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PubMed1999

Attenuation of bleomycin-induced Hprt mutant frequency in female and male rats by calorie restriction.

Calorie restriction modulates spontaneous and chemically induced tumors and increases maximal life span in experimental animals; however, the mechanism by which calorie restriction exerts its ameliorating effects is not fully elucidated, although reduced levels of reactive oxygen species (ROS) by calorie restriction has generated much interest. In the present study, we have determined whether or not calorie restriction would affect the mutagenic response in rats treated with bleomycin (BLM) a radiomimetic drug that is associated with DNA damage by a free radical mechanism. Fourteen weeks after weaning, the rats were divided into two groups; ad libitum (AL)-fed and 40% calorie restriction. Both AL and calorie-restricted animals were injected with 2.5, 5.0 and 10.0 mg BLM/kg, or with phosphate-buffered saline (PBS), and they were killed 4 weeks post drug treatment. Lymphocytes from the spleens were seeded in 96-well microtiter plates to determine mutant frequency in the hypoxantine guanine phosphoribosyl transferase (Hprt) gene. The mutant frequency in the BLM-treated rats was higher in AL males (P=0.001), and AL females (P=0.0174) than in their calorie-restricted counterparts. The difference in mutagenic response relative to AL males and AL females appeared unrelated to a low percent cloning efficiency seen in the males, since the mean absolute number of Hprt mutant clones was higher in the AL males compared to the females. A reduction in animal weight by calorie restriction was significant in both sexes (P<0.001), but the dose effect appeared non-significant. The results indicate that calorie intake of 60% reduced the mutagenic response of BLM, a compound known to induce oxidative DNA damage, and suggest a possible decrease in ROS as a function of calorie restriction.

Animals↗

PubMed1997

Is there a role for corticosterone in expression of abnormal behaviour in restricted-fed fowls?

Growing parent stock (breeders) of meat-type chickens (broilers), subjected routinely to chronic food restriction, show increased pacing before a single daily meal and increased drinking and pecking at non-food objects (oral stereotypies) afterwards. Expression of these activities is correlated positively with the level of restriction imposed, and is thought to be controlled mainly by central dopaminergic mechanisms. There is published evidence that glucocorticoids can amplify dopamine mediated behaviours, and this paper describes four experiments examining the relationship between corticosterone and behaviour in individually caged broiler breeders. In Experiment 1 (with 3 levels of food restriction), plasma corticosterone concentration was correlated positively with the level of restriction imposed when blood samples were taken in the morning, but not when they were taken in the afternoon. This may be because corticosterone level declines from morning to afternoon with mild but not severe restriction. In Experiment 2 (severe restriction only), plasma corticosterone level did not change significantly with time of day, and mean values of individual birds were not correlated with their observed times spent in oral stereotypies. In Experiment 3 (severe restriction), object pecking increased in a dose-related way after systemic injection of 1-4 mg/kg corticosterone (significant) and 7.5-30 IU/kg ACTH (not significant), and 10-40 mg/kg metyrapone (corticosterone synthesis inhibitor) had no effect. In Experiment 4 (severe restriction), 180 mg/day metyrapone administered in food for 5 days reduced the plasma corticosterone response to injection of 15 IU/kg ACTH on the fourth day, but otherwise had no effect. Significant increases in drinker directed activity after injection of ACTH on the fourth day and 4 mg/kg corticosterone on the fifth day coincided with greatly elevated plasma levels of corticosterone. It is concluded that the oral stereotypies of restricted-fed broiler breeders do respond to induced increases in plasma corticosterone concentration that are supra-physiological, but there may be only a weak association between behaviour and corticosterone within the physiological range.

Adrenocorticotropic Hormone↗

PubMed1998

The role of specific macronutrient availability in the effect of food restriction on length of lactational diestrus in rats.

