Galactose effects on enterocyte differentiation in the mouse jejunum

The present work investigates the ability of galactose to affect enterocyte differentiation during normal development in vivo. Energy intake has also been varied to take account of the fact that galactose is poorly metabolized in mice. Brush-border lactase, alpha-glucosidase, dipeptidylpeptidase-IV, aminopeptidase N, alkaline phosphatase and microvillus length were measured as markers of enterocyte differentiation in mice fed diets containing galactose (G diet), corn oil (E diet) or galactose + corn oil (G + E diet). Maintaining mice on a G instead of E diet reduced brush-border lactase activity and enterocyte migration rates; alpha-glucosidase, dipeptidylpeptidase-IV, aminopeptidase N and microvillus length expression increased and alkaline phosphatase activity remained unchanged. Feeding the G + E diet restored enterocyte migration rates, lactase, aminopeptidase N and dipeptidylpeptidase-IV activities to values found in mice fed the E diet. Galactose stimulation of alpha-glucosidase and microvillus length expression was, however, fully maintained in mice fed the G + E diet. Present results show that enterocyte differentiation is affected independently by varying dietary galactose and energy levels; that galactose effects always increase and energy effects usually decrease expression of enterocyte components and that energy stimulation of lactase activity is exceptional.     

Dual control over microvillus elongation during enterocyte development

1. Previously determined logistic growth constants describing enterocyte microvillus development for a variety of species were analysed for possible interactions taking place between enterocyte migration rate (R) and the size of individual crypts (CD). 2. Microvillus elongation, the c-value of a logistic growth curve, was found to increase linearly with crypt depth and reciprocally with decreasing migration rate. The starting microvillus length of a basal crypt enterocyte, the a-value, also increased linearly with CD without being affected by R. 3. The mathematical equation describing the effects of CD and R on M, the maximal microvillus length, was M = 0.0016 CD + 0.073 CD/R, where M and CD are measured in micron and R in micron/hr. 4. The relationship found between R, CD and M is explained by suggesting that the crypt environment enables enterocytes to respond to an initiating signal imposed on cells as they begin to migrate onto villi. The possible nature of this putative signal is also discussed.     

Calorie consumption level influences development of C3H/Ou breast adenocarcinoma with indifference to calorie source

To analyze simultaneously the influence attributable to calorie consumption level and percentage of dietary fat on the spontaneous development of mammary adenocarcinoma, virgin female C3H/Ou mice were separated into five dietary groups. Four groups of mice were fed purified diets either ad libitum (16-18 kcal/mouse/day) or restricted 40% in calorie consumption (10-11 kcal/mouse/day), and diets contained either 4.5%, 7.5%, 67%, or 68% calories from fat. Mice that consumed isocaloric diets developed breast malignancy at a comparable pace. Consuming a diet in which fats were present only at levels sufficient to satisfy the threshold requirement of essential fatty acids, 4.5-7.5% of the total calories, or alternatively where dietary fat represented greater than 67% of the total calories consumed, did not significantly alter the tendency for breast tumor development. The pace and frequency with which tumors occurred reflected the host's level of calorie consumption. Mice consuming a high caloric diet, low or high in fat, tended to have a shortened latency to breast tumor formation, an increased incidence of breast tumors, elevated serum prolactin levels, elevated levels of antibodies to mouse mammary tumor virus, and elevated circulating immune complex levels.     

Comparative aspects of microvillus development in avian and mammalian enterocytes

1. Pieces of chicken mid-jejunum have been used to determine microvillus length in enterocytes located at different points along the crypt-villus axis to determine the positional dependence of microvillus elongation. 2. The rate at which enterocytes migrate along the crypt-villus axis has also been measured, by injecting tritiated thymidine into the same animals, to determine the time course of microvillus elongation. 3. In mammals it had been shown previously that the maximal rate of microvillus elongation correlated closely with the physical size of the intestinal crypt (Smith et al., 1984). Comparison of crypt size with maximal rate of microvillus growth in chickens showed this correlation to apply to both animal classes. 4. The maximal microvillus length of a chicken enterocyte was much longer (3.3 microns) and the rate of enterocyte migration much less (4.0 microns/hr) than values reported previously for mammalian intestines. 5. The possibility that some other factor in addition to crypt size is affecting microvillus growth is discussed.     

