Effect of food restriction on serotonin metabolism in rat brain

The brain concentration of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) increased in rats maintained on restricted volume of low-protein or normal-protein diet, whereas these two agents decreased in rats fed low-protein diet ad libitum. In these two food-restricted groups brain 5-HT and 5-HIAA concentrations were not correlated with brain tryptophan hydroxylase activity, but the concentrations correlated closely with cerebral tryptophan concentrations. The cerebral tryptophan concentration in the two food-restricted groups was not consistent with the total or free tryptophan concentration in plasma. In these restricted rats cerebral tryptophan concentration was elevated, and, unlike the plasma tryptophan, it showed no diurnal variation. These results suggested that tryptophan uptake into the brain from plasma was enhanced by limiting food volume intake. Tryptophan uptake was increased by glucagon injection without changing the plasma tryptophan level, but injection of hydrocortisone or insulin had little or no effect on tryptophan concentration in either the plasma or brain.d-Glucose injection elevated plasma tryptophan concentration but decreased brain tryptophan concentration.     

Effect of maternal feed restriction during pregnancy on glucose tolerance in the adult guinea pig

Maternal nutrient restriction and impaired fetal growth are associated with postnatal insulin resistance, hyperinsulinemia, and glucose intolerance in humans but not consistently in other species, such as the rat or sheep. We therefore determined the effect of mild (85% ad libitum intake/kg body wt) or moderate (70% ad libitum intake/kg body wt) maternal feed restriction throughout pregnancy on glucose and insulin responses to an intravenous glucose tolerance test (IVGTT) in the young adult guinea pig. Maternal feed restriction reduced birth weight (mild and moderate: both P < 0.02) in male offspring. Moderate restriction increased plasma glucose area under the curve (P < 0.04) and decreased the glucose tolerance index (K(G)) (P < 0.02) during the IVGTT in male offspring compared with those of mildly restricted but not of ad libitum-fed mothers. Moderate restriction increased fasting plasma insulin (P < 0.04, adjusted for litter size) and the insulin response to IVGTT (P < 0.001), and both moderate and mild restriction increased the insulin-to-glucose ratio during the IVGTT (P < 0.003 and P < 0.02) in male offspring. When offspring were classed into tertiles according to birth weight, glucose tolerance was not altered, but fasting insulin concentrations were increased in low compared with medium birth weight males (P < 0.03). The insulin-to-glucose ratio throughout the IVGTT was increased in low compared with medium (P < 0.01) or high (P < 0.05) birth weight males. Thus maternal feed restriction in the guinea pig restricts fetal growth and causes hyperinsulinemia in young adult male offspring, suggestive of insulin resistance. These findings suggest that mild to moderate prenatal perturbation programs postnatal glucose homeostasis adversely in the guinea pig, as in the human.     

Effects of exercise and food restriction on rat skeletal muscles.

Studies were undertaken to compare the effects of exercise and food restriction on body weight (BW), muscle weight (MW), muscle fiber size, and proportion of muscle fiber types. 20 male Fischer 344 rats were randomly assigned to four equal groups: ad libitum-fed control (AC), ad libitum-fed exercise (AE), food restricted control (RC) and food restricted exercise (RE). From 6 weeks of age, RC and RE rats received 60% of the daily food intake of AC and AE rats, respectively. At 7 months of age, AE and RE rats began 40-50 min of daily treadmill exercise. Running speed increased from 1.2 to 1.6 miles/hour and the grade increased to 15% during the first 2 weeks of training. After 10 weeks of training, rats were weighed, sacrificed, and the soleus (SOL), plantaris (PLN) and extensor digitorum longus (EDL) muscles were removed at in situ rest length, weighed, and quick-frozen. Standard histochemical assays were performed, and muscle fiber cross-sectional area was determined planimetrically. Training had little effect on MW or BW, but food restriction greatly reduced BW. This resulted in greater MW/BW ratio in RC and RE than AC and AE rats, respectively. Exercise also increased SOL muscle fiber area in ad libitum-fed but not food restricted rats resulting in smaller fibers in SOL of RE than AE. No changes in percentage of SOL fiber types occurred with food restriction or exercise. In PLN, the percentage of fast-twitch oxidative fibers of AE and RE was greater than in AC and RC, but there was no effect of food restriction or exercise on fiber area.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of food restriction on the insulin signalling pathway in rat skeletal muscle and adipose tissue

