Adaptive responses of 25-hydroxyvitamin D3 1-alpha hydroxylase expression to dietary phosphate restriction in young and adult rats

Regulation of vitamin D metabolism alters with age. The present study is undertaken to investigate if the loss of renal 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) production in response to dietary phosphate (P) restriction in adult rats is due to an alteration in the renal expression of 25-hydroxyvitamin D(3) 1-alpha hydroxylase (1-OHase). Young (4-6 weeks old) and adult (12-14 weeks old) male Sprague Dawley rats were fed either normal P (NPD) or low P diet (LPD) for 0-5 days. Basal expression of 1-OHase protein was higher in adult rats. Young rats, but not adult rats, significantly increased 1-OHase protein and mRNA expressions in response to LPD in a time-dependent manner. To determine if the stability of renal 1-OHase protein changes with LPD feeding, young and adult rats fed either NPD or LPD for 5 days were injected intravenously with cycloheximide (CHX), a protein synthesis inhibitor. CHX decreased 1-OHase protein expression in young rats fed NPD. However, CHX did not alter 1-OHase protein expression in young rats fed LPD nor in adult rats fed either diet. The results indicate that the stability of renal 1-OHase protein increased with age and that LPD increased its stability only in young rats.     

Effect of ischemia reperfusion on sodium-dependent phosphate transport in renal brush border membranes

The effect of ischemia induced acute renal failure (ARF) on the transport of phosphate (Pi) after early (15-30 min) and prolonged (60 min) ischemia in the brush border membrane vesicles (BBMV) from rat renal cortex was studied. Sodium-dependent transport of Pi declined significantly and progressively due to ischemia. Western blot analysis of BBM from ischemic rats showed decreased expression of NaPi-2. A compensatory increase was observed in Pi uptake in BBMV from contralateral kidneys. There was no significant difference in NaPi-2 expression between BBMV from sham and contralateral kidneys. Early blood reperfusion for 15 min after 30 min ischemia caused further decline in Pi uptake. Prolonged reperfusion for 120 min caused partial reversal of transport activities in 30-min ischemic rats. However, no improvement in the transport of Pi was observed in 60-min ischemic rats after 120 min of blood reperfusion. Kinetic studies showed that the effect of ischemia and blood reperfusion was dependent on the V_max of the Na-Pi transporter. Western blot analysis showed increased expression of NaPi-2 in the BBMs from ischemia-reperfusion animals. Further, a shift in the association of Na ions to transport one molecule of Pi was observed under different extracellular Na concentrations [Na]_o. Feeding rats with low Pi diet and/or treatment with thyroid hormone (T3) prior to ischemia resulted in increased basal Pi transport. Ischemia caused similar decline in Pi transport in BBM from LPD and/or T3 animals. However, recovery in these animals was faster than the normal Pi diet fed (NPD) animals. The study suggests a change in the intrinsic properties of the Na-Pi transporter in rat kidneys due to ischemia. The study also indicates that treatment with T3 and feeding LPD prior to ischemia caused faster recovery of phosphate uptake due to ischemia-reperfusion injury.     

Effect of a Low-Protein Diet Supplemented with Ketoacids on Skeletal Muscle Atrophy and Autophagy in Rats with Type 2 Diabetic Nephropathy

A low-protein diet supplemented with ketoacids maintains nutritional status in patients with diabetic nephropathy. The activation of autophagy has been shown in the skeletal muscle of diabetic and uremic rats. This study aimed to determine whether a low-protein diet supplemented with ketoacids improves muscle atrophy and decreases the increased autophagy observed in rats with type 2 diabetic nephropathy. In this study, 24-week-old Goto-Kakizaki male rats were randomly divided into groups that received either a normal protein diet (NPD group), a low-protein diet (LPD group) or a low-protein diet supplemented with ketoacids (LPD+KA group) for 24 weeks. Age- and weight-matched Wistar rats served as control animals and received a normal protein diet (control group). We found that protein restriction attenuated proteinuria and decreased blood urea nitrogen and serum creatinine levels. Compared with the NPD and LPD groups, the LPD+KA group showed a delay in body weight loss, an attenuation in soleus muscle mass loss and a decrease of the mean cross-sectional area of soleus muscle fibers. The mRNA and protein expression of autophagy-related genes, such as Beclin-1, LC3B, Bnip3, p62 and Cathepsin L, were increased in the soleus muscle of GK rats fed with NPD compared to Wistar rats. Importantly, LPD resulted in a slight reduction in the expression of autophagy-related genes; however, these differences were not statistically significant. In addition, LPD+KA abolished the upregulation of autophagy-related gene expression. Furthermore, the activation of autophagy in the NPD and LPD groups was confirmed by the appearance of autophagosomes or autolysosomes using electron microscopy, when compared with the Control and LPD+KA groups. Our results showed that LPD+KA abolished the activation of autophagy in skeletal muscle and decreased muscle loss in rats with type 2 diabetic nephropathy.     

