Neurological and stress related effects of shifting obese rats from a palatable diet to chow and lean rats from chow to a palatable diet

Rats exposed to an energy rich, cafeteria diet overeat and become obese. The present experiment examined the neural and behavioural effects of shifting obese rats from this diet to chow and lean rats from chow to the cafeteria diet. Two groups of male Sprague Dawley rats (n=24) were fed either highly palatable cafeteria diet or regular chow (30% vs. 12% energy as fat) for 16 weeks. Half of each group (n=12) was then switched to the opposing diet while the remainder continued on their original diet. The effects of diet switch on the response to restraint stress were assessed and rats were euthanised nine days after diet reversal. After 16 weeks of cafeteria diet, rats were 27% heavier than controls. Rats switched from chow to cafeteria diet (Ch-Caf) became hyperphagic and had increased dopamine D1, D2 and tyrosine hydroxylase mRNA expression in the ventral tegmental area (VTA) compared to rats switched from cafeteria to chow (Caf-Ch). Caf-Ch rats were hypophagic with significant reductions in white (16%) and brown (32%) adipose tissue mass, plasma leptin (34%) and fasting glucose (22%) compared to rats remaining on the cafeteria diet (Caf-Caf). Caf-Caf rats had an elevated plasma corticosterone response to restraint stress compared to Ch-Caf rats indicating that acute but not chronic consumption of palatable cafeteria diet may protect against stress. Caf-Ch rats had increased corticotropin releasing hormone mRNA expression in the dorsal hypothalamus compared to Ch-Ch rats implying that removal of the palatable diet activated the HPA axis. The results were discussed in terms of the links between palatability of diet, obesity and stress.     

Returning 'cafeteria-fed' rats to a chow diet: negative contrast and effects of obesity on feeding behaviour

Two experiments examined the feeding behaviour and body weight changes of rats returned to a standard chow diet after prolonged periods of cafeteria feeding. In the first, both overweight (ad lib fed) and 'normal' weight (fed a restricted ration of cafeteria foods) cafeteria rats became hypophagic compared to chow-fed rats following their return to chow feeding. However, the overweight rats' hypophagia was initially more severe and was longer lasting. In the second experiment, analysis of meal patterns recorded throughout the first 4 weeks on chow after 26-32 weeks of ad lib cafeteria feeding showed that the hypophagia was due to a reduction in mean meal size (MMS) and meal frequency (MF). Food intake and MMS subsequently recovered to within control levels (by 2-3 weeks), but MF remained persistently low. There was a decrease and then a recovery in eating rate (ER) which paralleled the changes in MMS. The previously cafeteria-fed rats lost only 60% of their excess body weight. These findings are interpreted in terms of a negative contrast effect (changes in MMS and ER) and an inhibitory action of increased adiposity on feeding (affecting mainly MF).     

Effects of a gastric implant on body weight and gastrointestinal hormones in cafeteria diet obese rats

In order to evaluate the effectiveness of a gastric implant in an animal model of dietary obesity, silicone implants (2.5 ml) were inserted into the stomachs of male rats maintained on a chow or "cafeteria" diet. At the time of implantation, the cafeteria fed rats weighed 14% more than chow fed controls. Overweight cafeteria fed animals lost weight in response to the gastric implant, whereas control chow fed animals did not. Both implant groups had significant increases in stomach weights in contrast to sham implant groups, but the increase was much less in the cafeteria diet group. The fasting plasma levels of the gastrointestinal hormones, gastrin and pancreatic polypeptide, and oxytocin (a marker of vagal afferent function) were measured by radioimmunoassay. Cafeteria fed sham or implanted animals had significantly higher fasting levels of plasma oxytocin and gastrin, and significantly lower plasma levels of pancreatic polypeptide than the chow fed groups. These studies demonstrate that the gastric implant has more effect on weight in overweight animals on a palatable mixed diet, perhaps related to both mechanical and neural factors.     