We tried to elucidate the effects of a brief and severe model of food restriction on insulin sensitivity in female rats, focusing on key proteins involved in the insulin signalling pathway in skeletal muscle and adipose tissue after 5, 10 and 15 days of food restriction. Using euglycemic clamp, we detected that food-restricted rats are significantly less sensitive to insulin action than control rats. However, the time of restriction promotes a progressive increase on insulin sensitivity. The analysis of the insulin signalling pathway showed a tissue-specific regulation of several proteins involved in insulin signalling. In skeletal muscle, insulin receptor substrate 1 and Glut4 are up-regulated at the end of the food restriction period, just the opposite of what we found in adipose tissue. In conclusion, a 50% reduction of food intake modulates insulin sensitivity through a tissue-specific regulation of the insulin signalling pathway in the main target tissues for this hormone.     

Hormonal basis of hysterectomy-induced maternal behavior during pregnancy in the rat.

Hysterectomy during the last half of pregnancy (i.e., Day 10–19) induces a rapid onset of maternal behavior; ovariectomy in addition to hysterectomy, prevents this effect. Estradiol and progesterone were tested for their ability to restore short-latency maternal behavior in hysterectomized-ovariectomized (HO) females operated on the 10th, 13th, 16th and 19th days of pregnancy. A single injection of either 20 μg/kg or 100 μg/kg estradiol benzoate (EB) immediately following HO either alone or followed by 0.5 mg progesterone (P) 44 hr later restored short-latency maternal behavior similar to that observed following hysterectomy only. The lower dose of EB was found to be equally effective at all stages of pregnancy and P was unnecessary to induce maternal behavior. The effectiveness of EB in inducing maternal behavior was discussed in relation to the hormonal changes which follow hysterectomy during pregnancy and to those which are associated with the normal onset of maternal behavior around parturition.     

Effects of maternal food restriction during lactation on craniofacial growth in weanling rats

Adult Holtzman rats were submitted during suckling period to a food restriction with or without protein or carbohydrate restoration. Twenty-one-day-old weanling pups were compared with controls of 9, 13, 17, and 21 days of age. Lateral craniofacial roentgenographies were taken. The length in midsagittal plane of each bone and its angle with respect to the vestibular line were measured in males. In females, the brain and the left masseter muscle were weighed, and the muscle/brain ratios (neuromuscular index) were calculated. Food restriction altered skull size and shape. Size changes were due to arrested lengths in all studied skull bones. Shape variation was evident by orthocephalization changes, reflected in angulation changes of bones belonging to the frontoethmofacial (frontal, nasal, and maxillary bones) and to the occipitointerparietal (interparietal bone) complexes. Partial restorations by both protein or carbohydrate supplementation were found. Nutritional stresses during lactation affected orthocephalization through an altered growth ratio between two soft tissues functionally associated to the craniofacial complex: brain and masticatory muscles.     

Cleft palate following prenatal food restriction in mice: association with elevated maternal corticosteroids.

Following food restriction of pregnant CD-1 mice, the maternal serum corticosteroid levels and incidence of skeletal and visceral abnormalities of the progeny were determined. Dams from the groups receiving restricted food on gestation days 6 to 15 had increased resorptions, and the progeny had delayed ossification of the skeleton with cleft palate accompanied by delayed ossification of the presphenoid bone. The incidence and intensity of these changes was correlated with the level of food restriction. The incidence of cleft palate for progeny from dams receiving 4.0 to 2.5 g of feed per day ranged from 6.3% to 100.0%, respectively. Serum corticosteroid levels of pregnant control and food restricted dams were similar on gestation day 10, but the levels of food restricted dams were 6 to 10 times greater than controls on gestation day 15. Thus cleft palate, delayed skeletal ossification, and increased resorptions are predictably produced by food restriction of CD-1 mice and were highly correlated with the elevated endogenous serum corticosteroid levels.     

Effect of pregnancy on joint contracture in the rat knee.

