A review of body composition studies with emphasis on total body water and fat.

Tritiated water meausres a volume 4 to 15% body weight larger than that by desiccation, and, at present, only 0.5 to 2.0% of the overestimation can be explained by the exchange of hydrogen of tritiated water with those of the proteins and carbohydrates of the body. The remainder of the error is unexplained. Water in the lumen of the gut is an appreciable percentage of total body water (TBW) in many mammalian species, with the pig and the human as possible exceptions, and it should be considered an integral part of TBW. Consequently, the exclusion or inclusion of this transcellular water as part of TBW significantly affects the final TBW volume. As tritiated water exchanges with water in the gut, a comparison of the data from the indirect method with the data from the direct method can only be made when water in the gut is included in the desiccation method. Conceptually, the amount of water in lean body mass is a reflection of the actively metabolizing cell mass of the body. However, water in the gut is outside this cell mass, and if included, it significantly overestimates the water associated with the lean body mass compartment. The percentage of water in fat-free wet weight for most mature animals is estimated at 73.2%, although the mean values in the literature range from 63% for the beagle to 80% for the mouse, with the mean for the majority of species between 70 and 76%. If the percentage of water in fat-free wet weight lies between 70 and 76% for most species, then the error in calculating fat using the figure 73.2% in the equation (% fat = 100 - % TBW/0.732) is significant. In the application of this equation, the largest potential error lies in the estimation of TBW with tritiated water.

Calcium and phosphorus deficiencies affect mineral distribution in neonatal miniature piglets.

Current efforts to monitor the mineral status of preterm infants fed human milk may not provide sufficient information on the distribution of body minerals. To investigate the body distribution of calcium and phosphorus during various degrees of mineral deficiency, neonatal miniature piglets were raised for 2 wk on diets differing only in calcium and phosphorus. Groups A, B, and C were fed 100%, 60%, and 20%, respectively, of the recommended amounts of calcium and phosphorus that, when adjusted for rates of growth, approximated the range of dietary intakes of preterm infants. Group C manifested biochemical and body-composition evidence of mineral deficiency when compared with group A: lower serum phosphorus; higher serum alkaline phosphatase activity; less fat-free tissue, calcium, and phosphorus in tibiae, vertebrae, and whole carcasses. Neonatal miniature piglets are useful for studying mineral deposition during mineral deficiency in preterm infants.

Lean body mass of well-nourished women is preserved during lactation.

To determine whether the lean body mass of well-nourished women was mobilized to support milk protein output during lactation, the body composition of 10 lactating and 10 nonlactating women was examined longitudinally at 6-wk intervals between 6 and 24 wk postpartum and at 52 wk postpartum, and that of 10 nulliparous women was examined at equivalent intervals, by using clinical anthropometry and whole-body potassium counting. Milk production was determined at 6-wk intervals during the period of exclusive breast-feeding (6-24 wk postpartum) by the test-weighing procedure. Milk composition was determined by chemical analysis. Dietary intakes were determined at 6-wk intervals between 6 and 24 wk postpartum from 3-d food records with use of a nutrient database. Lean body mass was maintained in women who exclusively breast-fed their infants during the first 6 mo postpartum while consuming dietary protein in amounts that exceeded those of their nonlactating counterparts by 55%. The high protein intakes were sustained throughout lactation despite a progressive reduction by 32% of milk protein output. Lean body mass was preserved throughout lactation in well-nourished women, suggesting that the metabolic needs of milk protein production were met solely by higher protein intakes of the lactating women.

Reliability of fat-free mass estimates derived from total-body electrical conductivity measurements as influenced by changes in extracellular fluid volume.

Our study addresses the concern that the relationship between total-body electrical conductivity (TOBEC) measurements and the fat-free mass (FFM) or total-body water (TBW) of an individual is altered if significant fluid and electrolyte changes occur. Body composition and TOBEC measurements were obtained from 11 healthy miniature piglets before and after an intraperitoneal injection of physiological saline. The procedure expanded the extracellular fluid (ECF) volume by 11.8-34.1%, which represented an average increase in TBW of 7.9%. The linear regressions that related the preinjection and postinjection estimates of TBW or FFM to the corresponding transformed TOBEC signals were the same. Thus, the prediction equations derived for the untreated piglets accurately predicted both TBW and FFM in the piglets whose volume was expanded. These data suggest that prediction equations derived from healthy subjects should be equally valid for subjects with altered fluid status.

Total body water estimated by measuring total-body electrical conductivity.