Effect of vitamin A supplemented diet on calcium oxalate renal stone formation in rats

ObjectivesTo study the effect of a vitamin A supplemented diet on calcium-oxalate stone formation in rats and to test its expected action in the dissolution of renal calculi.Material and methodsTwenty-four male Wistar rats were randomly divided into three groups of eight rats each. The first group (group A) received a normal diet for six weeks. The second group (group B) was fed a lithogenic diet by the addition of ethylene glycol 0.5% to drinking water for three weeks then a normal diet for three weeks. The third group (group C) received the same lithogenic diet for three weeks then a vitamin A supplemented diet 20 times the normal amount (5.1 mg/100 g of diet) at the three last weeks. One day before the end of treatment, each animal was placed for 24 h in metabolic cage in order to collect urine samples and determine the urinary parameters.ResultsThe glomerular filtration rate and the urinary excretion of citric acid which fell in group B have been restored in group C.ConclusionsThis study shows that a vitamin A supplemented diet at the rate of 20 times standard ration could improve the renal function by restoring the glomerular filtration rate and by increasing the urinary pH and excretion of citric acid.     

Abresham ameliorates dyslipidemia,hepatic steatosis and hypertension in high-fat diet fed rats by repressing oxidative stress,TNF-α and normalizing NO production

This study was aimed to investigate whether standardized hydroalcoholic extract of abresham (AB) ameliorates dyslipidemia, hepatic steatosis and associated hypertension in rats fed with high-cholesterol/high-fat diet (HFD). HFD (55% calorie from fat and 2% cholesterol) were fed for 45 days to induce dyslipidemia, hepatic steatosis and associated hypertension. After confirmation of hypercholesterolemia (total cholesterol >150 mg/dl) on 30th day, different doses of AB (200–800 mg/kg/day) were administered for next 15 days. HFD administration for 45 days led to cardiometabolic syndrome characterized by significant increase in body weight, total cholesterol, triglyceride, low density lipoprotein cholesterol, TNF-α levels along with decrease in high density lipoprotein cholesterol and serum NO level. Furthermore, HFD resulted in significant increase in systolic arterial pressure, diastolic arterial pressure and mean arterial pressure. In addition, morphological studies revealed hepatic steatosis along with swelling of mitochondria and loss of cristae in hepatocyte and periarteritis in aorta. Treatment with AB for 15 days positively modulated the altered parameters in dose-dependent fashion, though maximum effect was seen at 800 mg/kg. These findings suggest that AB guard against cardiometabolic syndrome in HFD fed rats. It attenuates dyslipidemia, hepatic steatosis and associated hypertension by decreasing oxidative stress, TNF-α and normalizing NO production.     

Effects of early life interventions and palatable diet on anxiety and on oxidative stress in young rats

Early life events can change biochemical, endocrine and behavioral aspects throughout the life of an animal. Since there is a strong relationship between stress, neonatal handling and feeding behavior, the aim of this study was to investigate the effects of these three factors on behavioral parameters (anxiety and locomotion), oxidative stress in brain structures (prefrontal cortex and hippocampus) and on plasma glucose. Nests of Wistar rats were handled (10 min/day), or not (control groups), on days 1-10 after birth. Males from these groups were divided into 4 subgroups: (1) stressed by isolation in childhood (pre-puberty) and with access to a highly palatable diet (2) stressed by isolation and receiving standard lab chow (3) not isolated and receiving a highly palatable diet and (4) not isolated and receiving standard chow. The animals were kept under these conditions for 7 days. Rats receiving the highly palatable diet consumed more food, more calories, gained more weight and had a higher plasma glucose level, but had a lower caloric efficiency than the standard chow groups. Both handling and palatable diet were able to increase food consumption on the first day of isolation. Isolation stress had an anxiogenic effect in the plus maze, which was counteracted by handling. Palatable diet increased time spent in the central area of the open field apparatus and in the open arms of the elevated plus maze, showing an anxiolytic effect. The use of both these conditions, however, does not appear to bring additional protection against the effects of stress during this particular period of life, i.e., pre-puberty. In the prefrontal cortex, handling reduced thiol content and appears to imbalance the antioxidant enzymes system, which is counteracted by a palatable diet. Hippocampus seems to be more sensitive than the prefrontal cortex to early interventions, especially to the highly palatable diet, and both handling and diet appear to imbalance the antioxidant enzyme system. Thus, measurements of antioxidant enzymes activities indicate that handling may endanger some brain structures and that the palatable diet was able to prevent some handling effects on antioxidant enzymes, depending on the brain structure.     