As there is evidence that ligamentous laxity is affected by the female hormones, we hypothesized that hormonal changes occurring during pregnancy could have a therapeutic role in preventing the development of a joint contracture. Knee joint contractures were created in pregnant and nonpregnant rats. After 2 wk of immobilization, the degree of contracture was measured with structural properties of the medial collateral and anterior cruciate ligaments and the pubic symphysis. Although not statistically significant, there was a general trend toward reduced contracture in pregnant compared with nonpregnant rats. Cutting the posterior capsule significantly decreased contracture for both the pregnant and nonpregnant groups, confirming the contribution of capsular structures to contracture. Ultimate loads of the medial collateral and anterior cruciate ligaments significantly decreased after immobilization compared with control, but there was no significant effect due to pregnancy. Stiffness and ultimate load of the pubic symphysis were not significantly different between pregnant and nonpregnant groups. The trend toward reduced contracture with pregnancy points toward a possible therapeutic role for female hormones in the prevention of postoperative and/or posttraumatic joint contracture.     

Effect of food restriction on cold adaptability of rats

To determine the role of the nutritional state in nonshivering thermogenesis during cold adaptation, cold adaptability was compared between cold-adapted (5 degrees C for 4-5 weeks) rats fed ad libitum and cold-adapted rats pair fed with warm controls having the same food intake. Cold-adapted pair-fed rats suffered a significant loss in body weight during cold exposure. However, brown adipose tissue (BAT) in both cold-adapted ad libitum fed and cold-adapted pair-fed rats was enlarged to the same extent as compared with that in control rats. Fat-free dry matter in BAT also increased in cold-adapted ad libitum fed and cold-adapted pair-fed rats to the same extent. Cold tolerance as assessed by the change in the colonic temperature at -5 degrees C was improved relative to control rats and was the same for cold-adapted ad libitum fed and cold-adapted pair-fed rats. Nonshivering thermogenesis as estimated by the noradrenaline-induced increase in oxygen consumption was significantly greater in the cold-exposed rats and there was no significant difference between cold-adapted ad libitum fed and cold-adapted pair-fed rats. These results suggest that an improved cold tolerance by means of nonshivering thermogenesis in brown adipose tissue is closely related to the low temperature itself but not the increased food intake which occurred in the cold.     

The impact of maternal protein restriction during rat pregnancy upon renal expression of angiotensin receptors and vasopressin-related aquaporins

Background  

Maternal protein restriction during rat pregnancy is known to impact upon fetal development, growth and risk of disease in later life. It is of interest to understand how protein undernutrition influences the normal maternal adaptation to pregnancy. Here we investigated the mechanisms regulating renal haemodynamics and plasma volume during pregnancy, in the context of both normal and reduced plasma volume expansion. The study focused on expression of renal angiotensin receptors (ATR) and vasopressin-related aquaporins (AQP), hypothesising that an alteration in the balance of these proteins would be associated with pregnancy per se and with compromised plasma volume expansion in rats fed a low-protein diet.     

Effect of maternal nutrient restriction in sheep on the development of fetal skeletal muscle

The effect of maternal nutrient restriction on mTOR (mammalian target of rapamyosin) signaling and the ubiquitin system as well as their possible relation to growth of fetal muscle was determined. Ewes were fed to 50% (nutrient-restricted) or 100% (control-fed) of total digestible nutrients (National Research Council requirement) from Days 28 to 78 of gestation. Ewes were killed at Day 78 of gestation, and the fetal longissimus dorsi muscle was sampled for the measurement of mTOR, ribosomal protein S6, AMP-activated protein kinase (AMPK), calpastatin, and protein ubiquitylation. No difference was observed in the content of mTOR and ribosomal protein S6, but the phosphorylation of mTOR at Ser2448 and ribosomal protein S6 at Ser235/336 were reduced (P <0.05) in muscle from nutrient-restricted fetuses. Because phosphorylation of mTOR and ribosomal protein S6 up-regulates protein translation, these results show that nutrient restriction down-regulates protein synthesis in fetal muscle. No difference in AMPK activity was detected. The lack of difference in calpastatin and ubiquitylized protein content shows that nutrient restriction did not affect degradation of myofibrillar proteins in fetal muscle. Fetuses of nutrient-restricted ewes showed retarded development of muscles and skeleton. Muscle from nutrient-restricted fetuses contained fewer secondary myofibers than muscle from control fetuses, and the average area of fasciculi was smaller (P <0.05). The decreased number of secondary myofibers in nutrient-restricted fetuses may result from the decreased mTOR signaling. Lower activation of mTOR signaling in nutrient-restricted fetuses may reduce the proliferation of myoblasts and, thus, reduce the formation of secondary myofibers. This decrease in secondary myofibers in fetuses may predispose fetuses to metabolic diseases, such as diabetes and obesity, in their postnatal lives.     