In lactating rats, food restriction for the first two weeks postpartum extends the period of lactational diestrus by about 1 week. In these studies we investigated whether this effect results from caloric restriction or the reduced availability of a specific macronutrient. In Experiment 1 lactating rats nursing litters of eight pups were assigned to one of four conditions: 1) ad lib. fed; 2) protein-restricted; 3) carbohydrate-restricted; and 4) fat-restricted. Animals in all the restricted conditions were given access to 50% of ad lib. intake of the appropriate nutrient for Days 1-14 postpartum and ad lib. access to the other two macronutrients. In Experiment 2, ad lib. supplementation from one macronutrient source was provided to lactating rats given restricted access to a composite diet. No differential effect of specific macronutrient deprivation or supplementation on length of lactational diestrus was observed in these studies. Thus, the results of both studies are consistent with the hypothesis that caloric restriction plays a primary role in inducing the prolongation of lactational diestrus in food-restricted rats.

Animals↗

PubMed2000

Feed restriction in young bulls alters the onset of puberty in relationship with plasma insulin-like growth factor-I (IGF-I) and IGF-binding proteins.

The objectives of this study were to evaluate the effect of feed restriction and re-alimentation on the onset of puberty and IGF status in peripubertal male calves and to compare the radioimmunoassay (RIA) and western ligand blotting (WLB) methods for bovine IGFBP-2. Twelve prepubertal 290 d-old Belgian Blue bulls (mean weight: +/- 290 kg) were randomly assigned in three groups: a control group (NG; n = 4) receiving a classic fattening diet to induce "normal" growth (1.48 kg/d), a feed restricted group (RG; n = 4) to obtain reduced growth (0.50 kg/d) and, a severely restricted group (SG; n = 4) to nearly stop growth (0.08 kg/d). The feed restriction period was maintained over a period of 114 d. After the period of differential feeding, all animals received the control feed regime over a period of 100 d. Blood samples were collected at fortnightly intervals. Circulating IGF-I was measured by RIA whereas plasma IGFBPs was evaluated by WLB; IGFBP-2 was additionally quantified by RIA procedure. At the beginning of the trial, IGF-I levels were low (<100 ng/ml) and similar in the three groups in accordance with prepubertal status. In the NG group, a progressive rise in IGF-I was observed from Day 42 to Day 142 whereas in the RG and SG groups, IGF-I levels did not change until the experimental restriction period ended. The delay of the rise in plasma IGF-I was longer for the SG group, IGF-I remained low until 2 wk after the end of the period of restricted feeding. Surprisingly, although differences were detected for IGF-I levels between the three groups, the IGFBP-2 and -3 data, evaluated by WLB could only discriminate between NG and SG group and not between NG and RG. However, by using a RIA method, an IGFBP-2 decrease was observed in the NG group coincident with increasing IGF-I levels. For both RG and SG groups, IGFBP-2 levels remained high throughout the feed restriction period whereas plasma IGFBP-2 levels declined upon feeding in both groups. During this feed restriction period, IGFBP-2 was significantly lower in NG than in RG or SG groups. Moreover, SG group animals had higher levels in plasma IGFBP-2 than RG animals. In conclusion, puberty is characterized by developmental changes in plasma IGF-I and IGFBPs that were altered by feed restriction. Moreover, RIA evaluation of plasma IGFBP-2 is able to better reflect group differences than WLB.

Animals↗

PubMed1997

Blood pressure and metabolic responses to moderate sodium restriction in isradipine-treated hypertensive patients.