The role of oxidative stress and inflammatory response in high-fat diet induced peripheral neuropathy

ObjectiveEarlier studies suggest that high-calorie diet is an important risk factor for neuronal damage resulting from oxidative stress of lipid metabolism. In our experimental study of rats under high-fat diet, oxidative stress markers and axonal degeneration parameters were used to observe the sciatic nerve neuropathy. The aim of this study is to evaluate the pathophysiology of neuropathy induced by high-fat diet.MethodsA total of 14 male rats (Wistar albino) were randomly divided into two experimental groups as follows; control group (n = 7) and the model group (n = 7); while control group was fed with standard diet; where the model group was fed with a high-fat diet for 12 weeks. At the end of 12 weeks, the lipid profile and blood glucose levels, interleukin-1β (IL-1), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and transforming growth factor-β (TGF-β) levels were studied. Tissue malondialdehyde (MDA), nitric oxide (NO) levels and super-oxide dismutase (SOD), paraoxonase-1 (PON-1) and glutathione peroxidase (GPx) activities were studied. The distal blocks of the left sciatic nerves were evaluated for histomorphological analysis (including mean axon area, axon numbers, nerve fiber diameters, axon diameters, and thickness of myelin sheets).ResultsBody weights, serum glucose and high-density lipoprotein (HDL) levels of rats were found not statistically significantly different compared between the model and the control groups (p > 0.05). Serum cholesterol, triglyceride, TGF-β and TNF-α levels were significantly higher in the model group when compared with the control group (p < 0.05). IL-1 and IL-6 levels were not statistically significantly different compared between the model group and the control group (p > 0.05). The MDA and NO levels and the SOD and GPx activities of the sciatic nerves in model group were statistically significantly higher than the control group (p < 0.05). In addition, the activities of PON-1 were statistically significantly lower in the model group when compared with the control group (p < 0.05). The difference in the total number of myelinated axons between the control group and the model group was not statistically significant (p > 0.05). The nerve fiber diameter and the thickness of the myelin sheet were statistically significantly lower in the model group when compared with the control group (p < 0.05). The axon diameter and area were significantly decreased in the model group when compared with the control group (p < 0.05).ConclusionOur results support that dyslipidemia is an independent risk factor for the development of neuropathy. In addition, we postulated that oxidative stress and inflammatory response may play an important role in the pathogenesis of high-fat diet induced neuropathy.     

Rats with metabolic syndrome resist the protective effects of N-acetyl l-cystein against impaired spermatogenesis induced by high-phosphorus/zinc-free diet

Consumption of relatively high amounts of processed food can result in abnormal nutritional status, such as zinc deficiency or phosphorus excess. Moreover, hyperphosphatemia and hypozincemia are found in some patients with diabetic nephropathy and metabolic syndrome. The present study investigated the effects of high-phosphorus/zinc-free diet on the reproductive function of spontaneously hypertensive rats/NDmcr-cp (SHR/cp), a model of the metabolic syndrome. We also investigated the effects of antioxidant, N-acetyl-l-cysteine (NAC), on testicular dysfunction under such conditions. Male SHR/cp and control rats (Wistar Kyoto rats, WKY) were divided into three groups; rats fed control diet (P 0.3%, w/w; Zn 0.2%, w/w), high-phosphorus and zinc-deficient diet (P 1.2%, w/w; Zn 0.0%, w/w) with vehicle, or high-phosphorus and zinc-deficient diet with NAC (1.5 mg/g/day) for 12 weeks (n = 6 or 8 rats/group). The weights of testis and epididymis were significantly reduced by high-phosphate/zinc-free diet in both SHR/cp and WKY. The same diet significantly reduced caudal epididymal sperm count and motility and induced histopathological changes in the testis in both strains. Treatment with NAC provided significant protection against the toxic effects of the diet on testicular function in WKY, but not in SHR/cp. The lack of the protective effects of NAC on impaired spermatogenesis in SHR/cp could be due to the more pronounced state of oxidative stress observed in these rats compared with WKY.     