Role of Choline Deficiency in the Fatty Liver?Phenotype of Mice Fed a Low Protein,Very Low Carbohydrate Ketogenic Diet

Though widely employed for clinical intervention in obesity, metabolic syndrome, seizure disorders and other neurodegenerative diseases, the mechanisms through which low carbohydrate ketogenic diets exert their ameliorative effects still remain to be elucidated. Rodent models have been used to identify the metabolic and physiologic alterations provoked by ketogenic diets. A commonly used rodent ketogenic diet (Bio-Serv F3666) that is very high in fat (~94% kcal), very low in carbohydrate (~1% kcal), low in protein (~5% kcal), and choline restricted (~300 mg/kg) provokes robust ketosis and weight loss in mice, but through unknown mechanisms, also causes significant hepatic steatosis, inflammation, and cellular injury. To understand the independent and synergistic roles of protein restriction and choline deficiency on the pleiotropic effects of rodent ketogenic diets, we studied four custom diets that differ only in protein (5% kcal vs. 10% kcal) and choline contents (300 mg/kg vs. 5 g/kg). C57BL/6J mice maintained on the two 5% kcal protein diets induced the most significant ketoses, which was only partially diminished by choline replacement. Choline restriction in the setting of 10% kcal protein also caused moderate ketosis and hepatic fat accumulation, which were again attenuated when choline was replete. Key effects of the 5% kcal protein diet – weight loss, hepatic fat accumulation, and mitochondrial ultrastructural disarray and bioenergetic dysfunction – were mitigated by choline repletion. These studies indicate that synergistic effects of protein restriction and choline deficiency influence integrated metabolism and hepatic pathology in mice when nutritional fat content is very high, and support the consideration of dietary choline content in ketogenic diet studies in rodents to limit hepatic mitochondrial dysfunction and fat accumulation.     

Effect of Diets Containing Sucrose vs. D‐tagatose in Hypercholesterolemic Mice

Effects of functional sweeteners on the development of the metabolic syndrome and atherosclerosis are unknown. The objective was to compare the effect of dietary carbohydrate in the form of sucrose (SUCR) to D‐tagatose (TAG; an isomer of fructose currently used as a low‐calorie sweetener) on body weight, blood cholesterol concentrations, hyperglycemia, and atherosclerosis in low‐density lipoprotein receptor deficient (LDLr^−/−) mice. LDLr^−/− male and female mice were fed either standard murine diet or a diet enriched with TAG or SUCR as carbohydrate sources for 16 weeks. TAG and SUCR diets contained equivalent amounts (g/kg) of protein, fat, and carbohydrate. We measured food intake, body weight, adipocyte diameter, serum cholesterol and lipoprotein concentrations, and aortic atherosclerosis. Macrophage immunostaining and collagen content were examined in aortic root lesions. CONTROL and TAG‐fed mice exhibited similar energy intake, body weights and blood glucose and insulin concentrations, but SUCR‐fed mice exhibited increased energy intake and became obese and hyperglycemic. Adipocyte diameter increased in female SUCR‐fed mice compared to TAG and CONTROL. Male and female SUCR‐fed mice had increased serum cholesterol and triglyceride concentrations compared to TAG and CONTROL. Atherosclerosis was increased in SUCR‐fed mice of both genders compared to TAG and CONTROL. Lesions from SUCR‐fed mice exhibited pronounced macrophage immunostaining and reductions in collagen content compared to TAG and CONTROL mice. These results demonstrate that in comparison to sucrose, equivalent substitution of TAG as dietary carbohydrate does not result in the same extent of obesity, hyperglycemia, hyperlipidemia, and atherosclerosis.     

Variations in dietary triacylglycerol saturation alter the lipid composition and fluidity of rat intestinal plasma membranes

Rats were maintained on nutritionally complete diets enriched in unsaturated (corn oil) or saturated (butter fat) triacylglycerols. After 6 weeks, significant differences in the lipid composition and fluidity of a number of intestinal membranes were observed. The corn oil diet (enriched mainly in linoleic acid) increased the overall unsaturation of the acyl chains and enhanced the lipid fluidity, as assessed by the fluorescence anisotropy of 1,6-diphenyl-1,3,5-hexatriene, of enterocyte microvillus and basolateral membranes and of colonocyte basolateral membranes. Concomitantly, the cholesterol content and the cholesterol/phospholipid molar ratio were increased in the microvillus but not in the basolateral membranes. The increased cholesterol in ileal microvillus membranes can result from enhanced cellular biosynthesis, since ileal slices from rats fed the unsaturated diet incorporated [14C]octanoate more rapidly into digitonin-precipitable sterol. Increased fluidity of the enterocyte microvillus and basolateral membranes, respectively, enhanced the enzyme specific activities of p-nitrophenylphosphatase and (Na+ + K+)-dependent adenosine triphosphatase. The results indicate that the lipid composition, fluidity and enzyme activities of intestinal plasma membranes can be altered by dietary means. Moreover, rat enterocytes possess regulatory mechanisms which modulate the cholesterol content of the microvillus membranes so as to mitigate changes in lipid fluidity.     

