Factors influencing required dietary nutrient concentrations.
A review of the genetic and environmental factors that must be considered when forming nutritionally adequate diets for specific laboratory animal colonies.
Journal Article↗
Biomedical subjects
J J Knapka
Publications and source records attributed to J J Knapka.
Nutrition of rodents.
Access to a diet that provides adequate nutrition is one of the most important environmental factors influencing the well-being of rodent colonies. The dietary ingredient and nutrient composition, as well as the potential biological and chemical contaminant concentrations, are factors for consideration in selecting diets for a specific rodent colony. Estimated nutrient requirements have been published for the rodent species that are commonly used in biomedical research. The nutrient concentrations in adequate diets for other captive rodent species that are not used in biomedical research are more difficult to obtain. However, reasonable estimates of their nutrient requirements can be obtained by extrapolation of data from rodent species of a similar metabolic weight and size or from nutrient concentrations of diets that have a history of acceptable performance in the species of interest. Captive rodent colonies should be provided with nutritionally balanced diets with only limited amounts of succulent foodstuffs. The practice of feeding rodent colonies specific cereal grains is discouraged, since no single grain provides a balanced rodent diet.
Animal Feed↗
Dietary restriction slows age pigment accumulation in the retinal pigment epithelium.
PURPOSE: The accumulation of age pigment, or lipofuscin, in postmitotic cells appears to be a universal feature of the aging process in animals. In mammals, the lipofuscin content of the retinal pigment epithelium (RPE) increases progressively during senescence. Dietary restriction has been shown to slow the rate at which many biologic parameters change during aging. Experiments were conducted to determine if dietary restriction alters the rate of age pigment accumulation in the RPE. METHODS: Male Wistar rats were placed on one of three dietary regimens starting at weaning. One group was fed a nutritionally complete diet ad libitum. Another group was fed the same diet but was only allowed to consume 60% as much food daily as the ad libitum group ate. The final group was fed ad libitum a nutritionally complete diet that had a lower caloric density per gram than the diets fed to the other animals primarily because of the replacement of carbohydrate with oat fiber. Ultrastructural morphometric analysis was used to determine the RPE age pigment content in the first group at 6 months of age, and in all of the groups at 18 months of age. RESULTS: Dietary restriction, achieved either by reducing total food intake or by reducing the caloric content of the diet, resulted in significant decreases in RPE lipofuscin accumulation. CONCLUSIONS: Dietary restriction provides a relatively simple means by which RPE age pigment content can be modulated. This should prove useful in assessing the role of RPE lipofuscin accumulation in age-related retinal disorders. That the oat fiber diet fed ad libitum was almost as effective as restriction of total food intake in slowing RPE age pigment accumulation indicates that the effect of restricted caloric intake is not mediated by almost constant hunger.
Aging↗
Dietary restriction in nonhuman primates: progress report on the NIA study.
Rhesus and squirrel monkeys have been fed a semisynthetic diet at approximately ad libitum or 30% reduced levels for 3.5 (rhesus group 2) to 4.5 (rhesus group 1 and squirrel) years. Animals have maintained excellent health status as determined by physical examinations, hematology, and blood chemistry. While relative rates of body weight gain in restricted group 1 rhesus and squirrel monkeys have been markedly reduced, DR effects on crown-rump length (body height) have been variable. In addition, numerous physiological and biochemical parameters have been measured, and several exhibit significant cross-sectional age effects. Interestingly, several of these also exhibit possible species and genotype (group 1 and 2 rhesus) differences. A number of physiological parameters are emerging that might be altered by DR; however, further explanation of these effects awaits more extensive and detailed analyses.
Aging↗
High sucrose diets increase blood pressure of both salt-sensitive and salt-resistant rats.