Maternal periconceptional and gestational low protein diet affects mouse offspring growth, cardiovascular and adipose phenotype at 1 year of age

Human and animal studies have revealed a strong association between periconceptional environmental factors, such as poor maternal diet, and an increased propensity for cardiovascular and metabolic disease in adult offspring. Previously, we reported cardiovascular and physiological effects of maternal low protein diet (LPD) fed during discrete periods of periconceptional development on 6-month-old mouse offspring. Here, we extend the analysis in 1 year aging offspring, evaluating mechanisms regulating growth and adiposity. Isocaloric LPD (9% casein) or normal protein diet (18% casein; NPD) was fed to female MF-1 mice either exclusively during oocyte maturation (for 3.5 days prior to mating; Egg-LPD, Egg-NPD, respectively), throughout gestation (LPD, NPD) or exclusively during preimplantation development (for 3.5 days post mating; Emb-LPD). LPD and Emb-LPD female offspring were significantly lighter and heavier than NPD females respectively for up to 52 weeks. Egg-LPD, LPD and Emb-LPD offspring displayed significantly elevated systolic blood pressure at 52 weeks compared to respective controls (Egg-NPD, NPD). LPD females had significantly reduced inguinal and retroperitoneal fat pad: body weight ratios compared to NPD females. Expression of the insulin receptor (Insr) and insulin-like growth factor I receptor (Igf1r) in retroperitoneal fat was significantly elevated in Emb-LPD females (P<0.05), whilst Emb-LPD males displayed significantly decreased expression of the mitochondrial uncoupling protein 1 (Ucp1) gene compared to NPD offspring. LPD females displayed significantly increased expression of Ucp1 in interscapular brown adipose tissue when compared to NPD offspring. Our results demonstrate that aging offspring body weight, cardiovascular and adiposity homeostasis can be programmed by maternal periconceptional nutrition. These adverse outcomes further exemplify the criticality of dietary behaviour around the time of conception on long-term offspring health.     

Effect of phosphate deprivation on enzymes of the cyclic adenosine monophosphate metabolism in rat proximal convoluted and proximal straight tubules.

Phosphate deprivation causes a resistance to the phosphaturic effect of parathyroid hormone (PTH). The present study determined whether acute phosphate deprivation alters basal or stimulated activities of key enzymes of the cyclic adenosine monophosphate (cAMP) metabolism in microdissected proximal convoluted and proximal straight tubules, since blunted cAMP levels in these proximal subsegments might account for refractoriness to the effect of PTH on phosphate reabsorption in the proximal convoluted and proximal straight tubule segments. In the proximal convoluted tubules of rats fed a normal-phosphate diet (NPD), PTH increased the adenylate cyclase activity by tenfold. In the proximal convoluted tubule of rats fed a low-phosphate diet (LPD), PTH also increased the adenylate cyclase activity by tenfold. In addition, forskolin increased the adenylate cyclase activity to levels similar to PTH in the proximal convoluted tubule of rats fed NPD or LPD. In the proximal straight tubule of rats fed NPD, PTH resulted in an approximately fivefold increase in adenylate cyclase activity. In the proximal straight tubule of rats fed LPD, PTH resulted in a fourfold increase in adenylate cyclase activity. The forskolin-stimulated adenylate cyclase activity was markedly decreased (46%) in the proximal straight tubule of phosphate-deprived rats. The cAMP-phosphodiesterase activity in the proximal convoluted tubule was significantly increased by 26% in phosphate-deprived rats. The cAMP-phosphodiesterase activities in the proximal straight tubules from rats fed NPD or LPD were similar. We conclude that distinct differences in key enzymes of cAMP metabolism exist in the proximal convoluted and proximal straight tubule subsegments. Further, phosphate deprivation affects the cAMP-phosphodiesterase and adenylate cyclase activities differently in these nephron subsegments.(ABSTRACT TRUNCATED AT 250 WORDS)     