This multicenter, randomized, controlled clinical trial assessed the influence of sodium chloride intake on the antihypertensive effect of the calcium channel blocker isradipine. Participants with uncomplicated hypertension controlled by isradipine entered a 4-week sodium-restricted (60 to 80 mmol/24 h) period. Participants with urinary sodium levels < 120 mmol/24 h (n = 99) were randomized to placebo or sodium chloride (100 mmol/24 h) for 4 weeks, and then crossed over to the alternative treatment for an additional 4 weeks. Mean baseline systolic blood pressure was 151.9 +/- 16.7 mm Hg (mean +/- SD). During open-label isradipine treatment, systolic blood pressures for ad libitum sodium chloride and restriction were 134.1 +/- 11.1 and 132.1 +/- 12.2 mm Hg respectively; for double-blind sodium chloride restriction and supplementation: 133.6 +/- 12.6 and 138.5 +/- 12.8 mm Hg (P < .01). Urinary sodium excretion values for open-label isradipine ad libitum versus restricted were 140.6 +/- 61.9 versus 76.9 +/- 32.4 mmol/24 h; for double-blind restricted versus supplemented, sodium excretion was 120.5 +/- 68.9 v 175.9 +/- 68.7 mmol/24 h (P < or = .0001). Changes in urinary sodium excretion were not predictive of variations in blood pressure. Urinary sodium excretion during sodium restriction correlated directly with HDL-cholesterol (P < .02) and inversely with total cholesterol:HDL-cholesterol (P = .02), despite decreased total and saturated fat intake (P < .01). Sodium restriction was associated with significant reductions (P < .01) in virtually all macronutrients and electrolytes, and thus had an adverse impact on overall nutrition. The antihypertensive action of isradipine was not enhanced by dietary sodium chloride restriction, and the lipoprotein profile was least favorable with sodium chloride restriction.

Adult↗

PubMed2003

Food restriction attenuates blood lipid peroxidation in carbon tetrachloride-intoxicated rats.

OBJECTIVE: We investigated whether food restriction offers protection against the toxicity of carbon tetrachloride (CCl(4)) and, if so, at what percentage of restriction. METHODS: The effects of food restriction (75% and 50% of food intake) and food restriction followed by CCl(4) treatment on lipid peroxidation and antioxidant enzymes were studied in female Wistar rats. A single dose of CCl(4) (3 mL/kg of body weight, subcutaneous) was administered at the end of the 30-d feeding period. RESULTS: The magnitude of increase in lipid peroxidation was less after CCl(4) treatment in food-restricted animals than in animals fed ad libitum (control), whereas alanine transaminase, aspartate transaminase, and alkaline phosphatase activities in plasma were enhanced due to CCl(4) treatment. The magnitude of increase in the marker enzymes was less in food-restricted animals than in control animals. Erythrocytes from food-restricted rats were more resistant to hydrogen peroxide-induced peroxidation than were those from control rats. The activities of superoxide dismutase, catalase, glutathione peroxidase, and glutathione-S-transferase were higher in food-restricted animals. CONCLUSIONS: The present results suggested that food restriction can minimize drug-related increases in peroxidation and protect the system against drug toxicity, presumably by induction of antioxidant potential.

Alanine Transaminase↗

PubMed2003

Preliminary observations on the effects of sleep time in a sleep restriction paradigm.

OBJECTIVE: To evaluate of the effect of 7 days of sleep restriction--with sleep placed at the beginning of night or early morning hours - on sleep variables, maintenance of wakefulness test, and serum leptin. METHODS: After screening young adults with questionnaires and actigraphy for 1 week, eight young adult males were recruited to participate in a sleep restriction study. The subjects were studied for baseline data for 2.5 days, with 8.5 h per night in bed, and then over 7 days of sleep restriction to 4 h per night with a 22:30 h bedtime for half the group and a 02:15 h bedtime for the other half. At the end of study, after one night of ad libitum sleep, subjects again had 2 days of 8.5 h in bed. Wakefulness was continuously verified and tests, including Maintenance of Wakefulness (MWT), were performed during the scheduled wake time. Blood was drawn six times throughout the 24 h of the 7th day of sleep restriction and after 2 days of the post-restriction schedule. RESULTS: There was individual variability in response to sleep restriction, but independent of group distribution, MWT was significantly affected by sleep restriction, with the early morning sleep group having less decrease in MWT score. Sleep efficiency was also better in this group, which also had shorter sleep latency. Independent of group distribution there was a greater increase in the percentage of slow wave sleep than rapid eye movement sleep, despite a clear internal variability and variability between subjects. Peak serum leptin was significantly decreased with 7 days of sleep restriction for all subjects. CONCLUSION: Sleep restriction to 4 h affected all subjects, but there were individual and group differences in MWT and sleep data. In this group of young adult males (mean age 19 years), there was a better overall adaptation to the early morning sleep, perhaps related to the general tendency in most adolescents to present some phase-delay during late teen-aged years.

