Preweaning food intake influences the adiposity of young adult baboons.

The hypothesis that preweaning nutrition influences adult fat cell number and adiposity was tested in baboons. Newborn baboons were fed Similac formulas with caloric densities of 40.5 kcal (underfed), 67.5 kcal (fed normally), and 94.5 kcal (overfed) per 100 g formula. From weaning (16 wk) until necropsy at 5 yr of age all baboons were fed the same diet. At necropsy, fat cell number and fat cell size in 10 fat depots were measured. Female baboons overfed as infants had markedly greater fat depot mass, primarily because of fat cell hypertrophy, than normally fed or underfed females. Overfed male baboons had a greater fat mass in 4 of 10 depots compared with males underfed or fed normally as infants. Underfeeding did not affect body weight, nor adipose mass of either sex. The results show that infant food intake does not have a major influence on the fat cell number of young adult baboons.

Mixed spermatogenic germ cell nuclear extracts exhibit high base excision repair activity.

Spermatogenic cells exhibit a lower spontaneous mutation frequency than somatic tissues in a lacI transgene and many base excision repair (BER) genes display the highest observed level of expression in the testis. In this study, uracil-DNA glycosylase-initiated BER activity was measured in nuclear extracts prepared from tissues obtained from each of three mouse strains. Extracts from mixed spermatogenic germ cells displayed the greatest activity followed by liver then brain for all three strains, and the activity for a given tissue was consistent among the three strains. Levels of various BER proteins were examined by western blot analyses and found to be consistent with activity levels. Nuclear extracts prepared from purified Sertoli cells, a somatic component of the seminiferous epithelium, exhibited significantly lower activity than mixed spermatogenic cell-type nuclear extracts, thereby suggesting that the high BER activity observed in mixed germ cell nuclear extracts was not a characteristic of all testicular cell types. Nuclear extracts from thymocytes and small intestines were assayed to assess activity in a mitotically active cell type and tissue. Overall, the order of tissues/cells exhibiting the greatest to lowest activity was mixed germ cells > Sertoli cells > thymocytes > small intestine > liver > brain.

Effects of dietary cholesterol and fat, sex and sire on lecithin-cholesterol acyltransferase activity in baboons.

We analyzed the effects of dietary cholesterol, type of dietary fat, sex and sire progeny family on lecithin-cholesterol acyltransferase activity in 80 adult baboons. The animals were the progeny of 80 dams and 6 sires and were randomly assigned at birth to breast feeding or to one of three formulas containing 0.02, 0.30 or 0.60 mg cholesterol/ml. After weaning at 4 months of age the animals were fed one of four diets that were either high or low in cholesterol with 40% of the calories from either saturated or unsaturated fat. The fractional and molar rates of lecithin-cholesterol acyltransferase activity were measured at 7-8 years of age by an HPLC method. Infant diet (breast vs. formula feeding or level of cholesterol in formula had no effect on enzyme activity later in life. The adult diets that were high in cholesterol decreased the fractional lecithin-cholesterol acyltransferase rate by 20% / compared to diets low in cholesterol (7.89 vs. 9.84%/h, P less than 0.002), but dietary cholesterol did not affect the molar activity. Animals fed the high cholesterol diets had higher unesterified cholesterol concentrations compared to those fed the low cholesterol diets (38.1 mg/dl vs. 31.6 mg/dl, P less than 0.0001). The molar lecithin-cholesterol acyltransferase rate was increased 13% by saturated compared to unsaturated fat (83.3 vs. 73.6 nmol/h per ml plasma, P less than 0.07), but no effect of dietary fat was observed on the fractional enzyme activity. Females compared to males had significantly higher fractional (10.9 vs. 7.14%/h, P less than 0.0001) and molar lecithin-cholesterol acyltransferase activities (99.3 vs. 61.7 nmol/h per ml plasma, P less than 0.0001). After adjustment for the effects of diet and sex we observed differences in the fractional activity (range, 7.2-10.8%/h, P less than 0.04) and in the molar rate (range, 63.6-99.8 nmol/h per ml plasma, P less than 0.07) among the six sire progeny groups. The differences among sire progeny groups are evidence for genetic differences in lecithin-cholesterol acyltransferase activities among the baboon families.

Influence of breast and formula feeding on hepatic concentrations of apolipoprotein and low-density lipoprotein receptor mRNAs.