Propranolol,a β-adrenergic antagonist,attenuates the decrease in trabecular bone mass in high calorie diet fed growing mice

We investigated the effects of high calorie and low calorie diets on skeletal integrity, and whether β-adrenergic blockade (BB) attenuates bone loss induced by dietary calorie alteration. Male 6-week-old C57BL/6 mice were assigned to either an ad-lib fed control diet (CON), a high calorie diet (HIGH), or a low calorie diet (LOW) group. In each diet group, mice were treated with either vehicle (VEH) or propranolol, a β-adrenergic antagonist. Over 12-weeks, β-blockade mitigated body weight and fat mass increases induced by the high calorie diet. Femoral trabecular bone mineral density and the expression levels of osteogenic marker genes in bone marrow cells were reduced in HIGHVEH and LOWVEH mice, and BB significantly attenuated this decline only in HIGH mice. In summary, the magnitude of bone loss induced by low calorie diet was greater than that caused by high calorie diet in growing mice, and β-blockade mitigated high calorie diet-induced bone loss. [BMB Reports 2014; 47(9): 506-511]     

Long-Term Low Carbohydrate Diet Leads to Deleterious Metabolic Manifestations in Diabetic Mice

We investigated long-term effects of low carbohydrate diets on wild type mice, streptozotocin-injected and KKAy obese diabetic mice. These mice were pair-fed three different types of diets, standard chow (SC, C∶P∶F = 63∶15∶22), a low carbohydrate (LC, C∶P∶F = 38∶25∶37) diet and a severely carbohydrate restricted (SR, C∶P∶F = 18∶45∶37) diet for 16 weeks. Despite comparable body weights and serum lipid profiles, wild type and diabetic mice fed the low carbohydrate diets exhibited lower insulin sensitivity and this reduction was dependent on the amount of carbohydrate in the diet. When serum fatty acid compositions were investigated, monounsaturation capacity, i.e. C16:1/C16:0 and C18:1/C18:0, was impaired in all murine models fed the low carbohydrate diets, consistent with the decreased expression of hepatic stearoyl-CoA desaturase-1 (SCD1). Interestingly, both the hepatic expressions and serum levels of fibroblast growth factor 21 (FGF21), which might be related to longevity, were markedly decreased in both wild type and KKAy mice fed the SR diet. Taking into consideration that fat compositions did not differ between the LC and SR diets, we conclude that low carbohydrate diets have deleterious metabolic effects in both wild type and diabetic mice, which may explain the association between diets relatively low in carbohydrate and the elevated risk of cardiovascular events observed in clinical studies.     

Isocaloric manipulation of macronutrients within a high-carbohydrate/moderate-fat diet induces unique effects on hepatic lipogenesis,steatosis and liver injury

Diets containing excess carbohydrate and fat promote hepatic steatosis and steatohepatitis in mice. Little is known, however, about the impact of specific carbohydrate/fat combinations on liver outcome. This study was designed to determine whether high-energy diets with identical caloric density but different carbohydrate and fat composition have unique effects on the liver. Four experimental diets were formulated with 60% kcal carbohydrate and 20% kcal fat, each in nearly pure form from a single source: starch-oleate, starch-palmitate, sucrose-oleate and sucrose-palmitate. The diets were fed to mice for 3 or 12 weeks for analysis of lipid metabolism and liver injury. All mice developed hepatic steatosis over 12 weeks, but mice fed the sucrose-palmitate diet accumulated more hepatic lipid than those in the other three experimental groups. The exaggerated lipid accumulation in sucrose-palmitate-fed mice was attributable to a disproportionate rise in hepatic de novo lipogenesis. These mice accrued more hepatic palmitate and exhibited more evidence of liver injury than any of the other experimental groups. Interestingly, lipogenic gene expression in mice fed the custom diets did not correlate with actual de novo lipogenesis. In addition, de novo lipogenesis rose in all mice between 3 and 12 weeks, without feedback inhibition from hepatic steatosis. The pairing of simple sugar (sucrose) and saturated fat (palmitate) in a high-carbohydrate/moderate-fat diet induces more de novo lipogenesis and liver injury than other carbohydrate/fat combinations. Diet-induced liver injury correlates positively with hepatic de novo lipogenesis and is not predictable by isolated analysis of lipogenic gene expression.     