Renal tubular sites of increased phosphate transport and NaPi-2 expression in the juvenile rat

To determine the tubular sites and mechanisms involved in enhanced renal phosphate (P(i)) reabsorption seen in the juvenile animal, renal micropuncture experiments were performed in acutely thyroparathyroidectomized adult (>14 wk old) and juvenile (4 wk old) male Wistar rats fed either a normal P(i) diet (NPD, 0.6% P(i)) or low P(i) diet (0.07% P(i)) for 2 days, in the presence and absence of parathyroid hormone (PTH). P(i) reabsorption was greater in proximal convoluted (PCT) and straight tubules (PST) of the juvenile compared with adult rats fed NPD, whether or not PTH was present. These findings were consistent with a greater P(i) uptake in brush-border membrane (BBM) vesicles from both superficial (SC) and outer juxtamedullary (JMC) cortices of juvenile animals. Western blot analysis revealed a 2- and 1.8-fold higher amount of NaPi-2 protein in the SC and JMC, respectively, in juvenile rats. Immunofluorescence microscopy also indicated that NaPi-2 protein expression was present in the proximal tubule (PT) BBM to a greater extent in juvenile rats. Dietary P(i) restriction in juvenile rats resulted in a significant increase in P(i) reabsorption in the PCT and PST segments. NaPi-2 expression in the PT BBM was also increased, as was the expression of intracellular NaPi-2 protein. These studies indicate that P(i) reabsorption in both the PCT and PST segments of the renal tubule contributes to the attenuated response to PTH in the normal juvenile animal. In addition, dietary P(i) restriction in the juvenile rat upregulates BBM NaPi-2 expression, which is associated with a further increase in proximal tubular P(i) reabsorption.     

Female rats are protected against the fructose induced mortality of copper deficiency

Experiments were conducted in copper deficient male and female rats fed diets containing fructose or starch in order to determine whether the same type of interaction between copper status and dietary carbohydrate found in male rats also occurs in the female rat. Mortality occurred only in the male rats fed the fructose diet deficient in copper with 40% of the animals dying during the 8 week study. Only anemia, hypercholesterolemia, increased BUN, heart hypertrophy and reduced body weight were observed in these animals which could be related to their mortality. Despite the increased mortality, plasma ceruloplasmin, erythrocyte SOD and hepatic copper concentrations were reduced to a similar extent in all rats regardless of the sex of the animals or of the type of dietary carbohydrate fed. The results of the present study indicate that although direct measurements of copper status of female rats fed fructose diet deficient in copper are similar to their male counterpart, they are apparently protected from the lethal consequences of the deficiency.     

Function specific supersensitivity of m-chlorophenyl piperazine-induced serotonergic neurotransmission in female compared to male rats

Administration of various doses of m-chlorophenylpiperazine (m-CPP), a 5-hydroxytryptamine (5-HT) agonist, to rats increased plasma level sof corticosterone and decreased locomotor activity in a dose dependent manner. The increases of plasma corticosterone but not the decreases of locomotor activity were greater in female than male rats. Hypophagic effects of m-CPP not different in freely feeding male and female rats were greater in females when food deprived animals used. The findings along with our previous report show a functional supersensitivity of 5-HT neurotransmission involved in the regulation of hypothalamo-pituitary adrenocortical axis and appetite supression in female sex, and suggest a possible basis for the greater occurence of depression and anorexia in women than men.     

Moderate zinc deficiency negatively affects biomechanical properties of rat tibiae independently of body composition