We tested the hypothesis that breast and formula feeding differentially affect hepatic mRNA concentrations for LDL receptor (LDL-R) and apolipoproteins A-I, B and E in infant baboons during the preweaning period. The mRNA concentrations were measured in liver biopsies obtained prior to weaning at 14 weeks from 43 baboons that were either breast-fed (n = 17) or fed formulas with a high (n = 12) or low (n = 14) polyunsaturated/saturated (P:S) fat ratio. Breast-fed baboons had 99% higher LDL-R mRNA concentrations compared with infants fed formulas, but there were no differences among breast and formula-fed baboons in mRNA concentrations of apolipoproteins A-I, B or E. The fatty acid P:S ratio of the formulas did not affect hepatic LDL-R or apolipoprotein mRNA concentrations. These results suggest that breast-feeding increases LDL-R gene expression even though breast milk is higher in cholesterol and saturated fat compared with formulas.

Effects of nonlipid risk factors on atherosclerosis in youth with a favorable lipoprotein profile.

BACKGROUND: The strong association between coronary heart disease and dyslipoproteinemia has often overshadowed the effects of the nonlipid risk factors-smoking, hypertension, obesity, and diabetes and impaired glucose tolerance-and even led to questioning the importance of these risk factors in the presence of a favorable lipoprotein profile. METHODS AND RESULTS: A cooperative multicenter study, the Pathobiological Determinants of Atherosclerosis in Youth (PDAY), examined the relation of the nonlipid risk factors to atherosclerosis in 629 men and 227 women 15 to 34 years of age who died of external causes and who had a favorable lipoprotein profile (non-HDL cholesterol <4.14 mmol/L [<160 mg/dL] and HDL cholesterol >/=0.91 mmol/L [>/=35 mg/dL]). In the abdominal aorta, smokers had more extensive fatty streaks and raised lesions than nonsmokers, and hypertensive blacks had more raised lesions than normotensive blacks. In the right coronary artery, hypertensive blacks had more raised lesions than normotensive blacks, obese men (body mass index >/=30 kg/m(2)) had more extensive fatty streaks and raised lesions than nonobese men, and individuals with impaired glucose intolerance had more extensive fatty streaks. Obese men had more severe lesions (American Heart Association grade 2 through 5) of the left anterior descending coronary artery. CONCLUSIONS: These substantial effects of the nonlipid risk factors on the extent and severity of coronary and aortic atherosclerosis, even in the presence of a favorable lipoprotein profile, support the need to control all cardiovascular risk factors.

Association of Coronary Heart Disease Risk Factors with microscopic qualities of coronary atherosclerosis in youth.

BACKGROUND: This study examined whether atherosclerosis in young people is associated with the risk factors for clinical coronary heart disease (CHD). Methods and Results-Histological sections of left anterior descending coronary arteries (LADs) from 760 autopsied 15- to 34-year-old victims of accidents, homicides, and suicides were graded according to the American Heart Association (AHA) system and computerized morphometry. Risk factors (dyslipoproteinemia, smoking, hypertension, obesity, impaired glucose tolerance) were assessed by postmortem measurements. Approximately 2% of 15- to 19-year-old men and 20% of 30- to 34-year-old men had AHA grade 4 or 5 (advanced) lesions. No 15- to 19-year-old women had grade 4 or 5 lesions; 8% of 30- to 34-year-old women had such lesions. Approximately 19% of 30- to 34-year-old men and 8% of 30- to 34-year-old women had atherosclerotic stenosis > or =40% in the LAD. AHA grade 2 or 3 lesions (fatty streaks), grade 4 or 5 lesions, and stenosis > or =40% were associated with non-HDL cholesterol > or =4.14 mmol/L (160 mg/dL). AHA grade 2 or 3 lesions were associated with HDL cholesterol <0.91 mmol/L (35 mg/dL) and smoking. AHA grade 4 or 5 lesions were associated with obesity (body mass index > or =30 kg/m(2)) and hypertension (mean arterial pressure > or =110 mm Hg). CONCLUSIONS: -Young Americans have a high prevalence of advanced atherosclerotic coronary artery plaques with qualities indicating vulnerability to rupture. Early atherosclerosis is influenced by the risk factors for clinical CHD. Long-range prevention of CHD must begin in adolescence or young adulthood.

Rapid gastric emptying of a solid pancake meal in type II diabetic patients.