A second-generation total-body electrical conductivity (TOBEC) instrument for adults (HA-2) was evaluated against isotope dilution of 2H and 18O for its ability to estimate total body water (TBW) in 20 healthy adults. The highest correlation coefficient (0.997) and the lowest standard error of the estimate (0.68 kg) were obtained using the first (FC0) and third (FC2) Fourier coefficients of the transformed TOBEC signals and the variables height (m) times average lean circumference (m) and age (y) in the prediction equation of TBW as follows: TBW (H218O) in kg = 10.8 + (0.0724.FC0) - (0.221.FC2) + (0.0398.age) + (9.2.height.average lean circumference) where average lean circumference is the average of the lean chest, abdomen, and thigh circumferences. The TOBEC instrument for adults provides a suitable alternative for the estimation of TBW.

Measurement of extracellular water volume by bromide ion chromatography.

Extracellular body water can be determined from plasma bromide dilution. Plasma Br is separated from other anions by ion chromatography and is detected at an ultraviolet wavelength of 210 nm. Plasma proteins are removed by ultrafiltration, and interference by plasma chloride is minimized by dilution and the use of 5 mmol NaCl/L as the eluant. Human plasma samples were spiked with known quantities of Br (between 37.54 and 125.14 mumol/L) and were measured by ion chromatography. The results were reproducible to within 0.72 mumol/L (SD) and differed from the gravimetric values by -1.88 +/- 4.27 mumol/L (mean +/- SD). The difference, however, was not significantly different from 0 (p = 0.19). Extracellular water volumes of 10 newborn minipigs measured by Br dilution by using the chromatographic technique (400 +/- 63 mL/kg) were comparable with literature values reported for premature infants.

The effects of different total parenteral nutrition fuel mixes on skeletal muscle composition of infant miniature pigs.

Two groups of 10-day-old miniature pigs were maintained on isocaloric and isonitrogenous total parenteral nutrition (TPN) regimens for nine days. One group received nonprotein energy as glucose, whereas the second group received a mixture of fat and glucose. The administration of the amino acid/glucose fuel mix resulted in higher plasma insulin but lower glucagon concentrations compared to the amino acid/glucose/fat mix. Differences also were observed in the composition of skeletal muscle, which contained higher concentrations of alkali-soluble (AS) proteins (chiefly cellular protein) and DNA, when glucose was the only source of nonprotein energy. Intracellular sodium and water content and nonalkali-soluble proteins (largely extracellular proteins) were lower in the skeletal muscle of the amino acid/glucose group than in that of the group receiving the fat regimen. No differences in RNA concentration, RNA/AS protein, or AS protein/DNA ratios were observed. These data suggest that conditions of high insulin production in the postnatal growth period favored increased DNA replication and accretion of AS protein. The differences in water and electrolyte composition indicate that the rate of chemical maturation of skeletal muscle was slower in the piglets receiving amino acids/glucose/fat than in those on the glucose regimen. This study has demonstrated that the source of nonprotein energy can influence skeletal muscle maturation in the postnatal period.

Tritiated water as a measure of body water in immature rats growing at different rates.

Rats were reared from birth in litters of 4, 10, and 16 to achieve different growth rates. Pups in the litters of 16 had no access to rat chow until days 21-28, when chow was made available to one of the litters to induce catch-up growth. Total body water was estimated by tritiated water (TBWHTO) on days 7, 14, 21, and 28 and then calculated from desiccation (TBWdes). TBWHTO was consistently larger than TBWdes for all groups. Differences were 10.9-16.9% on day 7 and 3.7-6.4% on day 28. On day 28, percent difference was higher in the slower-growing than the faster-growing groups. Nonaqueous hydrogen exchange was determined from tritium activity in the dried carcass. Less than 1% of the injected tritium exchanged with nonaqueous hydrogen during the equilibration period. Thus differences between TBWHTO and TBWdes in the younger animals could not be accounted for by nonaqueous hydrogen exchange but may have resulted from a larger loss of injected tritium, possibly in insensible water.

Electrolyte composition changes of chronically K-depleted rats after K loading.