Influence of food restriction during gestation on craniofacial growth of the weanling rat

Holtzman rats were subjected to food restriction during gestation or lactation, or both periods (overall stress). At weaning, male pup skulls were measured and female brains and cranial masticatory muscles were weighed and a neuromuscular index was calculated. It was found that gestational protein-calorie malnutrition (PCM) without suckling restoration accounted for about 30% of the growth delay observed under overall stress. That effect disappeared after a normal suckling restoration. Under the same conditions of maternal food restriction in both periods, growth delay in the offspring was greater during lactation than gestation. As in lactation, craniofacial changes during gestational restriction were due to an adjustive response of bone growth to PCM. This response seemed to accrue from an altered relationship between the growth of the brain-less sensitive and highly restorable-and the growth of the masticatory muscles-more sensitive and less restorable. Some degree of delay in orthocephalization would be the skeletal outcome of such adjustive neuromuscular response.     

Long-term effects of maternal magnesium restriction on adiposity and insulin resistance in rat pups

Objective: We investigated the long‐term effects of maternal/postnatal magnesium (Mg) restriction on adiposity, glucose tolerance, and insulin secretion in the offspring and the probable biochemical mechanisms associated with them. Methods and Procedures: Female weanling Wistar/NIN (WNIN) rats received a control diet or 70% Mg‐restricted (MgR) diet for 9 weeks and mated with control males. A third of the restricted dams were shifted to control diet from parturition. Half of the pups born to the remaining restricted dams were weaned on to control diet, while the other half continued on MgR diet. Various parameters were determined in the offspring at 18 months of age. Results: The percentage of body fat increased, lean body mass (LBM) and fat free mass (FFM) decreased in restricted offspring and were irreversible by rehabilitation. While glucose tolerance and insulin resistance (IR) were comparable among groups, glucose‐stimulated insulin secretion and basal glucose uptake by the diaphragm were significantly decreased in restricted offspring and not corrected by rehabilitation. Plasma leptin was lower, and tumor necrosis factor‐α (TNF‐α) was higher in restricted offspring, whereas expression of fatty acid synthase (FAS) and fatty acyl transport protein 1 (FATP 1) was higher in liver and adipose tissue. While changes in FAS and FATP 1 were not correctible by rehabilitation, those in leptin and TNF‐α were corrected by rehabilitation from parturition but not from weaning. Tissue oxidative stress and antioxidant status were comparable among groups. Discussion: Results indicate that maternal and postnatal Mg status is important in the long‐term programming of body adiposity and insulin secretion in rat offspring.     

Effects of the diet consumed during the pregnancy on the lipids content in maternal and fetal rat lungs.

This study was designed to determine if the quantity of lipids in the diet fed to pregnant rats would affect the deposition of fat in the fetal lung. Wistar rats were fed with two different diets during pregnancy: Standard Diet (StD; 4.000 cal/g) and High Fat Carbohydrate Free Diet (HFCFD; 6.000 cal/g). The rats consumed daily the same amount of calories from these different diets. The concentrations of triglycerides (TG), phospholipids (PL), total, esterified and free cholesterol (TC, EC and FC, respectively) were determined in serum and lung from pregnant rats as well as from their 19 day old fetuses. In the serum of rats fed with HFCFD, the cholesterol concentration increased in relation to that of rats fed with StD. In pregnant rat lung, the PL concentrations decreased and the TC, EC and FC concentrations increased with HFCFD in relation to StD. The triglycerides were not modified in any case. The lipidic composition of the sera and fetal lung were not changed by the two diets consumed by pregnant rats. This may be a biological protective mechanism to assure an adequate synthesis of alveolar surfactant.     

