Sex differences in the effects of high-fat feeding on behavior and carcass composition

Male and female Sprague-Dawley rats were fed a high-fat diet (40% by weight) for 11 weeks beginning at 70–80 days of age. At the end of the 11th week, high-fat fed rats of both sexes were significantly heavier than chow-fed controls. All rats were then food deprived and were trained to bar-press in an operant chamber for Noyes pellets. Testing on fixed ratio (FR) schedules started when their body weights reached 85% of pre-deprivation levels and they pressed bar steadily. At the end of operant testing, all rats were refed their previous diet until body weights returned to pre-deprivation levels. The animals were then sacrificed. Fat pads from retroperitoneal, inguinal and gonadal regions were dissected out and cellularity determined. Carcass composition was analyzed by chemical methods. On the operant apparatus, the high-fat fed female rats (F-HF) behaved more like VMH lesioned obese rats, i.e. decreased bar pressing responses when compared with controls. No difference in operant responding was found between males fed high-fat diet and chow. Fat cell number and size were increased in retroperitoneal and inguinal fat pad for rats fed high-fat diet. In gonadal pads, only cell size was increased. Females on the high-fat diet had higher percentages of body fat than males on the high-fat diet. The behavioral difference in F-HF rats could be attributed to their higher adiposity. The results support previously reported findings on the behavior and adipose tissue cellularity of dietary obese rats.     

Histological and histochemical assessment of the effects of a single dose adriamycin on fetal rat kidney

Adriamycin (ADR) induces nephritic syndrome (NS) in adult rats. Therefore, effects of ADR in a single dose of 5mg/kg body weight given intraperitoneally to the mothers at 4 weeks before pregnancy were assessed on fetal rat kidneys in the present study. It induces increased amounts of PAS(+)-positive mesangial matrix, glomerulosclerosis, dilatation of the urinary space and thickening of basement membranes in glomeruli. In tubules, it damages or completely destroys epithelial cells, it induces dilatation of the tubular lumen and disintegration of the brush border. Changes in fetal rat kidney as observed light microscopically appeared to be similar to those described in kidneys of adult rats with NS induced by adriamycin, but were less distinct.     

Acute exposure to a high-fat diet alters meal patterns and body composition

Weight gain and adiposity are often attributed to the overconsumption of unbalanced, high-fat diets however, the pattern of consumption can also contribute to associated body weight and compositional changes. The present study explored the rapid alterations in meal patterns of normal-weight rats given continuous access to high-fat diet and examined body weight and composition changes compared to chow fed controls. Ten Long-Evans rats were implanted with subcutaneous microchips for meal pattern analysis. Animals were body weight matched and separated into two groups: high-fat or chow fed. Each group was maintained on their assigned diet for nine days and monitored for 22 h each day for meal pattern behavior. Body weight was evaluated every other day, and body composition measures were taken prior and following diet exposure. High-fat fed animals gained more weight and adipose tissue than chow fed controls and displayed a reduced meal frequency and increased meal size. Furthermore, meal size was significantly correlated with the gain of adipose tissue. Together, these results suggest that consumption of a high-fat diet can rapidly alter meal patterns, which in turn contribute to the development of adiposity.     

Rats Fed Diets with Different Energy Contribution from Fat Do Not Differ in Adiposity

ObjectiveTo determine whether rats reaching the same body mass, having been fed either a low-fat (LFD) or a high-fat diet (HFD), differ in white adipose tissue (WAT) deposition.MethodsIn experiment 1, 22 Sprague-Dawley rats of the same age were divided into 11 rats with body mass below the batch median and fed a HFD, and 11 above the median and fed a LFD. In experiment 2, 20 Sprague-Dawley rats of the same age and starting body mass were randomised to either a HFD or LFD. When all groups reached similar final body mass, WAT was quantified using magnetic resonance imaging (MRI), dissection, and plasma leptin.ResultsIn experiment 1, both groups reached similar final body mass at the same age; in experiment 2 the HFD group reached similar final body mass earlier than the LFD group. There were no significant differences in WAT as assessed by MRI or leptin between the HFD and LFD groups in both experiments. Dissection revealed a trend for higher retroperitoneal and epididymal adiposity in the HFD groups in both experiments.ConclusionsWe conclude that at similar body mass, adiposity is independent of the macronutrient composition of the feeding regimen used to achieve it.Key Words: High-fat diet, Low-fat diet, MRI, Leptin     