The responses of whole body, skeletal muscle, and plasma to oral K loading were studied in K-depleted male rats. Potassium depletion was induced by feeding the rats a K-deficient diet for 4 wk and injecting deoxycorticosterone acetate during the first week. After 4 wk, the rats were growth retarded and hypokalemic (1.9 mmol/l plasma) and had low whole-body and muscle K content, 188 +/- 27 and 276 +/- 19 mmol/kg fat-free dried tissue (FFDT), respectively, compared with 296 +/- 10 and 454 +/- 13 mmol/kg FFDT for the control group. Sodium and water retention also occurred in the K-deficient group. After K depletion, the rats were divided into four groups and received either 0, 1, 2, or 3 intragastric doses of 10 mmol KCl/kg at 8-h intervals. The rats were killed 8 h after the last dose. Control rats were treated similarly. K-depleted and control rats responded differently to K loading. In the normal rats, plasma K remained at 5.0 +/- 0.5 mmol/l, muscle K increased to 502 +/- 24 mmol/kg, and muscle K/N ratio increased from 3.0 to 3.4 mmol/g. In the K-depleted rats, plasma K increased to 7.2 +/- 0.7 mmol/l, muscle K increased to 453 +/- 50 mmol/kg, and muscle K/N ratio increased from 1.8 to 3.1 mmol/g. These data indicate that the capacity of the muscles to accumulate K was impaired after severe K depletion and caused elevated plasma K levels when repletion was complete.

Hepatotoxicity of prenatal and postnatal exposure to nicotine in rat pups.

Prenatal and postnatal exposure to nicotine have been shown to affect developing tissues in growing animals. Rat pups were exposed to nicotine prenatally and/or postnatally for 10 days by feeding pregnant and lactating rat dams water containing 0, 54, or 108 microM of nicotine. Nicotine exposure did not affect either litter sizes or body weights at birth and at 10 days of age. Exposure to 108 microM of nicotine prenatally increased significantly the incidence of focal necrosis at birth, and the liver damage was still evident at 10 days of age even after the pups were allowed to suckle dams not exposed to any nicotine during the study period. Continuation of nicotine exposure postnatally increased the incidence and severity of focal and confluent necrosis. Postnatal exposure to 108 microM of nicotine to pups not previously exposed also increased the incidence of mild focal and confluent necrosis, although not significantly. Exposure to nicotine prenatally did not affect liver malondialdehyde (MDA) levels at birth. However, liver MDA was significantly lower in rat pups exposed to nicotine prenatally when they were 10 days of age irrespective of whether there were further exposure to nicotine postnatally. Reasons for the late onset of the low MDA levels need further investigation. Postnatal nicotine exposure to either 54 or 108 microM of nicotine to pups not previously exposed fails to affect liver MDA at 10 days of age. The significant decrease in hepatic superoxide dismutase (SOD) levels reflects those of hepatic injury, indicating the possibility of a nicotine-induced downregulation of SOD enzyme production.

Lactation increases prolactin receptor expression in spleen and thymus of rats.

Prolactin receptors (PRL-R) are widely expressed on cells of the immune system. During lactation, the increase in serum PRL levels may modify the gene expression of these receptors. Specific PRL binding sites and the expressions of both PRL-R-L and PRL-R-S forms in thymus and spleen of nulliparous control, 10-day postpartum lactating, and 10-day postpartum nonlactating rats were studied. A semi-quantitative RT-PCR technique was used to detect the PRL-R gene transcript in the tissues. Our results showed that specific PRL binding sites and PRL-R-L mRNA and PRL-R-S mRNA were present in the lymphoid tissues with the PRL-R-L mRNA predominant. Lactation markedly increased specific binding sites and PRL-R-L mRNA in both spleen and thymus and only PRL-R-S in spleen. No differences between nulliparous control and postpartum nonlactating rats were observed in any of the parameters measured. The parallel increase in specific PRL binding sites and PRL-R-L mRNA suggests that lactation up-regulates PRL-R expression in lymphoid tissues and may be beneficial to the maternal immune system.

Redistribution of cytochrome c is not an essential requirement in C2-ceramide induced apoptosis in HL-60 cells.

bcl-2 has been shown to enhance cell survival by inhibiting apoptosis. The present study investigates the potential role of bcl-2 on apoptosis in HL-60 cells induced by different agents. HL-60/bcl-2 and control HL-60/neo cells were obtained by transfection of bcl-2 cDNA or the neomycin-resistant gene, respectively. Staurosporine (STS) promoted DNA fragmentation dose-dependently in the 6 h exposure assay while C2-ceramide was relatively slow in the induction of apoptosis (approximately 40% after 24 h) and required higher concentrations (> 20 microM). Caspases inhibitors, Ac-YVAD-cmk (100 microM) and zVAD-fmk (20 microM) had no effect on DNA fragmentation themselves. However, they blocked C2-ceramide-induced caspase-3 cleavage and apoptosis, but not the release of cytochrome c from the mitochondria. In addition, we found that both Ac-YVAD-cmk and zVAD-fmk failed to protect STS-induced apoptosis in HL-60 cells. Overexpression of bcl-2 inhibited STS and C2-ceramide induced cytochrome c redistribution, caspase-3 activation and apoptosis. These results suggest a protective role of bcl-2 in the regulation of apoptosis and cytochrome c release is unlikely to be involved in the final common pathway in apoptosis.