Feeding rats a high fat/carbohydrate ratio diet reduces jejunal S/I activity ratio and unsialylated galactose on glycosylated chain of S–I complex

AimsWe examined whether decreasing jejunal sucrase/isomaltase (S/I) activity ratio by feeding rats a high fat/carbohydrate ratio diet is regulated by changing glycosylated chains on the S–I complex.Main methodsJejunal activities of sucrase, isomaltase and β-1,4-galactosyltransferase were examined in rats fed a high fat/carbohydrate or a low fat/carbohydrate ratio diet. The amount of galactose and mannose in the glycosylated chain on the S–I complex in rats fed both diets was determined using RCA₁₂₀ and Con A lectins, respectively. The effects of reducing unsialylated galactose from the glycosylated chain on the S–I complex were assessed by determining sucrase activity in purified S–I complex treated with β-galactosidase.Key findings and significanceFeeding rats a high fat/carbohydrate ratio diet reduced jejunal S/I activity ratio in mucosal homogenates and purified fractions. The level of unsialylated galactose in glycosylated chains on the S–I complex was reduced by feeding rats a high fat/carbohydrate ratio diet. The form with reduced levels of unsialylated galactose had lower sucrase activity than that with more unsialylated galactose. The reduction of galactose on the S–I complex by β-galactosidase in vitro reduced sucrase activity. Feeding rats a high fat/carbohydrate ratio diet also reduced jejunal β-1,4-galactosyltransferase activity. Taken together, decreasing the S/I activity ratio by feeding rats a high fat/carbohydrate diet is associated with the reduction of unsialylated galactose on the glycosylated chain of the S–I complex.     

Change of the Gluconeogenic Capacity of Rat Kidney Cortex Slices with Dietary Components

Substituting protein for carbohydrate in diets significantly enhanced the rates of glucose formation from pyruvate, glutamate, or glycerol in rat kidney cortex slices. The tissue, however, increased slightly its gluconeogenic capacity in response to low carbohydrate, high fat diet. The rates of glucose taken up per unit weight of kidney cortex of rats fed a high carbohydrate diet was higher than those of rats fed diets high in protein or fat. Kidney weight in g per 100 g body weight (relative kidney size) of rats fed diets high in protein was significantly higher than that of rats fed diets high in carbohydrate or fat.     

Parental spleen cells accelerate the development of intestinal brush border structure and function in neonatal mice

The influence of parental spleen cells on the postnatal development of brush border microvillus membrane structure and the ability to transport lysine and alanine has been studied in the mouse jejunum during the second week of postnatal life. Control tissue taken from 7-11 day old mice has an unchanging crypt-villus structure and a low enterocyte migration rate of about 1 micron hr-1. Microvillus elongation in crypt enterocytes takes 6 days to complete under these conditions. Lysine and alanine transport begin 2 days after structural differentiation has ceased. Parental spleen cells injected into 1-2-day-old F1 mice cause crypt cell hyperplasia, villus shortening and a 3-6-fold increase in enterocyte migration rate after a period of 8 days. These effects are associated with large reductions in the time needed to complete microvillus membrane development and first express absorptive function. Lysine and alanine transport begin approximately 6 hr after structural differentiation has ceased under these conditions. Adaptive changes in the development of enterocyte structure and function, induced by injection of parental spleen cells, bear some resemblance to other changes found to occur normally at weaning and in adult animals subjected to controlled changes in diet and environmental temperature. The possibility that common principles govern enterocyte adaptation and that some of these still apply in an intestine undergoing an immune reaction is discussed.     

Testing the hypothesis that crypt size determines the rate of enterocyte development in neonatal mice

Pieces of mid-jejunum taken from 7-9 day old mice have been used to determine microvillus length in enterocytes located at different points along the crypt-villus axis to test the hypothesis that enterocyte development of structure is directly determined by the physical characteristics of the intestinal crypt. Parallel measurements of enterocyte migration rate were carried out using tritiated thymidine to determine the time course of microvillus elongation in neonatal mice. Microvillus length approximately doubled during early enterocyte migration from the crypt base to the lower part of the villus. Enterocyte migration rate was only 0.9 micron/hr at this stage of development, a value considerably less than that found in adult intestine. Results plotting the time dependency of microvillus elongation were fitted by a logistic curve giving a maximal rate for microvillus growth of 0.004 micron/hr. The corresponding estimate of crypt depth was 35 microns. Both these values are considerably less than those found in adult intestine. These results provide strong support for the general hypothesis that some factor associated with the physical length of the crypt, called crypt factor or CF, is directly responsible for controlling the way enterocytes organize subsequent structural differentiation of their surface membranes.     