Effect of blastocysts on rat ovarian steroidogenesis in early pregnancy.

The biosynthesis of ovarian progesterone and 20alpha-hydroxypregn-4-en-3-one (20alpha-OHP) was studied in rats with pituitaries autotransplanted beneath the kidney capsule (APTr rats) 1 1/2 days after ovulation. Some animals underwent tubal ligation 1-2 weeks prior to mating. Incubated ovarian tissue slices showed an accumulation of progesterone of 64 plus or minus 11 mcg/g tissue, and a progesterone/20alpha-OHP ratio of .32 plus or minus .16. Ovarian tissue from APTr rats with viable blastocysts synthesized considerably more progesterone than tissue from tubal ligated APTr rats. The increased concentrations of progesterone were associated with decreased concentrations of 20alpha-OHP. The accumulation of progesterone in tissue from unmated APTr rats, APTr rats cervically stimulated at proestrus, and similar cervically stimulated rats with traumatized uteri was 42 plus or minus 5, 16 plus or minus 4 and 18 plus or minus 9 net mcg/g tissue, respectively. The progesterone accumulation in tissue from cervically stimulated rats was thus similar to that in tissue from tubal ligated animals. This inhibition by cervical stimulation was overcome by stimuli from the blastocysts. The results suggest that the blastocyst secretes a substance that is more active in promoting progesterone formation than pituitary prolactin.     

Maternal hyperinsulinemia predisposes rat fetuses for hyperinsulinemia, and adult-onset obesity and maternal mild food restriction reverses this phenotype

We have previously shown that artificial rearing of newborn female rat pups on a high-carbohydrate (HC) milk formula resulted in chronic hyperinsulinemia and adult-onset obesity (HC phenotype) and that the maternal HC phenotype was transmitted to their progeny (2-HC rats) because of fetal development in the HC female rat. The aims of this study were to investigate 1) the fetal adaptations that predisposed the progeny for the expression of the HC phenotype in adulthood and 2) whether the transfer of the HC phenotype to the progeny could be reversed by maternal food restriction. Fetal parameters such as plasma insulin and glucose levels, mRNA level of preproinsulin gene, pancreatic insulin content, and islet insulin secretory response in vitro were determined. On gestational day 21, 2-HC fetuses were hyperinsulinemic, had increased insulin content and mRNA level of the preproinsulin gene in their pancreata and demonstrated an altered glucose-stimulated insulin secretory response by isolated islets. Modification of the intrauterine environment in HC female rats was achieved by pair feeding them to the amount of diet consumed by age-matched control rats from the time of their weaning. This mild dietary restriction reversed their HC phenotype and also prevented the development of the HC phenotype in their progeny. These findings show that mal-programming of the progeny of the hyperinsulinemic-obese HC female for the expression of the HC phenotype is initiated in utero and that normalization of the maternal environment in HC female rats by mild food restriction resulted in the normal phenotype in their progeny.     

限食及重喂食对雄性长爪沙鼠生理指标的影响

限食通常会显著影响鼠类的营养及内分泌等生理指标,但限食后重喂食其生理指标是否能得以恢复尚不
清楚。本文采取70% 的限食水平,研究了限食及重喂食对雄性长爪沙鼠生理指标的影响。将雄性长爪沙鼠分为
限食组、重喂食组和对照组。限食组先自由饮食4 周,后70% 限食4 周;重喂食组先70% 限食4 周,后恢复自
由饮食4 周。对照组自由饮食8 周。实验结束时,检测各组肥满度及血清白蛋白和总蛋白含量、血清甲状腺素
T3 和T4 水平、睾酮和皮质醇含量等各项生理指标的变化。研究结果表明,4 周限食显著降低了雄性长爪沙鼠的肥满度和血清甲状腺素T4 含量,显著升高了其血液皮质醇含量;限食后重喂食4 周后可使上述指标恢复或接近正常,但血清白蛋白含量比对照组低,其他指标与对照组无明显差异,长爪沙鼠的一些生理指标在限食重喂食
后能得以恢复,但其内分泌调节可能存在新的变化,值得进一步研究。