bcl-2 protects HL-60 cells from apoptosis by stabilizing their intracellular calcium pools.

bcl-2 has been shown to enhance cell survival by inhibiting apoptosis induced under different circumstances. In this study we investigated the effects of bcl-2 overexpression on the homeostasis of subcellular organelles such as ER and mitochondria. In our study, HL-60/bcl-2 and control HL-60/neo cells were obtained by transfection of bcl-2 cDNA or the neomycin-resistant gene, respectively. Apoptosis was evaluated by both DNA fragmentation and flow cytometry qualitatively and quantitatively, and the intracellular calcium by Fura-2/AM. Thapsigargin (TG), a highly specific inhibitor of the ER-associated Ca2+ pump, and Br-A23187, a calcium ionophore, were used in this study. Our results showed that overexpression of bcl-2 significantly blocked TG- and Br-A23187-induced apoptosis in calcium containing buffer. Measurement of intracellular calcium showed that bcl-2 overexpression could reduce sustained elevation of cytosolic Ca2+ induced by these agents. However, in calcium-free medium, bcl-2 overexpression maintained Ca2+ uptake in ER of both TG- and Br-A23187-treated cells. Moreover, the depletion of Ca2+ by EGTA enhanced TG- and Br-A23187-induced apoptosis, and reduced the anti-apoptotic action of bcl-2, suggesting that cytosolic Ca2+ elevation may be required for optimal ER pool refilling. These findings suggest that bcl-2 facilitates and maintains the replenishment of Ca2+ in intracellular stores and, as a result, influences the intracellular calcium, thus protecting the cells from death. In addition, there were no cytochrome c release from mitochondria into the cytosol in TG- and Br-A23187- induced apoptosis, suggesting that cytochrome c release is not a universal phenomenon in the apoptotic process.

Telomerase activity is not related to apoptosis in leukemic cell lines.

Any deregulation of apoptosis or an escape from cellular senescence will drive the cells to neoplasia. It remains unclear whether there is a direct linkage between apoptosis and telomerase activity particularly in transformed cell lines. In the present study, we investigated the telomerase activities in three leukemic cell lines (HL-60, U937 and K562) after treating these cells with various doses of antitumor drugs, puromycin or actinomycin D (ActD). Our results showed that HL-60 cells underwent apoptosis rapidly when treated with either 20 microg/ml of puromycin or 5 microg/ml of Act D with more than 60% of the cells becoming apoptotic at 6 hrs and almost 100% at 12 hrs. But telomerase activity analyzed by TRAP assay in these apoptotic cells remained unchanged as compared with the untreated control cells suggesting that whether the cells were apoptotic or not, it had no effect on telomerase activity. However, if lower dosages of the drugs were used, that is, 0.5-1.5 microg/ml of puromycin or 0.01-0.5 microg/ml of Act D, a decrease in telomerase activity was observed at 24-48 hrs, and was completely undetectable at 72 hrs. This decrease in telomerase activity was dose- and time-dependent. The suppression of telomerase activity by low doses of these two drugs is probably due to the inhibitory effect of the drugs on protein translation or RNA transcription rather than direct inhibition of the telomerase activity. Flow cytometry analysis of the cell cycle of the drug-treated cells showed that these drugs unselectively induced apoptosis at all phases of the cell cycle and was unrelated to the changes in telomerase activity. Similar results were observed in U937 and K562 cells except that K562 cells underwent apoptosis more slowly than the former two cell lines.

Protective effect of polysaccharides-enriched fraction from Angelica sinensis on hepatic injury.