Adolescent↗

PubMed2001

Highly alpha- and beta-selective radical C-glycosylation reactions using a controlling anomeric effect based on the conformational restriction strategy. A study on the conformation-anomeric effect-stereoselectivity relationship in anomeric radical reactions.

We hypothesized that, because the stereoselectivity of anomeric radical reactions was significantly influenced by the anomeric effect, which can be controlled by restricting the conformation of the radical intermediate, the proper conformational restriction of the pyranose ring of the substrates would therefore make highly alpha- and beta-stereoselective anomeric radical reactions possible. Thus, the conformationally restricted 1-phenylseleno-D-xylose derivatives 9 and 10, restricted in a (4)C(1)-conformation, and 11 and 12, restricted in a (1)C(4)-conformation, were designed and synthesized by introducing the proper protecting groups on the hydroxyl groups on the pyranose ring as model substrates for the anomeric radical reactions. The radical deuterations with Bu(3)SnD and the C-glycosylation with Bu(3)SnCH(2)CH [double bond] CH(2) or CH(2) [double bond] CHCN, using the (4)C(1)-restricted substrates 9 and 10, afforded the corresponding alpha-products (alpha/beta = 97:3-85:15) highly stereoselectively, whereas the (1)C(4)-restricted substrates 11 and 12 selectively gave the beta-products (alpha/beta = 1:99-0:100). Thus, stereoselectivity was significantly increased by conformational restriction and was completely inverted by changing the substrate conformation from the (4)C(1)-form into the (1)C(4)-form. Ab initio calculations suggested that the radical intermediates produced from these substrates possessed the typical (4)C(1)- or (1)C(4)-conformation, which was similar to that of the substrates, and that the anomeric effect in these conformations would be the factor controlling the transition state of the reaction. Therefore, the highly alpha- and beta-selective reactions would occur because of the anomeric effect, which could be manipulated by conformational restriction of the substrates, as expected. This would be the first radical C-glycosylation reaction to provide both alpha- and beta-C-glycosides highly stereoselectively.

Free Radicals↗

PubMed1999

Life-long dietary restriction modulates the expression of collagens and collagen-binding heat shock protein 47 in aged Fischer 344 rat kidney.

It has been shown that the expression of HSP47 and collagens is substantially increased in the sclerotic/fibrotic process in various organs, including kidney. However, the factors regulating the increased expression of HSP47 are not yet clear. In this study, we examined the effect of dietary restriction for the expression of collagens and collagen-binding HSP47 in the kidneys of 6- and 24-month-old male Fischer 344 (F 344) rats fed ad libitum or 30% diet-restricted. No significant histological alteration was found in the kidneys of 6-month-old fed or diet-restricted rats. Kidneys obtained from 24-month-old freely fed rats showed glomerulosclerosis with marked tubulointerstitial damage including interstitial fibrosis, while in the kidneys of 24-month-old diet-restricted rats, renal damage was remarkably less than those noted in 24-month-old freely fed rat kidneys. Immunohistochemical analysis showed an increased accumulation of type I, type III and type IV collagens in areas of glomerulosclerosis and interstitial fibrosis in old rat kidneys. Dietary restriction significantly reduces renal accumulation of collagens in old age. Aging enhanced expression of HSP47 in 24-month-old freely fed rat kidneys whereas dietary restriction suppressed its expression in 24-month-old diet-restricted rat kidneys. Also, phenotypic alterations of mesangial cells and interstitial cells (immunopositive for alpha-smooth muscle actin), glomerular epithelial cells (immunopositive for desmin) and tubular epithelial cells (immunopositive for vimentin) were seen in 24-month-old freely fed rat kidneys and found to express HSP47. Dietary restriction significantly diminished phenotypically altered renal cells in 24-month-old rat kidneys. Our results suggest that increased expression of HSP47 is associated with age-related renal damage and that diet-restricted alteration of its expression is associated with the modulation of age-associated renal sclerosis/fibrosis.

Actins↗

PubMed2004

Sexual dimorphism in the response of adipose mass and cellularity to graded caloric restriction.