Cardiac and renal distribution of ACE and ACE-2 in rats with heart failure

Congestive heart failure is often associated with impaired kidney function. Over-activation of the renin–angiotensin–aldosterone system (RAAS) contributes to avid salt and water retention in heart failure. While the expression of angiotensin converting enzyme (ACE), a key enzyme in the synthesis of angiotensin II (Ang II), is well established, the expression of angiotensin converting enzyme-2 (ACE-2), an enzyme responsible for angiotensin 1–7 generation, is largely unknown. This issue is of a special interest since angiotensin 1–7 counteracts many of the proliferative and hypertensive effects of angiotensin II. Therefore, the present study was designed to investigate the expression of both enzymes in the kidney and heart of rats with heart failure. Heart failure (CHF) was induced in male Sprague Dawley rats (n = 9) by the creation of a surgical aorto-caval fistula. Sham-operated rats served as controls (n = 8). Two weeks after surgery, the animals were sacrificed and their hearts and kidneys were harvested for assessment of cardiac remodeling and ACE and ACE-2 immunoreactivity by immunohistochemical staining. ACE immunostaining was significantly increased in the kidneys (4.34 ± 0.39% vs. 2.96 ± 0.40%, P < 0.05) and hearts (4.57 ± 0.54% vs. 2.19 ± 0.37%, P < 0.01) of CHF rats as compared with their sham controls. In a similar manner, ACE-2 immunoreactivity was also elevated in the kidneys (4.65 ± 1.17% vs. 1.75 ± 0.29%, P < 0.05) and hearts (5.48 ± 1.11% vs. 1.13 ± 0.26%, P < 0.01) of CHF rats as compared with their healthy controls. This study showed that both ACE and ACE-2 are overexpressed in the cardiac and renal tissues of animals with heart failure as compared with their sham controls. The increased expression of the beneficial ACE-2 in heart failure may serve as a compensatory response to the over-activity of the deleterious isoform, namely, angiotensin converting enzyme 1(ACE-1).     

Propolis attenuates cobalt induced-nephrotoxicity in adult rats and their progeny

The aim of this study was to evaluate the biochemical changes in cobalt-exposed rats and to investigate the potential role of Tunisian propolis against the cobalt-induced renal damages. Twenty-four pregnant Wistar rats were divided into four groups and were treated as follows: group 1 (control) received distilled water; group 2 received 350 ppm of CoCl₂ in drinking water; group 3 received 350 ppm CoCl₂ in drinking water and a propolis-supplemented diet (1 g/100 g of diet); group 4 received a propolis-supplemented diet (1 g/100 g of diet) without cobalt. In the cobalt group, a significant decrease in body, absolute and relative weights was noted when compared to controls. The administration of cobalt to pregnant rats from the 14th day of pregnancy until day 14 after delivery resulted in an increased level of renal malondialdehyde, a decreased renal content of glutathione and antioxidant enzyme activities such as superoxide dismutase, catalase and glutathione peroxidase in lactating rats and their pups. A statistically significant increase in plasma urea and creatinine serum levels was seen in treated female rats and their pups. Histopathologically, the cobalt-administration induced degenerative changes in the kidney of lactating rats and their pups. When compared with cobalt-treated rats, those receiving the propolis supplementation (along with cobalt-treatment) had lower malondialdehyde levels, higher antioxidant activities and the cobalt-related histopathological changes in the kidneys were at lower severity.Our results suggested that the propolis might be a potential candidate agent against cobalt-induced nephrotoxicity in adult and juvenile rats when administered to female rats during the late pregnancy and the early postnatal period.     

Attenuation of cyclophosphamide-induced neurotoxicity in rat by yellow dye extract from root of Brimstone tree (Morinda lucida)

Cyclophosphamide is an anticancer and immunosuppressant drug that induces reactive oxygen species (ROS) production, so causing malondialdehyde (MDA) production, which is toxic to cells. This study therefore sought to assess the antioxidant and the protective effect of dietary inclusion (0.5 and 1.0%) of yellow dye from root of Brimstone tree (used to enhance the sensory quality of foods and in folk medicine) on cyclophosphamide-induced oxidative stress in brain. Wistar strain albino rats were placed on diet containing 0.5 and 1.0% yellow dye preparation from root of Brimstone tree for 14 days. Intraperitoneal administration of cyclophosphamide (75 mg/kg of body weight) 24 h before the termination of the experiment caused a significant (P < 0.05) increase in the brain malondialdehyde (MDA) content (147.2%) and serum activities of aspartate aminotransferase (AST) (21.7 UI/l), alanine amino-transferase (ALT) (29.6 UI/l), alkaline phosphatase (43.8UI/l) and total bilirubin (1.7 mg/dl). However, there was a significant decrease (P < 0.05) in the MDA of content of the brain and serum enzyme activities, in those rats fed diet containing the yellow dye in a dose dependent manner. The inhibition of oxidative stress in brain and serum enzymes and metabolites by the dye could be attributed to its high total phenol content and antioxidant activity as typified by its reducing power, free-radical scavenging ability, Fe(II) chelating ability and inhibition of lipid peroxidation. Therefore, dietary inclusion of the yellow dye from root of Brimstone tree could prevent cyclophosphamide-induced oxidative stress in brain and the associated toxicity to the liver.     