Studies of the pathogenetic role of humoral antibodies reacting with subcellular organ antigens: II. Passive immunization of rats with anti-rat rabbit immune sera

Immunizing injections of rat liver and kidney mitochondrial fractions were administered to rabbits, and the effects of injecting the antisera into rats were investigated. Rats receiving antiserum to rat liver mitochondria showed impaired clearance of sulphobromphthalein, and developed hepatic fibrosis which in one animal progressed to cirrhosis. There was no increase in albuminuria and the kidneys showed no histological differences from those of control rats receiving normal rabbit serum. Renal changes were virtually confined to rats receiving antiserum to rat kidney mitochondria: these animals excreted increased amounts of protein and showed increased cellularity of the glomeruli, tubular casts and hydropic changes in the tubular epithelium. The significance of these findings is discussed.     

Induction of glomerulosclerosis by dietary lipids. A functional and morphologic study in the rat

Clinical and experimental data indicate that glomerular function and morphology may be influenced by plasma lipids. In familial lecithin-cholesterol-acyltransferase (LCAT) deficiency and in Fabry's disease, lipids accumulate in glomeruli and are assumed to induce sclerosis. The present study was undertaken to examine if dietary lipids could exert effects on the glomeruli of normal, unilaterally nephrectomized rats, and of rats with two-kidney, one clip (2-K,1C) hypertension. In rats with two kidneys on a diet rich in fat and cholesterol, cholesterol concentrations in very low density lipoproteins increased. In these rats the number of glomeruli with sclerotic foci was significantly higher than in rats on a low fat, cholesterol free diet. After 6 months on the diet the percentage of glomeruli with sclerosis (SC) was 13.2 +/- 4.1 (N = 9) in rats with a cholesterol diet and 1.8 +/- 0.6 (N = 11) in control rats (p less than 0.05). The fat and cholesterol diet exacerbated glomerular lesions in the remnant kidney model of uninephrectomized rats. The sclerosis in rats with only one kidney was 38.2 +/- 9.5 (N = 6) on a cholesterol diet compared with 8.7 +/- 3.0 (N = 6) in control rats after 6 months (p less than 0.05). After 3 to 4 months on a fat rich diet cholesterylester was increased in isolated glomeruli. The composition of the dietary lipids influenced the development of glomerular lesions. A linseed oil diet that is rich in unsaturated fatty acids, especially linolenic acid, did not cause major plasma lipid abnormalities and was accompanied by a low sclerosis (1.2 +/- 0.3; N = 9) for rats with two kidneys. In rats with chronic 2-K, 1C hypertension the percentage of glomeruli with partially sclerosed tufts in the unclipped kidney was significantly higher on a fat and cholesterol diet (F) than on a control diet (N) (SC: diet F 31.0 +/- 4.0, N = 13; diet N 12.2 +/- 2.6, N = 12; P less than 0.05). In the clipped kidney, protected against the arterial hypertension, only an increased number of glomeruli with mesangial expansion was noted in rats with the cholesterol diet. Glomerular hemodynamic factors seem to play an important pathogenetic role in the induction of glomerular sclerosis by a lipid rich diet. The fact that dietary lipids can aggravate glomerular lesions in states of arterial hypertension and nephron loss may have implications for the progression of renal disease in humans.     