OBJECTIVE: To estimate the rate of gastric emptying of a solid pancake carbohydrate meal in recently diagnosed asymptomatic type II diabetic patients compared with nondiabetic control subjects. RESEARCH DESIGN AND METHODS: Gastric emptying studies using radiolabeled meals were performed on eight recently diagnosed asymptomatic diabetic patients and on eight sex-, BMI- and age-matched nondiabetic control subjects. Although a liquid protein drink was administered along with the pancake meal, the radioactivity was adherent to only the pancake portion of the meal. Plasma glucose and serum insulin levels were measured in fasting and postprandial blood samples collected at 15-min intervals up to 120 min after ingestion of the mixed nutrient meal. RESULTS: The average gastric half-emptying time (time it takes for one-half of the meal to empty) was significantly more rapid for the diabetic patients (45.3 +/- 4.8 min) when compared with the nondiabetic control subjects (60.4 +/- 5.1 min; P = 0.05). The serum insulin concentrations were not statistically different between the two groups. Plasma glucose values were significantly higher in the diabetic patients compared with the nondiabetic control subjects. CONCLUSIONS: Type II diabetic patients with no clinical evidence of neuronal dysfunction have a significantly more rapid rate of gastric emptying of a solid high-carbohydrate meal when compared with nondiabetic control subjects.

Effects of dietary cholesterol, type of fat, and sex on bile lipid composition of adult baboons.

We measured the effects of dietary cholesterol (0.24 vs 0.0024 mg/kJ), type of dietary fat [saturated, a ratio of polyunsaturated to saturated fatty acids (P:S) of 0.37, vs unsaturated (P:S of 2.2)], and sex on biliary lipid and bile acid conjugate composition of 80 adult pedigreed baboons. From these data we calculated the bile cholesterol saturation index and the bile acid hydrophobicity index. Dietary cholesterol significantly increased the bile cholesterol concentration by 25% and the bile cholesterol saturation index by 15%, but did not significantly affect the bile acid conjugate composition or the bile acid hydrophobicity index. Diets high in saturated fatty acid compared with unsaturated fatty acid significantly decreased the bile cholesterol concentrations by 26% and the saturation index by 23%. Saturated fatty acid also decreased the proportion of hydrophobic bile acids and lowered the bile hydrophobicity index. Male baboons had a higher cholesterol saturation index and a lower hydrophobicity index than females. Dietary cholesterol and saturated fatty acid independently influence the bile lipid composition and the cholesterol saturation index.

Dietary modulation of the progression of nephropathy in aging rats: an evaluation of the importance of protein.

Chronic nephropathy involving glomerular sclerosis markedly progresses in severity with age in male Fischer 344 rats fed ad libitum. Restricting food intake by 40% almost totally prevents progression of these lesions. Restricting food intake by 40% without restricting protein intake is also highly effective although somewhat less so than food restriction that includes protein restriction. These findings indicate that reducing the intake of protein is not the major reason for the retardation by food restriction of the age-associated progression of nephropathy in rats.

Origin of atherosclerosis in childhood and adolescence.

Atherosclerosis begins in childhood as deposits of cholesterol and its esters, referred to as fatty streaks, in the intima of large muscular arteries. In some persons and at certain arterial sites, more lipid accumulates and is covered by a fibromuscular cap to form a fibrous plaque. Further changes in fibrous plaques render them vulnerable to rupture, an event that precipitates occlusive thrombosis and clinically manifest disease (sudden cardiac death, myocardial infarction, stroke, or peripheral arterial disease). In adults, elevated non-HDL-cholesterol concentrations, low HDL-cholesterol concentrations, hypertension, smoking, diabetes, and obesity are associated with advanced atherosclerotic lesions and increased risk of clinically manifest atherosclerotic disease. Control of these risk factors is the major strategy for preventing atherosclerotic disease. To determine whether these risk factors also are associated with early atherosclerosis in young persons, we examined arteries and tissue from approximately 3000 autopsied persons aged 15-34 y who died of accidental injury, homicide, or suicide. The extent of both fatty streaks and raised lesions (fibrous plaques and other advanced lesions) in the right coronary artery and in the abdominal aorta was associated positively with non-HDL-cholesterol concentration, hypertension, impaired glucose tolerance, and obesity and associated negatively with HDL-cholesterol concentration. Atherosclerosis of the abdominal aorta also was associated positively with smoking. These observations indicate that long-range prevention of atherosclerosis and its sequelae by control of the risk factors for adult coronary artery disease should begin in adolescence and young adulthood.