To guide development of novel nutritional strategies aimed at reducing the incidence of stress fractures, we observed the effects of manipulating dietary zinc (Zn) content on bone integrity in Sprague–Dawley rats fed either a severely Zn-deficient (ZnD; 1 ppm), a moderately Zn-deficient (MZnD; 5 ppm) or a Zn-adequate (ZnAD; 30 ppm) diet for 6 weeks. At the completion of the diet period, body composition, bone mineral content (BMC), bone area (BA) and bone mineral density (BMD) were determined in vivo by using dual-energy X-ray absorptiometry. Following euthanasia, long bones were collected for determination of Zn content and biomechanical strength testing. Despite significant positive correlations between dietary Zn and both body weight (BW) and bone Zn content for the entire cohort (r=.77 and r=.83, respectively), rats fed MZnD or ZnAD diets did not differ in feed intakes, body composition, BMC, BA, BMD or BW. Tibial bones, but not femur bones, appear to be more responsive to dietary Zn manipulation, as all bone biomechanical strength indices in the ZnAD-fed rats were significantly greater than in rats fed the ZnD diets. Rats fed either MZnD or ZnAD diets had stronger tibiae (129% increase in maximum load and stress at maximum load, P<.01) compared with those fed ZnD diets. The load at breakage for the tibial bones of rats fed MZnD diets was not different from the ZnD rats, but lower (P<.05) than that of the ZnAD rats. These results suggest that since feed intakes, body composition, BMC, BA, BMD and BW were not significantly different between the MZnD- and ZnAD-fed animals, the reduced bone integrity observed in the MZnD-fed rats resulted from dietary Zn inadequacy, and not as a result of the reduced growth that is typically associated with Zn deficiency.     

Effect of a low-protein diet supplemented with keto-acids on autophagy and inflammation in 5/6 nephrectomized rats

Ketoacids (KA) are known to preserve muscle mass among patients with chronic kidney disease (CKD) on a low-protein diet (LPD). The present study was to compare the effects of KA supplemented diet therapy in autophagy and inflammation in CKD rats'' skeletal muscle. Rats with 5/6 nephrectomy were randomly divided into three groups and fed with either 11 g/kg/day protein [normal-protein diet (NPD)], 3 g/kg/day protein (LPD) or 3 g/kg/day protein which including 5% protein plus 1% KA (LPD + KA) for 24 weeks. Sham-operated rats with NPD intake were used as control. LPD could improve body weight, gastrocnemius muscle mass, as well as gastrocnemius muscle cross-sectional area, with the effect being more obvious in the LPD + KA group. The autophagy marker LC3 (microtubule-associated protein 1 light chain 3), p62, Parkin and PTEN induced putative kinase 1 (PINK1) were significantly attenuate in LPD + KA group than LPD group. LPD + KA group had the lower total mtDNA (mitochondiral DNA) and cytosol mtDNA, NACHT-PYD-containing protein 3 (NALP3) inflammasome than LPD group, but its reactive oxygen species (ROS), caspase-1 and apoptosis-associated speck-like protein containing a CARD (ASC) level was higher. Immunoblotting showed IL-1β (interleukin-1-beta) was lower in LPD and LPD + KA group than the NPD group, but IL-18 showed no significant difference among control and CKD group; toll-like receptor signalling-dependent IL-6 was higher in LPD + KA group than LPD group, but tumor necrosis factor-α (TNF-α) was not significantly changed between LPD + KA and LPD group. Systematic changes of the four cytokines were different from that of the tissue. Although LPD + KA could further ameliorate-activated autophagy than LPD, its effect on the activated inflammation state in CKD was not distinctly. Further study is still required to explore the method of ameliorating inflammation to provide new therapeutic approaches for CKD protein energy wasting (PEW).     

15N-Harnstoffumsatz bei Schafen nach Verabreichung in gelöster Form

Two slaughter experiments were carried out to determine whether the protein content of the diet has an influence upon the efficiency of utilization of ME in fast growing chickens. A normal‐protein diet (NPD, 204 g CP/kg DM; 14.7 MJ ME/kg DM) based on soybean meal as the sole source of protein was given at four different levels of intake (ad libitum or restricted at about 90, 65 and 40% ad lib) to 10‐d‐old animals for 2 weeks. In a parallel experiment the chickens were fed ad libitum a low protein diet (LPD, 66 g CP/kg DM; 15.0 MJ ME/kg DM) based on soybean meal. The intake of metabolizable energy ranged from 1675 to 777 and 1770 to 832 kJ/kgW^0.75 per day for NPD and LPD treatments, respectively. Mean values of energy retention, gross efficiency of energy utilization and energy retained as protein were significantly (P<. 05) lower and heat production (expressed as both kJ/kgW^0.75 per day and kJ/kg body protein content^0.75 per day) was significantly higher (P < .05) for the chickens fed on LPD. These findings support the concept of dietary‐induced thermogenesis in response to reductions in dietary protein concentration. It is concluded that the increased heat production found in the birds fed on the low‐protein diet can be explained by both an increase in energy requirements for maintenance (ME_m) and a sharp decrease in the efficiency of utilization of ME for growth (k₈).     