A polysaccharides-enriched fraction from the root of Angelica sinensis, which is known for its antiulcer action on the gastrointestinal tract, was isolated and studied for its hepato-protective effect in rodents. Intra-gastric administration of Angelica sinensis polysaccharides-enriched fraction (AP) at the doses of 50 or 75 mg/kg dose-dependently prevented liver toxicity induced by acetaminophen in mice but did not affect the serum acetaminophen concentration. It normalized the rises of serum alanine transferase (ALT) and hepatic nitric oxide synthase (NOS) activities and the decrease of glutathione level in the liver. It also reduced the hepatic malondialdehyde (MDA) concentration. The protective effect was less evident in the carbon tetrachloride (CCl4)-treated animals including mice and rats. In the rat the elevated serum ALT level was unaffected though the MDA level was similarly reduced by the higher dose of AP. In these animals, CCl4 increased the hepatic glutathione level instead while the NOS activity remained unchanged. These findings suggest that the pathogenic mechanisms of both acetaminophen and CCl4 are different. AP is more effective in the protection against liver damage induced by acetaminophen, which is associated with the glutathione depletion and nitric oxide synthase activation in the liver.

Liver composition and histology in growing infant miniature pigs given different total parenteral nutrition fuel mixes.

Although young infants are at greater risk for total parenteral nutrition (TPN)-related liver disease than adults, previous studies on the effect of the TPN energy source on the development of hepatic steatosis have been carried out in adult rats and adult humans. We studied the effect of a glucose and a glucose/fat TPN energy regimen on hepatic chemical composition and the development of steatosis in newborn miniature pigs. Twenty miniature pigs were randomized at 10 days of age to receive a TPN regimen which utilized either glucose (group A) or glucose/fat (group B) as the non-nitrogen energy source. After 8 days, blood was drawn for insulin, glucagon, SGPT, albumin, and bilirubin determinations. Samples of liver were obtained at 9 days. Plasma insulin levels were significantly higher and glucagon levels lower in group A piglets than in those in group B. Normal values were obtained for SGPT, albumin, and bilirubin, and no differences were found between groups. Chemical analysis of the livers revealed no differences between groups in the concentrations of glycogen, fat, protein, DNA, and RNA. Group A animals had significantly higher concentrations of water than group B (group A: 0.75 +/- 0.01 liter/kg; group B: 0.74 +/- 0.01; p less than 0.03). A significant correlation was found in group B between the plasma insulin/glucagon ratio and the hepatic glycogen concentration (r = 0.73, p less than 0.05). Group A animals had fat vacuoles in centrilobular hepatocytes, in contrast with group B animals who had visible fat only in Kupffer cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Body mass index is different in normal Chinese and Caucasian infants.

Body mass index (BMI) is one of the anthropometric measurements for assessing nutritional status, body composition and adiposity in children. Racial differences in BMI between black and white children and adolescents have been shown in several studies. The aim of this study was to determine whether an ethnic difference in BMI exists between Chinese and Caucasian children in the first two years of life. The BMI of Chinese and Caucasian infants was compared so as to assess the usefulness of the National Center for Health Statistics (NCHS) growth reference data in the assessment of nutritional status of Chinese children. Mean weight, length and BMI were compared between six cohorts of Chinese children and five cohorts of Caucasian children together with the NCHS growth reference data. The changes in the mean BMI curves during the first two years of life in the two ethnic groups were entirely different but the different cohorts in the same ethnic groups displayed a similar pattern of change with age. The difference in change in BMI in the Chinese cohorts was related to the difference in change in their mean weight as compared to the NCHS weight-for-age reference data. In contrast, the change in mean length of the well-nourished Hong Kong Chinese children in the present study followed the mean NCHS height-for-age values. The results of this study suggest that linear growth would be better for the assessment of health and nutrition in infancy and early childhood. If BMI and weight-for-height standards were to be used then an ethnic group-specific and population based reference data set should be used.

Total body water measurement by tritiated water in growing animals.

Data on 177 beagles were used to examine the hypothesis that the volume distribution of tritiated water (HTO) is significantly larger in some species of young growing animals than the volume of total body water (TBW) measured by desiccation in more mature animals. The beagles were divided into three groups. Group 1 consisted of 169 animals which ranged in age from 0 to 365 days and in weight from 0.25 to 13.5 kg. Group 2 consisted of 42 animals randomly selected from Group 1 over the entire age and weight range. Group 3 consisted of eight beagles which ranged in age from 2 to 5 years and in weight from 10.1 to 16.3 kg. Total body water was measured in Group 1 by HTO, in Group 2 by HTO and desiccation, and in Group 3 by HTO. The mean percentage difference between the measurements of TBW in Groups 1 and 2 increased between body weights of 0.2 to 3.4 kg (2 months old): in Group 1 from 14 to 28% and in Group 2 from 18 to 32%. From body weights of 4 to 13 kg, there was a progressive decrease in the mean difference between the two measures of TBW: in Group 1 from 28 to 4% and in Group 2 from 32 to 5%. Group 3 animals were a separate population statistically from other groups of beagles. At body weights of 12 and 13 kg, which overlapped with those of Group 2 dogs, there was no significant difference between the two measures of TBW. The present data support the proposed hypothesis.