Protective effect of lactofermented beetroot juice against aberrant crypt foci formation and genotoxicity of fecal water in rats

The aim of the study was to investigate the effects of beetroot juice fermented by Lactobacillus brevis 0944 and Lactobacillus paracasei 0920 (FBJ) on carcinogen induction of aberrant crypt foci (ACF) in rat colon. N-Nitroso-N-methylurea (MNU) was used as carcinogen, which was administrated intragastrically at a dose of 50 mg/kg on the 23rd and 26th day of the experiment. Additionally, we investigated the cytotoxicity and genotoxicity of fecal water from experimental animals in the Caco 2 cell line, evaluated by MTT/NRU tests and the comet assay, respectively, as well as by the count of bacteria adhered to colon epithelium assessed by fluorescence in situ hybridization and DAPI staining. The experimental rats were divided into four groups based on diet type: basal diet, basal diet supplemented with FBJ, basal diet and MNU treatment, and basal diet supplemented with FBJ and MNU treatment. FBJ significantly reduced the number of ACF in MNU-treated rats (from 55 ± 18 to 21 ± 6). Moreover, the number of extensive aberrations (more than 4 crypts in a focus) decreased from 45 ± 21 to 7 ± 4. Fecal water obtained from rats fed with an MNU-containing diet induced pronounced cytotoxic and genotoxic effects in Caco 2 cells, but FBJ supplementation of the diet abolished these effects. The presence of FBJ in the diet significantly increased the count of bacteria, including Lactobacillus/Enterococcus, adhered to colonic epithelium. In conclusion, supplementation of the diet with lactofermented beetroot juice may provide protection against precancerous aberrant crypt formation and reduce the cytotoxic and genotoxic effects of fecal water.     

Memory and learning behavior in mice is temporally associated with diet-induced alterations in gut bacteria

The ability of dietary manipulation to influence learning and behavior is well recognized and almost exclusively interpreted as direct effects of dietary constituents on the central nervous system. The role of dietary modification on gut bacterial populations and the possibility of such microbial population shifts related to learning and behavior is poorly understood. The purpose of this study was to examine whether shifts in bacterial diversity due to dietary manipulation could be correlated with changes in memory and learning. Five week old male CF1 mice were randomly assigned to receive standard rodent chow (PP diet) or chow containing 50% lean ground beef (BD diet) for 3 months. As a measure of memory and learning, both groups were trained and tested on a hole-board open field apparatus. Following behavioral testing, all mice were sacrificed and colonic stool samples collected and analyzed by automated rRNA intergenic spacer analysis (ARISA) and bacterial tag-encoded FLX amplicon pyrosequencing (bTEFAP) approach for microbial diversity. Results demonstrated significantly higher bacterial diversity in the beef supplemented diet group according to ARISA and bTEFAP. Compared to the PP diet, the BD diet fed mice displayed improved working (P = 0.0008) and reference memory (P < 0.0001). The BD diet fed animals also displayed slower speed (P < 0.0001) in seeking food as well as reduced anxiety level in the first day of testing (P = 0.0004). In conclusion, we observed a correlation between dietary induced shifts in bacteria diversity and animal behavior that may indicate a role for gut bacterial diversity in memory and learning.     