We examined the effects of a diet relatively high in sugar and low in protein content on systolic blood pressure (SBP) in rats with known pressure responses to salt (NaCl) in order to compare "sugar/protein sensitivity" to "salt sensitivity." Dahl salt-sensitive (DSS) and salt-resistant (DSR) rats were fed one of two low salt diets containing either high sugar (sucrose 51.5% w/w)/low protein (14.6% w/w) or low sugar (sucrose 12.5% w/w)/high protein (52.2% w/w) content. After 3 weeks, the DSS ingesting the high sugar diet/low protein diet developed significantly elevated SBP relative to DSR eating the same high sugar/low protein diet and the DSS and DSR consuming the low sugar/high protein diet. After 2 to 3 months, the SBP of DSR eating the high sugar diet began to rise markedly and eventually both DSS and DSR ingesting the high sugar/low protein diet maintained similarly elevated SBP, significantly higher than DSS and DSR ingesting the low sugar/high protein diet. When Fischer 344 rats, a normotensive, salt-resistant rat strain, were fed the high sucrose/low protein diet, SBP also rose significantly into hypertensive ranges over 2 to 3 months. Since the SBP of DSR and Fischer 344 rats are not influenced to any great extent by high salt intake, even after prolonged exposure, the SBP rise associated with the high sugar/low protein diet may be via a mechanism different from salt-induced hypertension. However, it is also possible that the high sugar/low protein diet creates in DSS and DSR the situation responsible for salt induction in DSS.(ABSTRACT TRUNCATED AT 250 WORDS)
Administration, Oral↗
Prevention of cataracts in pink-eyed RCS rats by dark rearing.
Royal College of Surgeons rats have hereditary retinal degeneration and associated posterior subcapsular opacities (PSO) of the lens, detectable by slitlamp at 7-8 postnatal weeks in both pink- and black-eyed rats. The retinal degeneration is intensified by light, especially in pink-eyed rats. A fourth of pink-eyed rats developed mature cataracts by 9-12 months of age, but black-eyed rats whose retinas are protected from light by pigmented irises and pigment epithelium rarely have mature cataracts (3% or less), indicating light may be a factor in cataractogenesis. Prior work had shown that dark rearing reduced the rate of retinal degeneration in pink- but not black-eyed rats, but cataracts were not studied. In the present work, pregnant pink-eyed females were placed in a darkroom 1 week before parturition. Pups were removed over intervals at 20-85 postnatal days for: (a) microscopic study of fresh lenses and of fixed, stained retina and lens, and (b) counts of cells mm-2 of the web-like vitreous cortex after it had been dissected free. The macrophage-like cells are a quantitative index of immune reaction to retinal damage. At 50-53 postnatal days, in pink-eyed cyclic light reared RCS, the mean number of macrophages was 4.6-fold that in congenic controls, but in those that were dark reared it was only 1.4-fold. This was less than the increase in cyclic light reared black-eyed RCS (2.3-fold that in congenic black-eyed controls). Total absence of light reduced retinal degeneration and the number of macrophages, and prevented PSO detectable microscopically.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Dietary trans fatty acids modulate erythrocyte membrane fatty acyl composition and insulin binding in monkeys.
The substitution of trans- for half of the cis-monounsaturated fatty acids in the diet of Macaca fasicularis monkeys resulted in alterations in erythrocyte fatty acid composition and insulin receptor properties but not in membrane fluidity. Both cis and trans diets contained 10% fat and similar fatty acid compositions, except that approximately 50% of the cis-octadecenoate (c-18:1) in the cis diet was replaced with trans-octadecenoate isomers (t-18:1) in the trans diet. Compared with the cis diet, the trans diet resulted in the incorporation of approximately 11% t-18:1, an approximately 50% decrease in c-18:1, an approximately 16% decrease in total saturated fatty acids, and an approximately 20% increase in 18:2(n-6) in erythrocyte membrane lipids. The increase in 18:2(n-6) may reflect on homeostatic mechanisms designed to maintain overall membrane fluidity, as no diet-related changes in fluidity were observed with diphenylhexatriene steady state fluorescence polarization. Values observed for insulin binding and insulin receptor number were higher and binding affinity was lower in monkeys fed the cis diet. In the absence of an effect on overall membrane fluidity, altered receptor activity suggests that insulin receptor activity is dynamic, requiring specific fluid membrane subdomains or highly specific fatty acid-protein interactions.
Journal Article↗
Dietary restriction and aging: the initiation of a primate study.