Response of animals to dietary gramine. II. effects of feeding high‐gramine yellow lupin seeds on reproductive performance of rats and on selected hematological and biochemical parameters in offspring

Two groups of 26 male and 26 female rats at the initial age 30 ± 2 days were fed during 31 weeks on diets containing 20 percent of yellow lupin seeds having low (LG) or high (HG) gramine content. The animals were mated twice within nutritional groups, 1 male: 1 female, and their main reproductive parameters were recorded. In both reproductive cycles body weight of females at mating, after parturition and after 21‐days lactation was lower in HG than in LG group. Fertility rate and body weight of neonates were not affected by the diet while number of neonates per litter tended to be lower by 0.7 and 0.8 pups in HG than in LG group. Body weight of weaners was also substantially smaller in dams fed on HG than LG diet. Relative weight of spleen but not of liver, kidney and heart was significantly greater in HG females. Four weeks old males and females issued from the first litters born to LG and HG animals (ten males and ten females per treatment) were fed individually on respective diets during 3 weeks. Feed intake and growth rate did not differ between the treatments. In males relative weight of liver and testicles was greater, while hematocrit and red blood count were lower in HG than in LG group. In females organ weights did not differ. Activity of liver enzymes determined in males was not affected by the diet. It may be concluded that high‐gramine lupin affects negatively lactational performance, probably via lower feed intake, but it does not induce apparent teratogenic effects in the progeny.     

Effects of konjac flour inclusion in gestation diets on the nutrient digestibility,lactation feed intake and reproductive performance of sows

This study was conducted to investigate the effects of konjac flour (KF) inclusion in gestation diets of sows on nutrients digestibility, lactation feed intake, reproductive performance of sows and preweaning performance of piglets. Two isoenergetic and isonitrogenous gestation diets were formulated: a control diet and a 2.1% KF-supplemented diet (KF diet). Both diets had the same NDF and insoluble fiber (ISF) levels, but the KF diet had higher soluble fiber (SF) level. The day after breeding, 96 multiparous sows were assigned to the two dietary treatments. Restrict-fed during gestation, in contrast, all sows were offered the same lactation diet ad libitum. Response criteria included sow BW, backfat depth, lactation feed intake, weaning-to-estrus interval, litter size and piglet’s weight at parturition and day 21 of lactation. On day 60 of gestation, 20 sows were used to measure nutrient digestibility. Results showed that the digestibility of dry matter, gross energy, crude fiber and ADF were not affected by the dietary treatments. The inclusion of KF in gestation diets increased NDF digestibility (P<0.05) and tended to increase the digestibility of CP (P=0.05) compared with the control diet group. In addition, dietary treatment during gestation did not affect litter size, BW and backfat gain during gestation, lactation weight, backfat loss or weaning-to-estrus interval of sows. However, sows fed the KF diet consumed more (P<0.05) lactation diet per day than sows in the control group. Accordingly, sows fed the KF diet showed greater average piglet weights on day 21 of lactation (P=0.09), and the litter weight of sows fed the KF diet on day 21 of lactation increased by 3.95 kg compared with sows fed the control diet (not significant). In conclusion, the inclusion of KF in gestation diets increased lactation feed intake of sows and tended to improve litter performance.     

Perinatal salt restriction: a new pathway to programming adiposity indices in adult female Wistar rats

Low birth weight has been associated with increased obesity in adulthood. It has been shown that dietary salt restriction during intrauterine life induces low birth weight and insulin resistance in adult Wistar rats. The present study had a two-fold objective: to evaluate the effects that low salt intake during pregnancy and lactation has on the amount and distribution of adipose tissue; and to determine whether the phenotypic changes in fat mass in this model are associated with alterations in the activity of the renin-angiotensin system. Maternal salt restriction was found to reduce birth weight in male and female offspring. In adulthood, the female offspring of dams fed the low-salt diet presented higher adiposity indices than those seen in the offspring of dams fed a normal-salt diet. This was attributed to the fact that adipose tissue mass (retroperitoneal but not gonadal, mesenteric or inguinal) was greater in those rats than in the offspring of dams fed a normal diet. The adult offspring of dams fed the low-salt diet, compared to those dams fed a normal-salt diet, presented the following: plasma leptin levels higher in males and lower in females; plasma renin activity higher in males but not in females; and no differences in body weight, mean arterial blood pressure or serum angiotensin-converting enzyme activity. Therefore, low salt intake during pregnancy might lead to the programming of obesity in adult female offspring.     