Preventive effect of a galactoglucomannan (GGM) from Dendrobium huoshanense on selenium-induced liver injury and fibrosis in rats

This study was carried out to investigate the preventive effects of galactoglucomannan (GGM), a homogeneous polysaccharide from Dendrobium huoshanense, on liver injury and fibrosis induced by sodium selenite. Sprague–Dawley rats injected subcutaneously with sodium selenite at the dosage of 3.28 mg kg^?1 b. wt. were set as the model groups. Rats treated with sodium selenite at the dosage of 3.28 mg kg^?1 b. wt. and GGM at 50–200 mg kg^?1 b. wt. were set as the prevention groups. Biochemical and histological analysis showed that GGM significantly ameliorated selenite-induced liver injury and fibrosis in rats. Oral administration of GGM effectively attenuated the toxicity of selenite to liver tissue, which was judged both by the decreased activities of serum hepatic enzymes, including alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH), and by liver histopathological examination. Meanwhile, GGM also reduced the levels of H₂O₂ and malondialdehyde (MDA), elevated the levels of GSH, restored the fluidity of hepatic plasma membrane, and retained the activities of endogenous enzymes including superoxide dismutase (SOD), catalase (CAT) and glutathione S-transferase (GST). The prevention of selenite-induced liver injury and fibrosis by GGM was further supported by the reduced expression of transforming growth factor-β1 (TGF-β1) and type I collagen. These results suggested that GGM may be developed into a novel antifibrotic agent for the prevention of liver injury and fibrosis.     

The effect of rosmarinic acid on 1,2-dimethylhydrazine induced colon carcinogenesis

This study was carried out to investigate the chemopreventive potential of rosmarinic acid (RA) against 1,2-dimethylhydrazine (DMH) induced rat colon carcinogenesis by evaluating the effect of RA on tumour formation, antioxidant enzymes, cytochrome P450 content, p-nitrophenol hydroxylase and GST activities. Rats were divided into six groups and fed modified pellet diet for the entire experimental period. Group 1 served as control, group 2 received RA (10 mg/kg b.w.). Groups 3–6 were induced colon cancer by injecting DMH (20 mg/kg b.w.) subcutaneously once a week for the first four weeks (groups 3–6). In addition, RA was administered at the doses of 2.5, 5 and 10 mg/kg b.w. to groups 4–6 respectively. DMH treated rats showed large number of colonic tumours; decreased lipid peroxidation; decreased antioxidant status; elevated CYP450 content and PNPH activities; and decreased GST activity in the liver and colon. Supplementation with RA (5 mg kg/b.w.) to DMH treated rats significantly decreased the number of polyps (50%); reversed the markers of oxidative stress (21.0%); antioxidant status (38.55%); CYP450 content (29.41%); and PNPH activities (21.9%). RA at the dose of 5 mg/kg b.w. showed a most pronounced effect and could be used as a possible chemopreventive agent against colon cancer.     

A new metaphyseal bone defect model in osteoporotic rats to study biomaterials for the enhancement of bone healing in osteoporotic fractures

The intention of this study was to establish a new critical size animal model that represents clinically relevant situations with osteoporotic bone status and internally fixated metaphyseal defect fractures in which biomaterials for the enhancement of fracture healing in osteoporotic fracture defects can be studied. Twenty-eight rats were ovariectomized (OVX) and treated with a calcium-, phosphorus-, vitamin D3-, soy- and phytoestrogen-free diet. After 3 months Dual-energy X-ray absorptiometry measurements showed statistically significant reductions in bone mineral density of the spine of ?25.9% and of the femur of ?21.3% of the OVX rats compared with controls, confirming osteoporosis in the OVX rats. The OVX rats then underwent either 3 or 5 mm wedge-shaped osteotomy of the distal metaphyseal area of the femur that was internally stabilized with a T-shaped mini-plate. After 42 days biomechanical testing yielded completely unstable conditions in the 5 mm defect femora (bending stiffness 0 N mm^?2) and a bending stiffness of 12,500 N mm^?2 in the 3 mm defects, which showed the beginning of fracture consolidation. Micro-computed tomography showed statistically significant more new bone formation in the 3 mm defects (4.83 ± 0.37 mm²), with bridging of the initial fracture defect area, compared with the 5 mm defects (2.68 ± 0.34 mm²), in which no bridging of the initial defect was found. These results were confirmed by histology. In conclusion, the 5 mm defect can be considered as a critical size defect model in which biomaterials can be tested.     

