLDL particles, correlated positively with the development of renal injury and glomerulosclerosis in obese Zucker rats. They further support a hypothesis that the increased appearance of atherogenic lipoproteins, particularly cholesterol-rich VLDL, may be associated with proteinuria and progressive glomerular injury.
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PMID:Association between very-low-density lipoprotein and glomerular injury in obese Zucker rats. 832 40

Obese spontaneously hypertensive rats (SHR) develop nephropathy with severe proteinuria, but lean littermates do not develop renal disease. Intrarenal angiotensin has been suggested to contribute to nephropathy in other experimental models. We examined the regulation of angiotensin receptors as a reflection of target tissue response to possible changes in the renin-angiotensin system. We visualized angiotensin receptors in kidneys of 6-8-month-old obese SHR and their lean littermates. Both obese and lean rats were hypertensive as determined by tail-cuff or by direct measurement. Histologic studies showed early glomerular sclerosis in obese but not lean rats. Autoradiographic visualization of angiotensin receptor binding sites in both obese and lean SHR showed glomeruli and medullary rays having the highest levels of binding with additional diffuse labeling in cortex and outer medulla. In obese rats, binding was reduced relative to lean littermates, particularly in the medulla, while intense binding in glomeruli was preserved. Loss of receptors did not reflect tissue damage, since the medulla showed no pathological changes. Biochemical assays of the binding of subtype-selective antagonists to 125I-angiotensin sites in intact sections showed that both losartan-sensitive and PD 123319-sensitive sites were decreased in nephrotic obese rats. We conclude that specific binding sites for angiotensin are decreased in obese SHR with early glomerular sclerosis, suggesting that angiotensin receptors may be regulated by pathogenic processes in this model of renal disease.
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PMID:Renal angiotensin receptor mapping in obese spontaneously hypertensive rats. 850 89


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