Insulin secretion and GLUT-2 expression in undernourished neonate rats

In previous studies, we verified increased insulin sensitivity in adult male offspring of lactating rats readjusting to lack of insulin secretion reduction brought about by protein restriction during lactation. The present study aims to evaluate the effects of maternal protein undernutrition during lactation on glucose-induced insulin secretion and GLUT-2 expression in beta-cells of neonate male and female rats. Lactating Wistar rats were given a protein-free diet during the first 10 days and a normal diet (22% of protein) until weaning. The neonates were separated at birth by sex and diet and studied at 4, 8 and 21 days of lactation. Glucose-induced insulin secretion by pancreatic islets was analyzed by radioimmunoassay and GLUT-2 expression in beta-cells by Western blot. Glucose-induced insulin secretion of the undernourished groups was higher than in the control groups except among females. When comparing the male and female groups and the control and undernourished groups, female neonates showed significantly greater insulin secretion than the male group. Also it was noted that undernutrition induced greater GLUT-2 expression. For instance, comparing the undernourished male and female neonates there was an increase in female GLUT-2 expression on day 4. On the other hand, in undernourished male neonates a GLUT-2 expression increased later in lactation. In conclusion, during a short term, maternal undernutrition induces an increase of the glucose-induced insulin secretion only in male neonates and is associated with an increase in GLUT-2 expression in the beta-cell.     

Dynamic changes in morphology,gene expression and microbiome in the jejunum of compensatory‐growth rats induced by protein restriction

We previously reported that protein‐restricted rats experienced compensatory growth when they were switched to a normal protein diet (NPD). This study aimed to investigate the changes in gene expression and microbiome in the jejunum of compensatory‐growth rats. Weaned Sprague‐Dawley rats were assigned to an N group, an LN group and an L group. The rats in the L and N groups were fed a low protein diet (LPD) and the NPD respectively. The rats in the LN group were fed with the LPD for 2 weeks, followed by the NPD. The experiment lasted 70 days, and the rats were sacrificed for sampling on days 14, 28 and 70 to determine the jejunal morphology, microbiome and gene expression related to digestive, absorptive and barrier function. The results showed that, although rats in the LN group had temporarily impaired morphology and gene expression in the jejunum on day 14 in response to the LPD, they had improved jejunal morphology and gene expression related to jejunal function on day 28 compared to rats in the N group. This improvement might promote compensatory growth of rats. However, lower expression of genes related to nutrient absorption and undifferentiated villous height (VH) were observed in the jejunum of rats in the LN group on day 70. In contrast, rats in the L group had lower VH on day 28 and day 70, while the expression of absorptive genes increased on day 28 compared to rats in the N group. Additionally, dramatic microbial changes in the jejunum of compensatory‐growth rats were observed, principally for Lactobacillus, Streptococcus, Corynebacterium and Staphylococcus. Moreover, the abundance of Lactobacillus, Streptococcus, Corynebacterium and Staphylococcus significantly correlated with gene expression in the jejunum as revealed by the correlation analysis.     

Effect of deoxynivalenol (vomitoxin) on fertility, pregnancy, and postnatal development of Sprague-Dawley rats.

A diet containing 20 ppm (micrograms/g) of purified deoxynivalenol (DON) was fed to male and female Sprague-Dawley rats for 60 and 15 days, respectively, before breeding. Rats consuming feed amended with DON throughout pregnancy and lactation showed no clinical signs of toxicity, nor did the control or pair-fed control groups. Male rats in the DON treatment group showed no feed refusal but were less efficient than males in control groups in converting feed into body mass. Feed refusal in female rats varied with stage of pregnancy. Before breeding, overall feed consumption was similar in all groups, but in the DON treatment group there was significant feed refusal for the first 2 days. Feed conversion efficiency was reduced in the DON treatment group. Pregnant and lactating rats fed DON-treated feed ate 6% less than did control rats fed solvent-treated feed. Although pair-fed control rats ate 14 to 21% less than rats in the DON treatment group, their body weights were greater than those of the DON group rats throughout most of the feeding trials, indicating that DON has a toxic effect. Only 50% of the matings between DON group rats resulted in pregnancy, compared with 80% in the control groups. There were no differences detected among groups in ratio of male to female pups, survival rate, or average litter number and weight. Pup weight gains in all groups were comparable through postnatal day 14.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of deoxynivalenol (vomitoxin) on fertility, pregnancy, and postnatal development of Sprague-Dawley rats