OBJECTIVE: To investigate the effects of mild to moderate caloric restriction on parameters of body growth, fat mass, and adipose tissue cellularity in female and male Wistar rats. RESEARCH METHODS AND PROCEDURES: Three-month-old female and male Wistar rats were subjected to a chronic, mild to moderate caloric restriction paradigm (5%, 10%, or 20% reduction in caloric intake from ad libitum values) for 6 months. This was accomplished using a unique automated feeder system tailored to the food consumption levels of individual rats. Body weight and length, weight of lean organs, regional adipose mass, and adipose cellularity were measured before and after the diet restriction. RESULTS: Caloric restriction produced proportional decelerations in body weight increases in both genders, without significant changes in body length or lean organ mass. Marked and disproportional reductions in regional adipose tissue mass were produced at all levels of food restriction (even at 5% restriction). An unexpected finding was that in response to graded caloric restriction, female rats preserved adipose fat cell number at the expense of fat cell volume, whereas the converse was seen for male rats. DISCUSSION: These studies demonstrate a sexual dimorphism in the response to mild to moderate degrees of chronic caloric restriction. At low levels of caloric restriction, it is possible to affect regional adipose mass and cellularity while preserving lean organ mass.

Adipocytes↗

PubMed1993

The regulation of hepatic carbon flux by pyruvate dehydrogenase and pyruvate dehydrogenase kinase during long-term food restriction.

The present study investigated the effects of chronic food restriction (achieved by limiting access to food to 2 h daily for up to 8 weeks) on the activity of the active form of pyruvate dehydrogenase (PDHa) in liver. Accelerated and exaggerated activation of hepatic PDH in response to a meal, previously demonstrated to occur within 10 days of food restriction, was demonstrated to persist for 4 and 8 weeks of food restriction, despite a food intake of only 50-60% of controls. Activation of hepatic PDH during feeding in rats subjected to food restriction for 4 weeks was dependent on continued food intake. As a consequence, hepatic PDHa activities in food-restricted rats were suppressed relative to controls for 19 h of the 24 h daily cycle. Curve-fitting by second-order polynomial regression analysis demonstrated a significant positive correlation between hepatic PDHa activity and lipogenic rate over the range of PDHa activities observed during the 2 h feeding period. Increased lipogenesis during feeding in food-restricted rats was not at the expense of hepatic glycogen synthesis or deposition; measurement of concurrent rates of glycogenesis and lipogenesis revealed simultaneous flux through both pathways, but specific activation of lipogenesis. The accelerated re-activation of hepatic PDH observed within 1 h of feeding in rats subjected to 4 weeks of food restriction was facilitated by a failure of the 22 h interprandial fasting period to induce a stable increase in hepatic PDH kinase activity. The present study indicates differential regulation of hepatic PDH kinase activity during periods of food withdrawal between food-restricted rats and starved/re-fed control rats. Such regulation occupies a critical role in determining the rate of activation of hepatic PDH during feeding. In turn, increased activity of hepatic PDHa during feeding in food-restricted rats bears a close positive relationship with hepatic lipogenic rate.

Animals↗

PubMed1996

Effect of dietary protein restriction on liver transcription factors.