Effects of age and dietary restriction on the kidney glomeruli of mice: Observations by scanning electron microscopy

A study was undertaken to examine, by scanning electron microscopy (SEM), the kidney glomeruli of control mice 1 mo, 10 mo, and 24 mo of age, as well as dietarily restricted mice 10 mo and 24 mo of age. One month old female C57BL/6J mice were offered one of the following: (1) a control diet containing 24% protein fed ad lib; (2) the control diet fed on alternate days (intermittently fed); or (3) a diet containing 4% protein fed ad lib. Animals were sacrificed, by aldehyde perfusion at 1 mo, 10 mo, and 24 mo of age. The kidneys were sliced and prepared for SEM. There was a significant age-related increase in glomerular diameter and amount of microvilli on the podocyte surface (microvillus index). Although the diameters of the podocytes increased approximately 20% with age, these differences were not statistically significant. Feeding a 4% protein diet resulted in smaller diameters of glomeruli and podocytes as well as smaller microvilli indices as compared to those of control animals. Although similar differences were observed in the kidneys of intermittently fed animals, only the microvillus index was statistically significant. Therefore, dietary manipulations, which have been shown to increase life span, result in marked morphological differences when compared to control animals.     

Insulin-induced hyperphagia in alloxan-diabetic rats fed a high-fat diet.

Alloxan-diabetic rats fed a standard, low-fat diet lost body weight and were hyperphagic; those fed a high-fat diet lost comparable amounts of weight, but did not overeat compared to normal animals. When given injections of protamine-zinc insulin, all diabetic rats gained weight; however, while those fed the low-fat reduced food intake from elevated levels, diabetics fed the high-fat diet became hyperphagic. Diabetic rats maintained on a high-fat diet increased food intake during long-term insulin treatment sooner and to a greater extent than normal controls. These findings are interpreted in light of the effects of insulin on storage and supply of metabolic fuels.     

The pyridoindole antioxidant stobadine attenuates histochemical changes in kidney of streptozotocin-induced diabetic rats

The aim of the present study was to investigate the effects of dietary supplementation with the pyridoindole antioxidant stobadine on histochemical parameters in kidney of streptozotocin-induced diabetic rats. Diabetic male Wistar rats were fed a standard diet or a diet supplemented with stobadine (0.05% w/w) for 24 weeks. The diabetic state was characterized by significantly elevated plasma levels of glucose and glycated hemoglobin, severe reduction of total body weight and relatively enlarged kidneys. Kidney alkaline phosphatase activity was not changed by diabetes. Activity of 5'-nucleotidase, K(+)-dependent p-nitrophenylphosphatase, ATPase and mitochondrial succinic dehydrogenase were markedly decreased in kidneys of diabetic rats. In contrast, activity of beta-hydroxybutyrate dehydrogenase was moderately increased in kidney of diabetic rats as compared to controls. Long-term treatment of diabetic animals with stobadine attenuated histochemical changes in kidney tissue.     

Effects of energy intake on type 1 plasminogen activator inhibitor levels in glomeruli of lupus-prone B/W mice.

Calorie restriction (CR) and/or reduced energy intake ameliorates the progression of autoimmune renal disease in (NZB x NZW)F1 (B/W) female mice and increases life span. Like other forms of glomerulonephritis, the lupus-like kidney disease observed in these animals is frequently accompanied by glomerular deposition of fibrin and increased accumulation of mesangial matrix. Because alterations in plasminogen activator inhibitor type 1 (PAI-1) expression or function may be involved in both fibrin deposition and accumulation of extracellular matrix, we have studied the effects of CR on the expression of PAI-1 in kidneys from female B/W mice fed either ad libitum or on a 40% CR diet. By immunohistochemistry and immunoblotting, we found that the glomerular levels of PAI-1 antigen were highest in older ad lib fed animals with more advanced glomerular disease. Increased levels of PAI-1 protein were paralleled by increased levels of PAI-1 mRNA in total RNA extracted from renal cortex and in diseased glomeruli as detected by in situ hybridization. CR diminished the accumulation of PAI-1 protein and reduced the expression of PAI-1 mRNA. Thus, glomeruli from animals fed ad lib showed much greater deposition of PAI-1 protein, increased expression of PAI-1 mRNA, and more severe histological abnormalities than animals on a CR diet. The differences between CR and ad lib animals were more pronounced in animals studied at 9 to 10 months versus those at 3 to 4 months of age. These observations indicate that the ameliorating effects of CR include diminished PAI-1 gene expression and decreased localization of PAI-1 in glomeruli.     