Male rodent model of age-related bone loss in men.

Osteoporosis is a common occurrence in aging men. There is currently no appropriate animal model for studying age-related bone loss in men. To determine whether male Sprague-Dawley (SD) rats experience bone loss with aging and whether this rodent model is appropriate for studying age-related bone loss in men, SD rats aged 1-27 months were examined at the L-4 vertebra, the left femoral neck, and the left proximal tibia using peripheral quantitative computed tomography (pQCT) densitometry. In the L-4 vertebra of the male SD rats, cortical bone mineral content (BMC), cortical bone mineral density (BMD), and cortical bone thickness (Ct.Th) increased to a maximum at about 4 months of age and then plateaued. Vertebral cortical BMC began to decrease after about 13 months and vertebral Ct.Th began to decrease after about 9 months. By 27 months of age, vertebral cortical BMC decreased by 26.1% (p < 0.0001) and vertebral Ct.Th decreased by 31% (p < 0.0001). Vertebral cancellous BMC and vertebral cancellous BMD increased to a maximum at about 3 months of age and then declined progressively with aging after a short plateau. From 3 to 27 months of age, vertebral cancellous BMC and vertebral cancellous BMD had decreased linearly by 35.4% (p < 0.0001) and 49.4% (p < 0.0001), respectively. Both vertebral periosteal and vertebral endocortical perimeters of the L-4 vertebra of the rats increased with aging. From 9 to 27 months of age, the percent increase of vertebral endocortical perimeter (19.8%, p < 0.0001) was higher than that of vertebral periosteal perimeter (7.4%, p < 0.0001). This process was associated with a decrease with aging in vertebral Ct.Th. In addition, cancellous bone in the femoral neck and the proximal tibia began to be lost at 9 months of age and, by 27 months of age, cancellous BMC and cancellous BMD decreased by 59.7% (p < 0.0001) and 58.4% (p < 0.0001), respectively, in the femoral neck and by 72.2% (p < 0.0001) and 71.4% (p < 0.0001), respectively, in the proximal tibia. To gain further insight into the effects of aging on cancellous bone in the L-4 vertebra, histomorphometry was done on the L-4 vertebral body of animals aged 3, 6, 9, 18, and 24 months after pQCT densitometry. From 3 months of age and thereafter, cancellous bone volume (BV/TV) decreased progressively and, by 24 months, there was a decrease of 35.7% (p < 0.0001). In the L-4 vertebra, single- and double-labeled surfaces, mineral apposition rate (MAR), and bone formation rate (BFR/BS) decreased with aging. In conclusion, age-related bone loss in male SD rats started mostly from 9 months of age when bone growth had been completed. Aging male SD rats experience bone loss comparable to that seen in men. Thus, male SD rats represent an appropriate animal model of age-related bone loss in men. We recommend using male SD rats that are 9 months old as the starting age for age-related bone loss. We also suggest using the L-4 vertebra and femoral neck as the clinically relevant bone sites for determining the cause of the loss of bone, and how and whether therapeutic agents could modulate age-related bone loss in men.

Individual cigarette usage: self-reported data as a function of respondent-reported data.

The interview method was used to collect data from living respondent-subject pairs regarding cigarette usage of the subject; the nonsmoker subject was explicitly not studied. Several different measures of usage were tested. The mean correlation coefficient between subject-reported data and the corresponding respondent-reported data was 0.86; that is, at least 70% of the variability in subject-reported data can be accounted for from information obtained from an appropriate living respondent closely associated with the subject. Selected regression equations are presented for estimating cigarette usage of a subject from data provided by a respondent.

Influence of infant and juvenile diets on serum cholesterol, lipoprotein cholesterol, and apolipoprotein concentrations in juvenile baboons (Papio sp.).