Dietary carbohydrate type and cholesterol-induced hypercholesterolemia in cynomolgus monkeys: influence of oral antibiotic

The relationship of carbohydrate type to cholesterol-induced hypercholesterolemia and the potential role of intestinal flora in the above process were examined in 12 male cynomolgus monkeys (M. fascicularis). Semipurified diets provided two types of carbohydrates (starch or sucrose, 49% by calorie) with 0.4 mg cholesterol/kcal. Six weeks of the starch diet resulted in significantly enhanced hypercholesterolemia when compared to sucrose diet. Starch in relation to sucrose produced cholesterol enrichment of intermediate density lipoproteins and increase in low density lipoprotein particles, whereas sucrose increased high density lipoprotein constituents (phospholipids, cholesterol, and apoA-I) and triglyceride content of very low density lipoproteins. Fecal Escherichia counts were high during the starch diet as contrasted with sucrose diet, but the Escherichia, Streptococcus, and Bacteroides groups did not show differences by diet following each consecutive 4-week period of oral neomycin (107 mg/kg body wt) treatment and withdrawal. The magnitude of hypercholesterolemia during these periods also remained similar between starch and sucrose, suggesting formation of germfree metabolic characteristics. Thus, the magnitude of cholesterol-induced hypercholesterolemia can be affected by the type of carbohydrate, which may be in part determined by intestinal flora metabolism.     

Effect of iron status on DMT1 expression in duodenal enterocytes from beta2-microglobulin knockout mice

Divalent metal transporter I (DMT1) is thought to be involved in transport of iron across the apical cell membrane of villus duodenal cells. To determine its role in hereditary hemochromatosis (HH), we used beta2-microglobulin knockout (B2M-/-) mice that accumulate iron as in HH. The B2M-/- and control C57BL/6 (B2M+/+) mice were fed diets with different iron contents. Increasing the iron availability increased plasma iron levels in both B2M+/+ and B2M-/- mice. Reducing the iron availability decreased the plasma iron concentration in B2M+/+ mice but was without effect on plasma iron in B2M-/- mice. DMT1 was not detectable in mice fed normal or iron-loaded diets when using immunohistochemistry. In Western blots, however, the protein was consistently observed regardless of the dietary regimen. DMT1 expression was increased to the same extent in B2M+/+ and B2M-/- mice when fed an iron-poor diet. In both strains of mice fed an iron-poor diet, DMT1 was evenly distributed in the differentiated enterocytes from the base to the tip of the villi but was absent from the crypts of Lieberkühn. These data suggest that the observed effects were due to the state of iron deficiency in mucosal cells rather than genetic defect.     

Effect of a moderate variation in dietary energy intake on the retention and excretion of zinc,calcium, and magnesium

Mineral balance was studied by metabolic balance techniques in 13 healthy college females aged 21–23 yr. They were fed diet containing 1780 kcal, 2580 kcal, and 25 g protein in a 20-d experiment period. Both diets contained approximately 5.28 mg zinc, 216.85 mg calcium, and 364.3 mg magnesium. The diet consisted of habitually consumed foods. Blood, urine and fecal samples were collected for mineral analysis using atomic absorption spectrophotometry. Plasma mineral levels were not affected by the change in dietary energy intake. Fecal calcium and magnesium were significantly higher when subjects were fed the low calorie (1780 kcal) diet, whereas there was no significant difference in fecal zinc for the two levels of dietary energy. Urinary calcium and magnesium were also significantly higher when the diet provided 1780 kcal though, on the other hand, urinary zinc was significantly higher when the diet provided 2680 kcal (P<0.05). Urinary calcium and magnesium correlated negatively, whereas urinary zinc correlated positively, with the dietary energy intake (P ^o<0.05). Dietary energy intake has a significant effect on the mineral balance of the subjects.     

Effect of the energy density of non-purified diets on reproduction, obesity, alopecia and aging in mice.