A diet containing 20 ppm (micrograms/g) of purified deoxynivalenol (DON) was fed to male and female Sprague-Dawley rats for 60 and 15 days, respectively, before breeding. Rats consuming feed amended with DON throughout pregnancy and lactation showed no clinical signs of toxicity, nor did the control or pair-fed control groups. Male rats in the DON treatment group showed no feed refusal but were less efficient than males in control groups in converting feed into body mass. Feed refusal in female rats varied with stage of pregnancy. Before breeding, overall feed consumption was similar in all groups, but in the DON treatment group there was significant feed refusal for the first 2 days. Feed conversion efficiency was reduced in the DON treatment group. Pregnant and lactating rats fed DON-treated feed ate 6% less than did control rats fed solvent-treated feed. Although pair-fed control rats ate 14 to 21% less than rats in the DON treatment group, their body weights were greater than those of the DON group rats throughout most of the feeding trials, indicating that DON has a toxic effect. Only 50% of the matings between DON group rats resulted in pregnancy, compared with 80% in the control groups. There were no differences detected among groups in ratio of male to female pups, survival rate, or average litter number and weight. Pup weight gains in all groups were comparable through postnatal day 14.(ABSTRACT TRUNCATED AT 250 WORDS)     

Prevention of diet-induced obesity and impaired glucose tolerance in rats following administration of leptin to their mothers

Absence of leptin is known to disrupt the development of energy balance regulatory mechanisms. We investigated whether administration of leptin to normally nourished rats affects energy balance in their offspring. Leptin (2 mg.kg(-1).day(-1)) was administered from day 14 of pregnancy and throughout lactation. Male and female offspring were fed either on chow or on high-fat diets that elicited similar levels of obesity in the sexes from 6 wk to 15 mo of age. Treatment of the dams with leptin prevented diet-induced increases in the rate of weight gain, retroperitoneal fat pad weight, area under the intraperitoneal glucose tolerance curve, and fasting plasma insulin concentration in female offspring. In the male offspring, the diet-induced increase in weight gain was prevented and increased fat pad weight was reduced. Energy intake per rat was higher in response to the obesogenic diet in male offspring of saline-treated but not leptin-treated dams. A similar trend was seen in 3-mo-old female offspring. Energy expenditure at 3 mo of age was higher for a given body weight in female offspring of leptin-treated compared with saline-treated dams when these animals were fed on the obesogenic diet. A similar trend was seen for male rats fed on the obesogenic diet. Thus leptin levels during pregnancy and lactation can affect the development of energy balance regulatory systems in their offspring.     

Hepatic fructose-metabolizing enzymes and related metabolites: role of dietary copper and gender

The purpose of this study was to further examine the hypothesis that variations in hepatic fructose-metabolizing enzymes between males and females might account for the differences in the severity of copper (Cu) deficiency observed in fructose-fed male rats. Weanling rats of both sexes were fed high-fructose diets either adequate or deficient in copper for 45 days. Cu deficiency decreased sorbitol dehydrogenase activity and dihydroxyacetone phosphate levels and increased glyceraldehyde levels in both sexes. Gender effects were expressed by higher activities of glycerol 3-phosphate dehydrogenase and aldehyde dehydrogenase in male than in female rats and higher levels of dihydroxyacetone phosphate and fructose 1,6-diphosphate (F1,6DP) in female than in male rats. The interactions between dietary Cu and gender were as follows: alcohol dehydrogenase activities were higher in female rats and were further increased by Cu deficiency in both sexes; aldehyde dehydrogenase activities were decreased by Cu deficiency only in male rats; sorbitol levels were higher in male rats and were further increased by Cu deficiency in male rats; fructose 1-phosphate (F1P) levels were increased by Cu deficiency in both sexes, but to a greater extent in male rats; glyceraldehyde 3-phosphate levels were higher in female rats, but were decreased by Cu deficiency in female and increased in male rats. Though most of the examined hepatic fructose-metabolizing enzymes and metabolites showed great differences between rats fed diets either adequate or deficient in Cu, it is the activity of fructokinase and aldolase-B, and the concentrations of their common metabolites, F1P and notably F1,6DP, that could be in part responsible for differences in the severity of pathologies associated with Cu deficiency observed between female and male rats.