Juvenile (1 yr) and adult (3-5 yr) male rhesus monkeys (Macaca mulatta) and juvenile (1-4 yr) and adult (5-10 yr) male squirrel monkeys (Saimiri sciureus) were fed a diet at or near ad libitum levels based on recommended caloric intake for age and body weight or fed 30% less of the same diet with this restriction gradually introduced over a 3-mo period. Analysis of body weights among these respective control and experimental groups from the first year of the study indicated that the monkeys undergoing dietary restriction were gaining weight at a markedly slower rate compared to control values. Actual food intake among diet-restricted groups had been reduced 22-24% below control levels. Periodic analysis of hematology and blood chemistry measurements over the first year of the study detected few significant differences between control and experimental groups to indicate that diet restriction was not detrimental to general health. When values obtained from hematology and blood chemistry measurements of juvenile and adult groups (control and experimental groups combined) were compared to ad libitum fed old monkeys from each species (greater than 18 yr for rhesus; greater than 10 yr for squirrel monkeys), many significant age differences were noted. Among the largest and most consistent findings in both species were age-related decreases in concentrations of lymphocytes, serum glutamic oxalacetic transaminase, serum glutamic pyruvic transaminase, alkaline phosphatase, and phosphates as well as the albumin/globulin ratio and the blood urea nitrogen/creatinine ratio. Age-related increases in serum globulin and creatinine concentrations were also found. These parameters as well as many others being implemented in the study will be monitored further to determine if diet restriction affects the rate of development as well as aging as observed in numerous rodent studies applying such nutritional manipulations.
Aging↗
Maintenance of cotton-top tamarins fed an experimental pelleted diet versus a highly diverse sweetened diet.
The future study of colon disease in captive callitrichid colonies may require manipulation of diets. The limited knowledge of the nutritional requirements for these species and the varied diets and supplementations fed to these animals in various colonies suggest the importance of testing the palatability and acceptability of diets for these primates. Individually housed cotton-top tamarins (Saguinus oedipus) were given either the regular Oak Ridge Associated Universities (ORAU) diet (monkey chow slurry, canned diet and supplements), a similar slurry using an experimental natural ingredient diet plus supplements, or the experimental diet without supplements. Neither dry food consumption, body weight, fecal output, nor the histological evaluation of the colons were affected by these diets. Daily intake of protein and calories were higher than previously reported estimates for the species. These results demonstrate that a natural ingredient non-sweetened pelleted diet is palatable for cotton-top tamarins for a period of 3.5 months, however, further testing over longer time periods is necessary. The nonnutritional (e.g. psychological) advantages of providing a highly diverse diet to primates housed in a relatively monotonous environment should be considered before adopting such a diet for an entire colony.
Animal Feed↗
Contaminant and nutrient concentrations of natural ingredient rat and mouse diet used in chemical toxicology studies.
The NIH-07 open formula natural ingredient rat and mouse ration is the standard diet for chemical toxicity and carcinogenicity studies conducted for the National Toxicology Program (NTP). Contaminant and nutrient concentrations were determined in 2 to 94 lots of this diet used in the NTP toxicology studies. All nutrient concentrations were equivalent to or greater than the requirements for rats and mice as set forth by the National Research Council. Aflatoxins, Hg, chlorinated hydrocarbons except methoxychlor, organophosphates except malathion, estrogenic activity, and Salmonella sp. were not present at the detectable levels. Fluorine, As, Cd, Pb, Se, N-nitrosodimethylamine, N-nitrosopyrrolidine, N-nitrosomorpholine, nitrate, nitrite, butylated hydroxyanisole, butylated hydroxytoluene, ethylene dibromide, methoxychlor, malathion, and trypsin inhibitor activity were present at or above the detectable levels. Five lots of diet had nitrosamine content of 100 to 273 ppb and 7 lots had 2.08 to 3.37 ppm of Pb. All other lots of NIH-07 diet used for NTP toxicology studies contained low levels of the contaminants. After determination of the contaminant concentrations in the 94 lots of diet and the contaminant concentrations in natural ingredients used in formulating NIH-07 diet, maximum allowable levels of contaminants were established and a flexible scoring system for acceptability of each lot of diet for chemical toxicology studies was developed. By prescreening ingredients such as fish meal for heavy metals and nitrosamines, and applying the flexible scoring system proposed, more than 95% of the lots of NIH-07 diet produced during the last 3 years had scores of greater than or equal to 95 out of 100 points and were considered acceptable for toxicology studies.