Alteration of Connexin43 expression in a rat model of obesity-related glomerulopathy

It is accepted that alteration of connexin43 (Cx43) expression in glomeruli is a common pathological response in several forms of kidney diseases. To date, however the change of the Cx43 expression in obesity-related glomerulopathy (ORG) has not been reported. In this study, the alteration of Cx43 expression in the glomeruli of rat with ORG was defined. Five-week-old rats were fed with high-fat diet for 18 weeks to establish the ORG model, then the histological change of glomeruli, the foot process effacement of podocyte, the markers for podocyte injury (nephrin,podocin and WT1) and Cx43 expression in glomeruli were examined respectively. The results demonstrated metabolic disorder, hyperinsulinemia, systemic inflammation and microalbuminuria in ORG rats. There was significant hypertrophy, glomerular expansion and inflammatory cell infiltration in the kidney of ORG rats compared to the control group. Significant foot process effacement of the podocyte in the glomeruli, nephrin loss and density reduction were shown in the ORG rats, and Cx43 expression was significant upregulated in glomeruli of ORG rats compared to the control group. The results indicate the correlation of overexpressed Cx43 with the obesity related renal inflammation and suggest that Cx43 might be a potential target in the development of obesity related glomerulopathy.     

Rats with hypothalamic knife cuts overeat an unpalatable diet

Female rats with bilateral parasagittal knife cuts between the ventromedial and lateral hypothalamus were fed a demonstrably unpalatable 0.4% quinine high-fat diet. These rats overate and maintained their body weights significantly above those of same-diet control animals. These results are similar to previous findings in this laboratory obtained from rats with ventromedial hypothalamic lesions.     

Histopathology and apoptosis in an animal model of reversible renal injury

High adenine phosphate (HAP) diet serves as an animal model of chronic renal failure (RF). Induction of RF and establishment of end organ damage require long exposure periods to this diet. Previously, we have shown that RF is reversible after diet cessation even after protracted administration. In this study, we explored the underlying renal changes and cellular pathways occurring during administration and after cessation of the diet. Kidneys were obtained from rats fed HAP diet for 7 weeks, and from rats fed HAP diet followed a 10 week recovery period on normal diet. The kidneys of HAP diet group were significantly enlarged due to tubular injury characterized by massive cystic dilatation and crystal deposition. Kidney injury was associated with markers of apoptosis as well as with activation of apoptosis related pathways. Diet cessation was associated with a significant reduction in kidney size, tubules diameter, and crystals deposition. The recovery from renal injury was coupled with regression of apoptotic features. This is the first study showing the potential reversibility of long standing RF model, allowing optimal evaluation of uremia-chronic effects.     

Dietary influences on the acute effects of anorectic drugs

The effects of acute administration of d-amphetamine sulfate (0.0, 0.5, 1.0 and 2.0 mg/kg) and dl-fenfluramine hydrochloride (0.0, 1.5, 3.0 and 6.0 mg/kg) on food intake were examined in male Sprague-Dawley rats fed either a high-carbohydrate diet (carbohydrate equaled 65% of total calories) or a high-fat diet (fat equaled 65% of total calories). Animals were given ad lib access to the diets throughout the experiment. Drug injections were given at 0900 on experimental days and food intakes were measured at 1, 3 and 6 h postinjection. Amphetamine led to dose-related decreases in food intake for animals on both diets. The effects of amphetamine were most noticeable at 1 and 3 h postinjection. No differences in amphetamine's effects on food intake were found as a function of diet. Fenfluramine injections also led to dose-related reductions in food intake for animals in both dietary conditions. In contrast to amphetamine, however, fenfluramine led to greater reductions in food intake for rats fed the high-fat diet than for rats fed the high-carbohydrate diet. These data demonstrate that dietary variables must be considered when evaluating the anorectic actions of psychopharmacological agents.     