The transcription of several genes that are preferentially expressed in the liver, including the serum albumin, transthyretin and carbamyl phosphate synthetase-I genes, is specifically decreased in animals consuming inadequate amounts of dietary protein. The high level of transcription of these genes in the liver is directed in part by a number of liver-enriched transcription factors, including hepatocyte nuclear factors (HNF)-1, -3, and -4, and proteins of the CCAAT/enhancer-binding protein (C/EBP) family. In the present study, we investigated the possibility that the co-ordinate decrease in transcription of the nutritionally sensitive genes in protein-deprived rats results from altered activity of one or more of the liver-enriched transcription factors. For HNF-4, Western blots indicated no change in the level of nuclear HNF-4 protein in liver of protein-deprived animals, whereas we observed a 40% reduction in the DNA binding activity of HNF-4 as measured by electrophoretic mobility shift assay (EMSA). Furthermore, the binding affinity of HNF-4 for DNA was unaltered by dietary protein deprivation, while the number of HNF-4 molecules able to bind to DNA (Bmax) was reduced, as determined by Scatchard analysis. This indicates that in the protein-restricted rats a portion of the pool of HNF-4 protein is inactivated or otherwise prevented from binding to DNA. The overall DNA binding activity of C/EBP alpha and beta was increased in protein-restricted animals. This change occurred in the absence of a change in the amount of the full-length forms of these two proteins, quantified by Western blotting. Interestingly, dietary protein restriction specifically increased the level of a truncated form of C/EBP beta (liver-enriched transcriptional inhibitory protein, LIP), which is a protein dominant negative inhibitor of C/EBP function. Analysis of HNF-3 DNA-binding activity by EMSA revealed that HNF-3 alpha and beta DNA binding was increased and that HNF-3 gamma DNA-binding activity was unchanged in protein-restricted animals. We also detected two apparently novel shift complexes with the HNF-3 probe by EMSA, both of which were decreased in protein-restricted animals. HNF-1 DNA-binding activity was increased by dietary protein restriction. We also examined the effect of protein restriction on the DNA-binding activity of two ubiquitous transcription factors, NF1 and Sp1. The DNA binding activity of the major NF1 isoforms was unchanged whereas the binding activity of Sp1 was increased in the protein-restricted animals. In summary, restriction of dietary protein resulted in a number of specific changes in the DNA-binding activity of various transcription factors. Because transcriptional activation typically involves the synergistic action of more than one transcription factor, small changes in the amount/activity of several factors, could have a strong net effect on the transcription of many genes.

Animals↗

PubMed2002

Prevention of obesity-linked renal disease: age-dependent effects of dietary food restriction.

BACKGROUND: Hyperphagic obese Zucker rats develop glomerular injury and die of renal disease, an outcome prevented by food restriction at an early age. We examined the effects of food restriction imposed at different ages on systemic, renal hemodynamic, and hormonal changes to gain insight into the mechanisms of obesity-linked glomerular injury. METHODS: At 6 weeks of age obese Zucker rats were either fed ad libitum or were restricted in food intake at various ages (6, 12, 26, or 50 weeks) to that consumed by lean Zucker rats (14 g/day). Every four weeks 24-hour urine collections, blood pressure, and venous blood samples were obtained until the end of study (60 weeks). RESULTS: Food restriction at 6 or 12 weeks of age prevented glomerular injury and hypertrophy and delayed the development of hypertension, hypercholesterolemia, and hyperinsulinemia. Food restriction at 26 weeks of age reduced proteinuria, while restriction at 50 weeks prevented further increases in proteinuria without altering pre-existing hypercholesterolemia, hypertension, or hyperinsulinemia. Hypertriglyceridemia and glomerular hyperfiltration in the obese animals were reversed at any age by food restriction. Plasma leptin levels were elevated in all obese groups. CONCLUSIONS: (1) Early food restriction provided the greatest metabolic and renal benefits; (2) glomerular injury correlated with hyperphagia-induced hyperfiltration and hypertriglyceridemia and both were prevented by food restriction; (3) hypercholesterolemia was due to an increase in LDL and/or VLDL cholesterol; and (4) leptin does not directly contribute to glomerular injury in the obese Zucker rat.

Age Factors↗

PubMed2002

Characteristics associated with fear of falling and activity restriction in community-living older persons.

OBJECTIVES: To identify the characteristics associated with restricting activity because of fear of falling (activity restriction) and to determine which characteristics distinguish older persons who restrict activity from those who have fear of falling but do not restrict their activities (fear of falling alone). DESIGN: Population-based cross-sectional study. SETTING: General community. PARTICIPANTS: One thousand sixty-four community-living persons aged 72 and older. MEASUREMENTS: Candidate predictors were identified from the following domains: demographic, health status, physical, psychosocial, and fall-related. The outcome measure was the report of no fear of falling, fear of falling alone,or activity restriction. RESULTS: Fifty-seven percent of the cohort reported no fear of falling, 24% reported fear of falling alone, and 19% reported restricting activity. The proportion of participants with poor health status, slow timed physical performance, activities of daily living disability, and poor psychosocial function was highest in those with activity restriction, intermediate in those with fear of falling alone, and lowest in those with no fear of falling. Of participants with fear of falling, characteristics independently associated with activity restriction were history of an injurious fall, slow timed physical performance, two or more chronic conditions, and depressive symptoms. CONCLUSION: Older persons who restrict activity are more physically frail and have a greater burden of chronic conditions and depressive symptoms than those who have fear of falling alone. These differences between persons with fear of falling may guide the refinement of clinical interventions and preventative programs.