Animal Feed↗
Refined carbohydrate increases blood pressure and catecholamine excretion in SHR and WKY.
In spontaneously hypertensive (SHR) and normotensive (WKY) rats fed different diets, blood pressure (BP) increased significantly in both strains when the carbohydrate (CHO) source was from refined rather than from natural ingredients. This BP increase was observed whether sucrose, glucose, or starch was the principal CHO. Urinary excretion of norepinephrine, dopamine, and, to some extent, epinephrine also increased, while myocardial concentrations were unaffected. Despite a comparable elevation of catecholamine excretion in both SHR and WKY rats fed high amounts of refined CHO, the BP increases were greater in the former. The strain differences were explained by the known dissimilar response of their blood vessels to catecholamines. The results suggest that BP elevation after high CHO ingestion is mediated via increased catecholamine production and/or release, thus implying a neurogenic mechanism.
Age Factors↗
Refined carbohydrates affect blood pressure and retinal vasculature in spontaneously hypertensive and Wistar-Kyoto rats.
Spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats received diets differing in amount and source of carbohydrates (CHO). When the CHO was in excess and the source was refined sugar or starch rather than natural ingredients, blood pressure (BP) rose, more so in SHR. This BP increase was observed whether sucrose, glucose, fructose or starch was the principal CHO. Increased urinary excretion of norepinephrine, dopamine and epinephrine also occurred. After only 2-3 months retinal capillary basement membrane damage was demonstrated in SHR and WKY rats ingesting large amounts of sucrose. No similar changes occurred on a high-starch diet. The damage consisted of thickening of capillary basement membranes, loss of homogeneity, and debris inclusions. These results suggest: that high dietary ingestion of CHO in the form of refined CHO augments BP in SHR and WKY rats via increased catecholamine production and/or release, and that the temporally foreshortened experimental period offered by the SHR/WKY model may be valuable in the study of diet-induced retinopathies.
Animals↗
Dietary prevention of cataracts in the pink-eyed RCS rat.
The American Institute of Nutrition purified ingredient diet (AIN-76) prevented occurrence of mature cataracts associated with hereditary retinal degeneration in pink-eyed, tan-hooded Royal College of Surgeons (RCS) rats. Rats fed a natural ingredient open formula NIH diet or a closed formula commercial diet had a cataract incidence of 27-29% by 3 to 12 months of age. In contrast, only 1 of 50 rats fed the AIN diet developed a mature cataract in one year. When the NIH diet and the commercial diet were pelleted with 25% of ground sunflower kernels, rats fed these diets had a delay in onset and a reduced incidence of mature cataracts to 18% and 5%, respectively. No mature cataracts occurred in rats fed the AIN diet supplemented with 25% sunflower kernels. All diets were fed to the parental generation as well as the progeny (experimental group). The rats were reared at a low level of illumination (1-3 footcandles inside the cage) to minimize effects of light. Prevention of mature cataracts by the AIN purified diet suggests that diets permitting cataracts to occur may have a constituent at a concentration innocuous for normal rats but beyond the homeostatic control of the RCS rat. Posterior subcapsular cataracts of RCS rats are a model for cataracts associated with human hereditary retinal degenerations, such as retinitis pigmentosa and gyrate atrophy. Manipulation of dietary ingredients allowed by the use of the AIN diet may permit identification of nutrients, nutrient interactions of toxic factors involved in cataractogenesis and its prevention.
Animal Feed↗
Slit-lamp assessment of onset of cataracts in black-eyed, black-hooded retinal dystrophic rats.
Various types of hereditary retinal degeneration have associated posterior subcapsular cataract (PSC). It has been claimed that in the Royal College of Surgeons (RCS) rat model of hereditary retinal dystrophy, the cataract is manifested unpredictably and does not display Mendelian inheritance. It ws shown previously, however, that 100% of pink-eyed retinal dystrophic RCS rats had an onset of bilateral PSC at 7 to 8 weeks of postnatal age, and by 9 to 11 months, 23% of the animals had cataracts visible to the unaided eye. The congenic black-eyed retinal dystrophic RCS rat, however, is a better model for the generally more pigmented human eye. In the present work, it was found that 100% of black-eyed RCS rats had bilateral slit-lamp-detectable PSC beginning at 8 weeks of postnatal age, just as the pink-eyed rats did, despite the fact that dark-eye pigmentation is associated with a 10- to 35-day delay in the rate of degeneration in retinal areas other than the peripheral part of the inferior hemisphere. A higher incidence of mature cataracts in pink-eyed rats (23%) as compared with black-eyed rats (3%) suggests that the amount or intensity of light reaching the lens, retina, and pigmented epithelium may influence maturation of the cataract. However, if light is important in initiating the PSC, its influence was not decreased by dark pigmentation of the eye. RCS rats may be a model for an early onset type of human autosomal recessive retinal degeneration having a constant association of PSC.