Lack of diet-induced thermogenesis following lesions of paraventricular nucleus in rats

The effects of electrolytic lesions in the hypothalamus paraventricular nucleus were studied in adult male and female Sprague-Dawley rats, fed different diets, consisting of either palatable human food plus chow (cafeteria diet) or chow alone. The results showed that both cafeteria diet and lesions induced an increase in energy intake and weight gain in rats of both sexes. Oxygen consumption rate and colonic temperature were significantly decreased by lesions, while cafeteria diet increased the same parameters only in intact animals. The lesion decreased weight, protein and DNA, and temperature of brown adipose tissue, while cafeteria diet increased the values considered in brown adipose tissue of sham-injured rats, but not in lesioned animals. The response to norepinephrine administration was significantly greater in intact rats and those fed cafeteria diet. The results suggest that the larger body weight gain observed in lesioned rats, particularly evident in rats fed cafeteria diet, is partly due to the disappearance of diet-induced thermogenesis that depends on the reduced mass and functional activity of brown adipose tissue.     

Progressive passive Heymann nephritis in the rat

Progressive passive Heymann nephritis was produced in rats by simultaneous intravenous injections of heterologous antirat glomerular basement membrane antiserum and heterologous antirat kidney tubular fraction 3 antibody. The animals were killed at 16 weeks by which time approximately one-half of them were severely proteinuric. The glomeruli showed beaded immune deposits around the capillaries by immunofluorescence, and on electron microscopy osmiophilic deposits were noted in the subepithelial zones and within the glomerular basement membrane. The lesion resembled that of severe Heymann nephritis. gamma-Globulin eluted from the kidneys contained an autologous IgG that reacted with the brush border region of the renal proximal tubules of normal rats. This component was present in proteinuric and nonproteinuric animals. It is concluded that the progression results from the development of autoantibodies to the tubular nephritogenic antigen and the proteinuria is related to increasing deposition of immune complexes in the glomeruli.     

Demonstration of an intrinsic renal adaptation for K+ conservation in short-term K+ depletion

Renal potassium conservation occurs within 3 days of potassium deprivation by a mechanism that appears to be independent of mineralocorticoids and sodium and anion excretion. To examine whether the mechanism involves an intrinsic renal adaptation, urinary potassium excretion was measured in isolated perfused kidneys from rats maintained on a normal or K+-free diet for 3 days. Perfusions were carried out with a K+ concentration that averaged 3.5 mM and with glucose (5 mM) as the only substrate. Both absolute (UKV) and fractional K+ excretion (FEK) were substantially less in kidneys from animals on K+-free diets compared with controls. These differences in K+ excretion were not explained by changes in GFR, urine flow rate, urine pH, or sodium, chloride, or ammonium excretion. The K+ content of renal tissue was not different in the perfused and nonperfused kidneys from rats receiving K+-free diets compared with controls. Suppression of K+ excretion by amiloride (10(-4) M) suggested that, as in vivo, tubular secretion of K+ in the perfused normal kidney accounts for 90% of the urinary K+ excretion and that tubular K+ secretion is reduced in isolated kidneys from animals on a K+-free diet. Further studies of isolated kidneys from adrenalectomized (ADX) rats receiving aldosterone and dexamethasone replacement and fed a normal or K-free diet also revealed significantly lower UKV and FEK in kidneys from animals on K+-free diets. K+ content of renal tissue was not different in the ADX animals on a K+-free diet compared with ADX rats on normal K+ intake. These studies indicate that within 72 h of dietary K+ deprivation an intrinsic renal adaptive process to conserve potassium is activated that is independent of renal potassium content, aldosterone, and urinary factors that can alter K+ excretion such as flow, pH, ammonium, sodium, and anions. This regulatory mechanism, which has a substantial influence on potassium excretion, remains to be elucidated.     

Hypophagia following dietary obesity

Two experiments examined the hypophagia that occurs when rats are switched from a high-fat to a low-fat diet. In the first experiment, rats fed a high-fat diet for eight weeks weighed 79 g more than rats fed a low-fat diet. Removal of the high-fat diet led to reduced food intake for at least four weeks. Reducing the body weight of the rats by a 24 hour fast did not alter the time course of the hypophagia. Plasma levels of free glycerol, free fatty acids and ketones were elevated during and after feeding the high-fat diet; suggesting that feeding a high-fat diet increases fat oxidation even after the high-fat diet is withdrawn. In the second experiment, feeding rats the high-fat diet for four weeks increased body weight and body fat. Starving the rats for two days after feeding the high-fat diet did not alter subsequent hypophagia and did not alter the percentage of body fat. This pattern of results is similar to that previously seen following termination of obesity-inducing insulin treatment. The results are consistent with the idea that a persistent increase in fat oxidation is responsible for the hypophagia.     