Accidental Falls↗

PubMed2001

Short-term dietary energy restriction reduces lean body mass but not performance in physically active men and women.

We studied the effect of moderate, short-term energy restriction on physical performance in physically fit men (n = 13) and women (n = 11) in a controlled clinical research setting with a metabolic kitchen, exercise testing laboratory and training facility. The experiment consisted of a 10 d baseline period followed by either 2 wk of dietary energy restriction (750 kcal/d; n = 16) or energy balance (control; n = 8). During this 24 day study, exercise energy expenditure averaged 465 +/- 5.7 kcal/d in all subjects and was accomplished through treadmill running at a self-selected pace. Body weight was maintained in the control group (-0.36 +/- 0.24kg), but energy restriction resulted in weight loss of -1.29 +/- 0.16 kg (p < 0.001). There was a trend for lean body mass to decline more in the energy restriction group (p = 0.093), accounting for 61% of the weight loss, and urinary nitrogen excretion also tended to be higher in the energy restriction vs. control group (i.e., 13.2 +/- 1.1 vs. 11.2 +/- 1.0g/d; p = 0.089). Muscle strength (leg & shoulder press; 1 repetition maximum) was maintained or increased during the energy restriction period. Muscle endurance, assessed by leg squats to fatigue, and 5 mile run time improved following two weeks of energy restriction or balance. Anaerobic capacity (Wingate Test) increased slightly in the restriction (+ 368 +/- 219 joules) but declined in the control group 649 +/- 288 joules; p<0.05). We conclude that short-term (2 weeks) moderate energy restriction (approximately 750 kcal/d) results in weight loss but does not impair performance in physically fit young men and women.

Adult↗

PubMed1994

Reduction in hyperglycemia by mild food restriction in streptozotocin induced diabetic rats improves insulin sensitivity.

Hyperglycemia has been shown to contribute to the development and maintenance of insulin resistance in diabetic subjects and animal models of diabetes. Normalisation of circulating glucose levels is effective in restoring insulin action. The aim of the current study was to investigate the effects of mild food restriction on hyperglycemia in streptozotocin (STZ) treated (50 mg/kg) diabetic rats and to determine if the reductions in glycemia following food restriction were sufficient to alter insulin sensitivity. Food restriction was achieved in STZ diabetic and normal rats by limiting food access to two one-hourly meals daily and further in normal rats by restricting the feeding period to a single two-hour meal daily. Food intake was lowered by 39.7% (p < 0.01) in the food restricted STZ rats, without significant alteration in weight gain over 4 weeks. Similarly, in the normal rats once and twice daily meals lowered food intake by 37.6% and 21.6% when compared to the ad-libitum fed group, respectively. After 3 weeks food restriction in the STZ diabetic rats mean plasma glucose levels over a 12 hour period were reduced by 13.9%, glucose levels after a 6 hr fast were reduced by 33% (p < 0.05). Plasma insulin levels remained unaltered by food restriction. After 4 weeks food restriction in STZ diabetic rats basal glucose turnover was reduced (p < 0.05) and the metabolic clearance rate of glucose (MCR) increased (p < 0.05). During the hyperinsulinemic clamp hepatic glucose output (HGO) was suppressed and MCR elevated more effectively in the food restricted STZ than the ad-libitum STZ rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Mapping of herpes simplex virus 1 genes with mutations which overcome host restrictions to infection.