Animals↗
Growth, kidney disease, and longevity of Syrian hamsters (Mesocricetus auratus) fed varying levels of protein.
Male and female hamsters were fed natural ingredient diets containing 6, 12, 18, or 24% protein. Differences in growth rate, feed consumption, kidney weight, serum chemistry (total protein, serum creatinine, blood urea nitrogen), and longevity were analyzed. The kidneys were examined microscopically and graded according to the severity of nephritis. The 6% protein diet resulted in the lowest frequency of nephritis, but the animals were significantly smaller and had shorter life spans than the remaining groups. The 12% protein diet initially promoted slower growth than 18 or 24% protein, but the differences in body weight eventually became insignificant. The 12% protein diet resulted in a higher frequency of nephritis than 6% protein, but lower than 18 or 24% protein. The 18 and 24% protein diets promoted the most rapid early growth as well as the highest frequency and most severe kidney lesions. Uremia did not appear to be a major cause of death. Longevity did not differ significantly among hamsters of either sex fed 12, 18, or 24% protein diets.
Animals↗
Effects of sunflower seed supplements on reproduction and growth of RCS rats with hereditary retinal dystrophy.
Both control and dystrophic pink-eyed RCS rats reproduced poorly when they were fed a standard laboratory rodent diet and were housed in conventional animal rooms unshielded from pathogenic influences. More prolific reproduction and improved growth of young were obtained with a commercial unsterilized closed formula pelleted rodent ration, supplemented with 25% sunflower seed kernels. The sunflower kernels contained a high concentration of vitamin E and 47% fat which was mostly unsaturated. Linoleic acid was 75% of the unsaturated fatty acids. The kernels also contained a higher concentration of selenium (0.8 mg/kg) than standard rodent diets. Effective absorption of the high vitamin E of the diet was shown by analyses of blood plasma of 50-day-old dystrophic and control rats, in which the alpha-tocopherol level was three-fold that in animals fed standard laboratory rodent diet. Dams fed the diet had calmer temperaments and improved lactation. Litters of 8-13 pups were produced, and the pups grew rapidly to weaning with 95% survival of the control strains and 75% survival of the dystrophic strain. Progeny fed the diet for 8-10 months after weaning did not manifest cataracts, which occurred in 23% of the pink-eyed dystrophic animals fed standard rodent diets.
Animal Feed↗
Effect of crude fat and crude protein on reproduction and weaning growth in four strains of inbred mice.
Diets made from natural ingredients were fed to four inbred strains of mice (BALB/cAnN, C3H/HeN, C57BL/6N and DBA/2N) to study the effects of different concentrations of dietary crude protein, 18% and 24% with crude fat concentrations of 4%, 8%, and 12% on reproduction and weanling growth. The parameters measured included the number of litters and pups born, the number of litters and pups weaned, weanling mortality and weanling weight. Neither crude protein nor crude fat concentrations had significant effects on any of the reproductive parameters tested. However, a significant fat x protein interaction was observed for reproduction. These results indicate that the absolute concentrations of crude protein and crude fat in diets for inbred mouse production are not as important as the ratio of these two nutrients. There was also a differential response in reproduction among the strains due to the level of fat which indicates different dietary requirements for fat among these four inbred strains for maximum reproduction. In contrast to the results for reproduction, crude protein and crude fat independently had significant effects on weanling weight, but there was no effect due to the ratio of the nutrients. There was a significant increase in the weanling growth rate for all four strains as the dietary fat level increased, but a decrease in growth rate as the protein level increased. The reduced growth rate due to the increased protein was not of the same magnitude for all four strains which indicates specific protein requirements among the strains for weanling growth.
Animals↗