Lack of diet-induced thermogenesis in brown adipose tissue of obese medial hypothalamic-lesioned rats

Radiofrequency heat lesions were made in the medial hypothalamus of 12-week old male and female Holtzman rats. Two to three days later rats were offered a palatable cafeteria diet in addition to chow or were fed chow alone for the next 3-4 weeks. Male lesioned rats were only slightly hyperphagic on the chow diet and gained little extra weight. When fed the cafeteria diet, energy intake of male lesioned rats almost doubled in comparison with chow-fed lesioned rats and a very rapid extra weight gain occurred. Despite the marked hyperphagia, thermogenesis in brown adipose tissue was suppressed in the cafeteria-fed lesioned rats, as indicated by low mitochondrial guanosine diphosphate (GDP) binding. In female rats, lesions induced much greater hyperphagia and body weight gain than in male rats, particularly when they ate the cafeteria diet. Again, thermogenesis in brown adipose tissue was suppressed in the cafeteria-fed female lesioned rats. The proportion of energy derived from carbohydrate was not altered by the cafeteria diet in either male or female rats, whether lesioned or not, but there was an increase in the proportion of energy derived from fat at the expense of protein. No sex differences in food selection were observed. The accumulation of body fat was always greater in female lesioned rats than in male lesioned rats for similar food intakes. It is concluded that medial hypothalamic lesions prevent the normal occurrence of diet-induced thermogenesis in brown adipose tissue despite extreme overeating by the rats of a palatable cafeteria diet.     

Kinetics of the electrocardiographic changes after permanent coronary occlusion in rats: Relationship with infarct size

The electrocardiogram (ECG) has been a useful tool to identify ischemia in humans and laboratory animals. Previous ECG studies showed that presence of pathological Q waves in lead DI in rats submitted to ligature of the left coronary artery (LCA) is a good predictor of successful myocardial infarction (MI). This study aimed to determine the sensitivity and the specificity of these ECG findings to predict successful MI. Male Wistar rats were submitted to surgical ligature of the LCA (N = 86) or sham-operation (SO, N = 16). ECG was recorded under halothane/ether anesthesia before surgery and 1, 3, 5, 7, and 15 days later. MI was determined by the presence of a transmural fibrous scar. Sixty-nine rats survived and 60 showed fibrous scar indicating a successful production of MI (18 and 42 animals were analyzed 1 or 15 days after MI, respectively). Twenty-four hours after, Q amplitude was linearly related to infarct size (r = ?0.778; P < 0.01), but not 15 days after (r = ?0.416; P > 0.05). In 53 out of 60 rats with transmural scar, Q wave in lead DI was identified in the ECG. Absence of Q wave occurred in 7 animals. The sensitivity was 88% (CI₉₅ = 83–93%). Nine animals submitted to coronary ligature did not show infarct scar. One of these animals, however, showed Q wave in DI, indicating a specificity of 77% (CI₉₅ = 65–104%). In conclusion, ECG can be used as a reliable tool to identify MI and can be used to predict the infarct size as earlier as 1 day after LCA ligation in rats.     

Adverse effects in kidney function,antioxidant systems and histopathology in rats receiving monosodium glutamate diet

We investigated the effects of adding of monosodium glutamate (MSG) to a standard diet on oxidative stress in kidney, nitric oxide excretion, renal ions handling and blood pressure. We examined the association of these changes with the effects on renal histology. The study was performed on male Wistar rats (5 weeks old) divided into 3 groups: 1) MSG group were fed a diet supplemented with 3 g of MSG/kg b.w./day, five days a week, and spontaneous ingestion of a 1% MSG solution during 16 weeks; 2) NaCl group were fed a diet with NaCl (1 g/kg b.w./day) and 0.35% NaCl solution permanently alone at the same frequency and time; 3) control group were fed the normal chow and tap water. Sodium, potassium, calcium, phosphorus, creatinine, protein and nitric oxide excretion were analyzed in urine. We utilized clearance techniques to examine glomerular filtration rate and cortical renal plasma flow. We determined the oxidative state and the histopathological changes of renal tissue.Following MSG treatment, absolute and fractional sodium and potassium excretion decreased although there was hyperfiltration. The MSG group showed similar increase in blood pressure than the NaCl group, but nitric oxide excretion was significantly reduced. Although no increase in lipid peroxidation was verified, its observed alteration in the reduced glutathione/oxidized cycle and their enzymes GPx and GR. These changes were accompanied by alterations histological both glomerular as well as tubular level and by interstitial fibrosis with mononuclear cells accumulation.These results indicate that the addition of MSG in the diet decreases the excretion of Na, K and water with hyperfiltration. NaCl retention that leads to hypertension was accompanied by renal pathologic changes, intrarenal oxidative stress and reduction of nitric oxide excretion.     

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.