Changes in water, protein, sodium, potassium, and chloride in tissues with growth of the beagle.

Changes in total body and tissue composition of 43 beagles were analyzed from 0 day (birth) to 1 year. The tissues studied were skeletal muscle, viscera (heart, lungs, gut, liver, kidneys), skeleton, skin, and brain, and the data were expressed as follows: fat-free tissue weight (FFTW) as a per cent of total fat-free wet weight (FFWW); water and protein in grams per kilogram FFTW; and Na, Cl, K in milliequivalents FFTW. The mass of skeletal muscle increased from 21% of FFWW at birth to 36% at 1 year while the contribution of the remainder of the tissues decreased: skeleton from 30 to 25%, viscera 23 to 15%, skin 18 to 13%, and brain 4 to 0.9%. Over the same period, total body water decreased from 780 g/kg to 665, water of skeletal muscle from 771 to 665, of viscera from 782 to 621, of skeleton from 644 to 424, of skin from 765 to 669, of brain from 853 to 692; Total protein increased from 113 g/kg to 196, in skeletal muscle from 122 to 253, in viscera from 114 to 195, in skeleton from 71 to 112, in skin from 170 to 227, and in brain from 63 to 164. Total Na was 84 mEq/kg throughout the first year of growth, 101 for skeleton, and 89 for skin, while Na increased in viscera from 66 to 75 and in brain from 63 to 77, but decreased in skeletal muscle from 75 to 59. Total K increased from 31 mEq/kg at birth to 62 at 1 year, and from 38 to 107 in skeletal muscle, from 49 to 78 in viscera, and decreased from 27 to 11 in skin, and 42 to 122 in brain. Total Cl decreased from 58 to 49, in skeletal muscle from 52 to 34, in skeleton from 43 to 33, while that in viscera increased from 56 to 78. The contribution of skeletal muscle and viscera (the major metabolic cell mass) to total FFWW increased from 44 to 52%, and it contributed over 50% of total water, protein, Cl, and 89% of K. Skeletal muscle accounted for the increases. Skin and skeleton contributed 38% of FFWW, 17% of water, 29% of Na, 19% of Cl, 16% of protein, and 10% of K. The rates of change in these parameters fell into three patterns: (1) the content of the chemical component did not change significanly in the first year of growth; (2) it increased or decreased at a constant rate; or (3) there were two rates at which the concentration changed; the break between them occurred between the third and fourth months and coincided with evidence of increasing sexual maturation. A specific pattern of change was characteristic of a particular tissue and appeared independent of that of the total dog and other tissues. These data support the conclusion that there are mechanisms intrinsic to each tissue which exert a degree of control during growth over its chemical composition; therefore, growth itself can be considered an intrinsic regulatory mechanism.

Perinatal feedings adversely affect lipogenic activities but not glucose handling in adult rats.

The long-term effects of early under- and overfeeding on glucose metabolism and fat cell lipogenesis were studied. Newborn rats were reared in litter sizes of four, 10, and 16 pups. The amount of milk intake per pup varied inversely with litter sizes. A subgroup of pups from each group was studied at age 20 d, whereas another subgroup was weaned to an ad libitum feeding of standard rat chow and studied at 12 wk of age. There were no differences among groups in food intake on the basis of per gram body weight. Overfeeding during suckling resulted in fatter rats at weaning and in the adults. The higher fat contents in the adipose tissues and carcasses were associated with higher fatty acid synthase and lipogenic activities in the adipose tissues at weaning and 12 wk of age. Differences in plasma insulin and glucose levels among groups were observed only in the 20-d-old rats: basal insulin and glucose levels and 30-min postglucose insulin levels were highest in the overnourished and lowest in the undernourished rats. However, by 12 wk of age, there were no significant differences among groups in their basal insulin and glucose levels and after an oral dose of glucose. Our results suggest that overfeeding or underfeeding during the suckling period affects the glucose-insulin axis only temporarily and not permanently, but early overfeeding permanently enhances fatty acid synthase and lipogenic activities in adipose tissues, resulting in fatter adult rats.