Earlier studies have shown that the thymidine kinase-negative baby hamster kidney (BHKTK-) cell lines expressing constitutively the herpes simplex virus 1 (HSV-1) glycoprotein D (gD), designated BJ, restrict infection by HSV-1 at the level of virus entry. U10, a HSV-1 mutant not restricted by the BJ cells, carried the substitution of proline for Leu25 in the gD gene, suggesting that gD encodes a specialized domain which precludes virus entry into cells expressing gD. Analyses of a new series of 36 unrestricted viral mutants showed the following. (i) Only two mutants contained mutations at a site which did not overlap with the previously reported mutation. A representative of a previously mapped mutant and one of the two new mutants were examined in detail. Thus, in the gD of mutant U30 Ala185 was replaced by threonine, whereas in gD of U21, Ala185 and Leu25 were replaced with threonine and proline, respectively. U30 and U21 multiplied better than the wild-type parent virus in the parental BHKTK- cells. (ii) Transfer of the gD gene from U21 or U30 to wild-type parent virus or to the gD- virus FgD beta yielded recombinants which, while capable of infecting BJ cells, were considerably less efficient than the parent unrestricted mutants, suggesting that the latter contained additional mutations which were responsible in part for the unrestricted phenotype. Conversely, marker rescue of mutant viruses with wild-type gD reduced but did not abrogate entirely the unrestricted phenotype. (iii) Mutations in gD which conferred the unrestricted phenotype were not random. (iv) gD plays a role in the restriction, inasmuch as preincubation of cells expressing gD with antibodies to gD abolished restriction. (v) In mutant R5000, the gD substitution Ser140 to Asn was capable of overcoming a restriction of a BHKTK- clonal line which does not express gD but conferred very low ability to replicate on BJ cells. We conclude that (a) uncloned stocks of BHKTK- cells exhibit a low level restriction to infection with wild-type virus, (b) clonal lines of BHKTK- cells which vary with respect to the stringency of restriction express either allelic genes differing in the properties of their products or products of different genes, and (c) both the restricted and unrestricted phenotypes reflect the interactions of gD with these cellular products. The implications of these conclusions with respect to the restriction imposed on BHK cells by the expression of gD are discussed.

Animals↗

PubMed1994

Effects of feeding restriction and meal pattern of a sugar beet-containing diet and control diet on nutrient digestibility, plasma lipid concentrations and postprandial triacylglycerol response in broiler chickens.

Broiler chickens were fed on a control diet based on maize or a diet containing sugar-beet-pulp fibre (Beetfiber) at an inclusion level of 46 g/kg. Diets were provided ad lib. or at a restricted level either once daily or three times daily. On days 13 and 20, chickens fed on the ad lib. control and sugar-beet-pulp-containing diets generally weighed more and had poorer feed conversion ratios than chickens given the restricted control and sugar-beet-pulp-containing diets respectively. Furthermore, chickens given the restricted diets once daily had greater body weights and generally improved feed conversion efficiencies compared with chickens given the restricted diets three times daily. Generally, elevated plasma lipid concentrations were observed amongst chickens given the restricted diets once daily compared with chickens fed ad lib. as well as the restricted diets three times daily, while chickens fed on restricted diets three times daily had plasma lipid concentrations intermediate between those fed ad lib. and once daily. In a plasma triacyglycerol response study on day 22, feeding of sugar-beet-pulp-containing diets generally reduced postprandial triacylglycerol concentrations and delayed triacylglycerol response relative to chickens given the control diets either ad lib. or restricted, which may indicate gastrointestinal adaptation to feeding of a fibre-rich diet. Postprandial triacylglycerol concentrations observed for chickens receiving restricted diets were increased compared with chickens given the respective ad lib. diets, indicating adaptation of chickens to reduced feed frequency. On day 25, feeding of sugar-beet-pulp-containing diets decreased digesta dry matter content and ileal organic matter digestibility. Chickens given sugar-beet-pulp-containing diets generally had, on day 25, increased caecal short-chain fatty acid (SCFA) concentrations in comparison with chickens given the ad lib. control diet, indicating increased fermentation of dietary components. It is also noteworthy that the greatest SCFA concentrations were observed amongst chickens given the control diet once daily, suggesting enhanced caecal fermentation capacity. This may have been a consequence of increased bacterial activity and caecal hypertrophy due to infrequent feeding of a low-fibre diet.

Animals↗