Four diets with graded levels of energy at 24% crude protein were fed to C57BL/6J mice for approximately 3 years to develop pelleted non-purified diets. The nitrogen-corrected metabolizable energy (MEn) of the diets ranged from 2.86 to 3.73 kcal per g of dry matter (DM). Fifteen males and 30 females were assigned to each diet. The mice were housed together for 1 week at 7 week intervals, experiencing 5 matings. After the reproduction stage, they were allowed to complete their life span. Moribund mice after 60 weeks of age were subjected to histopathological examination. The highest energy diet showed the following results in comparison with the lowest energy diet: (1) weaning weight of pups increased by 31.6%; (2) males showed slight obesity even during the reproduction stage, but females did not; (3) both sexes developed remarkable obesity after 50 weeks of age with 41.2% (males) and 49.6% (females) increasing in maximum body weight; (4) although daily feed intake decreased by approximately 18%, the MEn was slightly over consumed; (5) females showed higher incidence of alopecia with age; (6) the survival rate after 50 weeks of age decreased earlier and life span was shortened; (7) histopathological changes associated with aging developed earlier. On the other hand, the early death rate of dams at parturition increased with a decrease in dietary energy. It was concluded that at least 2 types of diets are needed throughout the life span of C57BL/6J mice; a high energy diet with an MEn value of 3.73 kcal/g DM for maximum reproduction and a low energy diet with an MEn value of 2.86 kcal/g DM for the long term stage after reproduction to retard obesity and aging most effectively.     

Influence of malnutrition and alterations in dietary protein on murine rotaviral disease

The possible correlation between malnutrition and degree of severity of rotavirus-associated infantile diarrhea which appears to occur in human populations was studied using a mouse model. To determine the effects of general malnutrition or altered levels of dietary protein, female mice were fed throughout pregnancy and infection periods with diets diluted with 0, 300, or 600 g glucose/kg, designated as normal nutrient to calorie ratio (N/C) diet, 70% N/C diet, or 40% N/C diet or with diets containing 75, 150, or 300 g casein/kg, as low-, normal-, or high-protein diets. Murine rotavirus was given by gavage to the 2-day-old offspring of these dams, and the extent of infection determined. Marked increases in severity of diarrheal disease were seen in the infants from dams receiving the 40 and 70% N/C diets and the low-protein diet. Severity of infection was seen as increased deaths, reduced weight gain, and increased passage of diarrheic feces. Intestinal viral levels and intestinal diarrhea scores did not vary appreciably. Serum interferon remained below detectable limits throughout the studies, but serum antibody was determined in dams 30 days post-virus exposure. The latter titers were lower in the infected mice from dams fed the 40 and 70% N/C diets, but were essentially the same in all the protein diet groups. Cross-fostering was done using the 40 and 100% N/C diets, wherein mice from dams fed either diet were placed on mothers fed the opposite diet. Increased severity of infection was again seen when the virus was given 2 days after the exchange, although the greatest infection occurred in animals from dams fed 40% N/C diet which were then fostered by other similarly fed dams. The increased host sensitivity to the rotaviral infection appeared to be a result of both pre- and postnatal dietary effects.     

Effect of the energy density of non-purified diets on growth, gestation and lactation in mice

The effects of dietary energy density on the performance of growing, gestating and lactating C57BL/6J mice were determined in order to develop pelleted non-purified practical diets for use in all stages of the mouse life cycle. Experimental diets with 4 levels of energy at 24% crude protein (CP) were pelleted and the nutritional values were determined using adult rats. The nitrogen-corrected metabolizable energy (MEn) values ranged from 2.86 to 3.73 kcal/g and the digestive CP (DCP) contents ranged from 20.5 to 22.6% on a dry matter (DM) basis. Mice responded to decreased dietary energy by increasing their feed intake to maintain MEn intake levels, except for 1 week after weaning and during lactation periods. During these periods, mice fed lower energy diets could not consume as much MEn as those fed higher energy diets. The lowest energy diet, in comparison with the highest energy diet, resulted in approximately a 33% lower weaning weight of pups at 3 weeks of age, a 13.2 to 34.4% slower growth at 3 to 4 weeks of age, and a 9.3 day delay in the onset of vaginal opening in young females. Lower energy diets, however, did not affect the litter size or the birth weight of pups. The DCP intake usually increased with decreases in dietary energy but apparently this did not affect the performance of the mice. It was concluded that an optimal diet should have an MEn value of 3.73 kcal/g DM or more for both the one week post weaning growth period and during lactation, but a diet with an MEn value of 2.86 kcal/g DM was sufficient for growth after 4 weeks of age and during gestation.