Long-term effects of exogenous leptin on body weight and fat in post-obese female rats.

This study was designed to test the hypothesis that short-term leptin infusion during the post-obese refeeding phase of weight-reduced rats would reduce the rate of weight regain and, as a result, reduce the final body weight and fat content in weight-reduced rats. Ninety-six female Wistar rats were divided into four groups: (1) LFCON (low-fat control) group: Rats in this group were fed the control low-fat (LF) diet ad lib for the entire study period. (2) HFCON (high-fat control) group: Rats in this group were fed the high-fat (HF, 40% fat) diet ad lib for the study period. (3) HFRLP (high-fat fed, weight-reduced, leptin treatment) group: Obese rats in this group were weight-reduced and received leptin infusion for 2 weeks (miniosmotic pumps, 0.5 microg/kg/day) during the post-obese refeeding period. (4) HFRSM (high-fat fed, weight-reduced, sham control) group: Rats in this sham-control group were treated the same as the rats in the HFRLP group with the exception that no leptin was actually infused during the first 2 weeks of refeeding period. The results demonstrated that 2 weeks of leptin treatment during the early refeeding phase did not prevent weight regain in weight-reduced rats, but it significantly reduced body fat content in these rats as compared to ad lib fed obese control rats. One cycle of weight reduction and regain did not alter the body weight and body fat content in HFRSM rats when compared to obese control rats. Therefore, leptin treatment was effective in reducing body fat content in post-obese rats for up to 7 weeks, but the long-term effect of short-term leptin treatment needs to be further examined.     

Prevention of Kidney Haemorrhagic Necrosis of Choline-Deficient Rats by α-Methyldopa Treatment

In a previous report from our laboratory we have shown a marked increase in the levels of renal catecholamines in choline-deficient rats in comparison to choline-supplemented animals, while the content of acetylcholine remained unchanged. Since the changes in tissue catecholamines occurred before kidney lesions developed, we have suggested that an imbalance between sympathetic and parasympathetic systems plays an important role in the pathogenesis of renal injury in choline-deficient rates, this imbalance being the result of an excess of catecholamines in the kidneys. A series of experiments was then planned to explore this theory further by administering adrenergic blocking agents in an attempt to prevent the development of the renal injury in choline deficiency. We report here our results on the administration of α-methyldopa, a drug that depletes the tissue stores of catecholamines, to choline-deficient and choline-supplemented rats. Young male Wistar rats were divided at random into 4 groups: Group CS, fed a choline-supplemented diet; Group CS + D, fed a choline-supplemented diet and treated with α-methyldopa; Group CD, fed a choline-deficient diet; and Group CD + D, fed a cholinedeficient diet and treated with α-methyldopa. The appropriate groups received daily i.p. injections of α-methyldopa (300 mg/kg body wt). The kidneys of all surviving rats were studied grossly and histologically, and the levels of noradrenaline and adrenaline determined. All animals from Control Groups CS and CS + D showed essentially normal kidneys on gross and light microscopic examination. On the other hand, CD rats showed marked renal injury, while the kidneys lesions of CD + D animals were significantly less pronounced than those of rats from Group CD. The total content of noradrenaline and adrenaline in the kidneys of CD + D and CD rats were not statistically different, although the CD + D animals tended to have lower levels of catecholamines. The content of noradrenaline and adrenaline of rats from Group CD was significantly higher than the corresponding values in CS rats. Also, the total content of renal noradrenaline of CD + D animals was found to be unaltered when compared to that of CS rats, while their content of adrenaline was found to be higher than the corresponding value in CS group. The noradrenaline levels of CS and CS + D rats were similar, but the latter group had a higher renal adrenaline content than the former. These findings, besides confirming our previous observations, clearly show that α-methyldopa afforded a protective effect against the renal injury of choline deficiency, thus giving strong additional support to the theory that the kidney haemorrhagic necrosis of choline deficiency in young rats is probably due to an autonomic imbalance.