The long-term effects of infant diet (breast milk or formula containing 2, 30, or 60 mg/dl cholesterol) and subsequent dietary cholesterol (1 mg/kcal) and fat (saturated or unsaturated) on serum lipid and apolipoprotein concentrations were estimated using 82 juvenile baboons 4-6 years of age. A significant interaction of infant diet (breast vs formula) with type of fat (saturated vs unsaturated) at 4-6 years of age was observed on HDL cholesterol and apolipoprotein A-I (apoA-I) concentrations. That is, animals breast-fed as infants had higher HDL cholesterol and apoA-I concentrations when fed unsaturated fat from weaning to 4-6 years of age than those fed saturated fat (77 vs 68 mg/dl). In contrast, animals fed formulas in infancy followed by a diet containing unsaturated fat had lower HDL cholesterol and apoA-I concentrations at 4-6 years of age than did those fed saturated fat (67 vs 78 mg/dl). However, breast feeding or feeding formulas containing various levels of cholesterol for 3 months during infancy did not result in statistically significant differences in total serum cholesterol, VLDL + LDL cholesterol and apolipoprotein B (apoB) concentrations. Dietary cholesterol after infancy significantly increased serum total cholesterol, VLDL + LDL and HDL cholesterol, apoA-I and apoB concentrations. All of these response variables also were higher in animals fed saturated fat compared to those fed unsaturated fat on the same level of cholesterol. At 4-6 years of age, regardless of diet, females had significantly higher serum VLDL + LDL cholesterol (57 vs 43 mg/dl) and apoB concentrations (39 vs 30 mg/dl) than did males.

Effects of dietary polyunsaturated and saturated fats on lipoproteins in the baboon.

The effects of 2 different dietary fats (40% of calories from corn oil or coconut oil), in the presence of high-dietary cholesterol (1.7 mg/kcal), on the lipoprotein profiles of baboons (Papio cynocephalus sp) were studied by analytic ultracentrifugation, gradient gel electrophoresis (GGE), and heparin-manganese chloride precipitation. Relative to the corn oil (polyunsaturated fat) diet, the coconut oil (saturated fat) diet significantly increased total serum cholesterol by 43% (P less than 0.001) by increasing non-precipitable cholesterol (HDL-C) 58% (P less than 0.001) and precipitable cholesterol (VLDL + LDL-C) 35% (P less than 0.001). Analytic ultracentrifugal observations indicated that the increase in HDL-C was due to considerable increases in both HDL-I (baboon HDL of size 100-125 A and hydrated density 1.063-1.120 g/ml) and F1.20 degrees 9-28 lipoproteins (material of size 125-220 A and hydrated density 1.03-1.08 g/ml, and containing HDL apolipoproteins and apo E). Concentrations of other HDL subpopulations were unaffected by the dietary saturated rat. The increase in VLDL + LDL-C was due to increased LDL (S degree F 5-12 lipoproteins) and, to some extent, F1.20 degrees 9-28 lipoproteins because the larger, faster floating subspecies of the F1.20 degrees 9-28 lipoproteins were precipitable by heparin-manganese. In contrast, saturated fat (relative to polyunsaturated fat) induced lower concentrations of IDL (SF degree 12-20) and VLDL (SF degree 20-100). Lipoprotein size distributions by GGE indicated 5 HDL subpopulations and 2 or more LDL subpopulations in the sera of most baboons. The type of dietary fat did not affect the particle size range of each of the the HDL or LDL subpopulations. The results indicate that dietary fat markedly modulates the distribution of cholesterol between apo A-I-containing (HDL and F1.20 degrees 9-28) and apo B-containing (IDL and VLDL) lipoproteins without altering the presence of subpopulations based on particle size.

Linear gastric emptying of hyperosmolar glucose solutions.

We performed a total of 12 gastric emptying studies on 6 normal subjects with a hyperosmolar (1.85 mol/l) 400-kcal glucose solution commonly used for diagnosing diabetes and a more dilute (0.62 mol/l) 200-kcal glucose solution. The gastric half-emptying time was greatly prolonged with both glucose solutions; 107 min for the (1.85 mol/l) 400-kcal glucose solution compared to 66 min for the more dilute (0.62 mol/l) 200-kcal glucose solution. Although the 200-kcal glucose solution contained one-half the amount of glucose (50 g) compared to the 400-kcal solution (100 g), the blood glucose values obtained during a 2-hr period were only slightly lower with the former solution. This study demonstrates significantly delayed gastric emptying of glucose solutions in normal subjects and a linear pattern of gastric emptying formerly associated only with solid meals.

Rapid gastric emptying of an oral glucose solution in type 2 diabetic patients.

Gastric emptying of a liquid glucose meal was measured with scintigraphic techniques in nine recently diagnosed Type 2 diabetic patients and nine sex- and age-matched nondiabetic control subjects. Seven of the nine Type 2 diabetic patients were receiving oral hypoglycemic therapy which was discontinued the evening prior to the study. The other two diabetic patients were taking no medication. The average gastric half-emptying time was 33.6 min (s.e.m. = 3.2) for the diabetic patients and 64.6 min (s.e.m. = 4.2) for the nondiabetic controls (p = 0.0005). These measurements indicate rapid gastric emptying in Type 2 diabetic patients which may contribute to worsening of glucose control in these patients.

Accelerated gastric emptying in hypertensive subjects.

UNLABELLED: The phenomenon of accelerated gastric emptying has been previously reported in two conditions that are considered to be part of the insulin-resistance syndrome: namely, noninsulin-dependent diabetes (NIDDM) and increased body mass index (BMI). No previous studies have assessed the rate of gastric emptying in patients with essential hypertension, another disease considered to be part of the insulin-resistance syndrome. METHODS: Scintigraphic gastric emptying studies were performed on nine hypertensive subjects and on nine sex-, age-, ethnicity and BMI-matched controls. RESULTS: Subjects with hypertension had significantly more rapid gastric half-emptying times (gastric T50) (40.0 +/- 6.9 min versus 56.6 +/- 3.7 min, p = 0.02) than controls. There was an inverse relationship between average glucose during the first 30 min and 60 min of the oral glucose tolerance test with the gastric half-emptying time (Spearman rank correlation coefficient rs = -0.64, p = 0.0045 and rs = -0.48, p = 0.0428, respectively). CONCLUSION: The occurrence of accelerated gastric emptying in hypertensive subjects, in addition to that previously reported in subjects with NIDDM or increased BMI, suggests the possibility that accelerated gastric emptying may be a common finding in insulin resistant states.

Determinants of atherosclerosis in the young. Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Research Group.

A multicenter cooperative study, Pathobiological Determinants of Atherosclerosis in Youth, examined the relation of the risk factors for adult coronary artery disease to atherosclerosis in nearly 3,000 persons, aged 15-34 years, who died from accidents, homicides, and suicides and were autopsied in forensic laboratories. Very-low-density lipoprotein (VLDL) plus low-density lipoprotein (LDL) cholesterol levels were positively, and high-density lipoprotein (HDL) cholesterol levels were negatively, associated with both fatty streaks and raised lesions in the aorta and right coronary artery, particularly after age 25. Elevated glycohemoglobin levels were associated with raised lesions throughout the 15-34-year age span. Body mass index was associated with both fatty streaks and raised lesions of the right coronary artery in men but not in women. Smoking was associated with a 3-fold increase in raised lesions of the abdominal aorta in the 25-34-year age group. Women lagged after men in the extent of raised lesions in the right coronary artery by about 5 years, but the effects of risk factors in women, except for adiposity, were similar to those in men. The risk factors for adult coronary artery disease accelerate atherogenesis in the teenage years and their effects are amplified in young adulthood, 20-30 years before coronary artery disease becomes clinically manifest. Long-range prevention of adult coronary artery disease will require control of the risk factors early in life.

Estimating and testing an index of responsiveness and the relationship of the index to power.

Responsiveness has been proposed as a criterion, in addition to reliability and validity, to evaluate instruments that measure quality of life or functional status. The responsiveness index measures the change in a quality of life score due to a treatment relative to the variability of changes in that score within a stable control group. We derive the expected value, variance and distribution of the responsiveness index and give a large sample distribution for comparing the responsiveness of two different instruments. We also give the relationship between the responsiveness index and the power of a test of treatment effect.

Early determinants of adult metabolic regulation: effects of infant nutrition on adult lipid and lipoprotein metabolism.

In a series of experiments over the past 20 years, we have demonstrated long-term deferred effects of infant nutrition, particularly breast- as compared with formula-feeding and overfeeding as compared with normal or underfeeding, on serum HDL-cholesterol concentrations, adiposity, and atherosclerosis in the baboon, a large nonhuman primate. Low HDL-cholesterol levels and obesity are associated with accelerated progression of atherosclerosis and with increased risk of coronary heart disease in humans. We have observed other deferred effects of infant nutrition on bile acid metabolism, enzyme activities, and water and electrolyte balance, some of which may be physiologically related to HDL-cholesterol levels or to adiposity. The occurrence of these deferred effects suggests that infant nutrition may program other metabolic systems for life, and that these effects may contribute to other chronic diseases of adults. Although our understanding of the mechanisms by which infant diet regimens affect adult metabolism is meager, it is important to identify these mechanisms because they are likely to provide valuable clues to the causes and ultimately may contribute to the long-range prevention of those diseases.