Effect of early nutrition on the development of rat epididymal fat pads: cellularity and metabolism.

The effect of infantile nutritional levels on adipose tissue cellularity and metabolism was studied in two groups of Sprague-Dawley rats. Caloric intake was varied during the suckling period by manipulating litter size immediately after birth; however, all animals had free access to food after weaning. The epididymal fat pads of animals raised in small litters were heavier than those of their paired siblings raised in large litters. Initially, the differences in pad weight were accounted for primarily by differences in total cell number; however, at 20 wk both cell number and cell size contributed equally. The rate of glucose incorporation into CO(2) and triglyceride during in vitro incubations was the same for both groups if expressed on a per cell basis; therefore total tissue incorporation was greater in animals with more cells. The results support the hypothesis that early nutritional experiences can effect permanent changes in the cell number and size of the epididymal fat depot and that total cell number is important in the total metabolism of this organ. These findings and the fact that extreme human obesity is accompanied by similar alterations in cellularity and metabolism indicate that early nutritional experiences should be studied further as a guide to the etiology of obesity in man.

The role of adipose cell size and adipose tissue insulin sensitivity in the carbohydrate intolerance of human obesity.

Glucose metabolism and insulin sensitivity of isolated human adipose tissue was studied as a function of adipose cell size and number. Glucose metabolism by these tissues was closely related to the number of cells in the fragment, irrespective of cell size. Adipose cells of obese individuals metabolized glucose to carbon dioxide and triglyceride at rates similar to adipose cells of nonobese subjects. In contrast, insulin responsiveness of adipose tissue was dependent upon adipose cell size. The larger its adipose cells the less insulin sensitive was the tissue. Thus, adipose tissue of obese subjects, with enlarged cells, showed a diminished response to insulin. After weight loss and reduction in adipose cell size, insulin sensitivity of the adipose tissue of obese patients was restored to normal. When adipose tissue of obese individuals showed impaired responsiveness to insulin, their plasma insulin levels, after oral glucose, were elevated. Weight loss and reduction in adipose cell size restored plasma insulin concentration to normal, concomitant with the return of normal tissue insulin sensitivity.

The growth of adipose tissue in children and adolescents. Cross-sectional and longitudinal studies of adipose cell number and size.

Adipocyte size and number were determined in 288 subjects ranging in age from 4 mo to 19 yr. The study was performed in 110 obese and 178 non-obese subjects. 4-yr, longitudinal, follow-up studies were also performed in 132 subjects. The results demonstrate that the contribution of cell number and size to the growth of the fat depot in nonobese children varies with age. Deviations from this normal development were observed in obese children shortly after 1 yr of age. By 11 yr of age obese children exceeded the mean cell number found in nonobese adults. Indeed, obese subjects displayed more rapid and earlier elevations in both cell number and size, which were maintained throughout the study. Thus obese children display both quantitative and qualitative differences in fat tissue development when compared to nonobese children. The data indicate that the rate and type of adipose tissue cellular development one encounters in children may play a role in the development of the enlarged fat depots found in obese subjects.

Blood pressure, body composition, and fat tissue cellularity in adults.

While total body mass has been recognized for many years as having a strong positive association with blood pressure, it is not known whether body mass per se is important in this association or if a component of total mass, such as lean body mass or total body fat, is responsible for the relationship. To determine the relative importance of these components, 217 healthy adults unselected with respect to blood pressure or body composition, who were 18 to 49 years of age (X +/- sd = 33.1 +/- 8.9 years) had body density measured by underwater weighing. Body density was used to estimate percent body fat from which lean body mass and total body fat mass were determined. In addition, an adipose tissue biopsy from the gluteal area was made, and average fat cell size was measured using the osmium tetroxide method; fat cell number was then estimated. In both males and females, after adjusting for age, there were highly significant, positive partial correlations (r = 0.2 to 0.3) between measures of blood pressure (systolic, diastolic, and mean arterial) and percent body fat, total body fat mass or fat cell number. No significant correlation existed between lean body mass or fat cell size and any measure of blood pressure. These findings suggest that fat mass as opposed to body mass, per se, may be an important etiological component in elevated blood pressure in adults.

Size and number of adipocytes and measures of body fat in boys and girls 10 to 18 years of age.

In 111 boys and girls, 10 to 18 yr of age, body density was measured by underwater weighing, and the size of adipocytes in adipose tissue from the buttocks was measured by the osmium tetroxide method. From these two measures, estimates of percentage body fat, total body fat, and adipocyte number were computed for most of the children. Their skeletal age was also calculated by an acceptable method. Across chronological age, the girls have significantly larger mean values of total and percentage body fat and larger and more numerous adipocytes than the boys. The mean number of adipocytes in each sex is within adult levels, as is the mean size of the adipocytes in the girls. The boys' mean adipocyte size is below the adult level. There are negative, significant correlations between percentage body fat and chronological or skeletal age in the boys, and positive significant correlations between total body fat and chronological or skeletal age in the girls. Also, adipocyte size is positively correlated with percentage body fat but only in the boys. With the effects of chronological age removed, percentage body fat was significantly and negatively correlated with skeletal age in boys only. All other correlations among the variables were not statistically significant.

Adipocytes and adiposity in adults.

Measures of adipocyte size and body density were collected from 217 nonobese adults 20 to 50 yr of age, and estimates of total body fat, percentage body fat, and adipocyte number were calculated. Women had a greater percentage body fat than men in every age group except the oldest. Women had significantly greater amounts of total body fat and larger adipocytes than men in the 20- to 24-yr group, but men had significantly greater amounts of total body fat than the women in the 45- to 50-yr group. Adipocyte number, total body fat, and percentage body fat are each positively correlated with age in both sexes. Adipocyte size is not correlated with age but is positively correlated with total and percent body fat in men and women irrespective of age. These cross-sectional data suggest that adipocyte number, rather than being stable during adulthood, increases with age and is associated with corresponding increases in total and percentage body fat.

Effects of hypocaloric diet low in essential fatty acids on in vitro human adipose tissue prostaglandin production and essential fatty acid status.

Very-low-calorie, fat-free defined-formula diets have been routinely used to treat obese patients. However, the effect of feeding a defined-formula diet low or devoid of essential fatty acids (EFAs) on EFA metabolism has not been determined. The aim of this investigation was to determine the effect of 400 kcal/day of Optifast 70 on EFA metabolism as determined by serum and adipose tissue levels of omega-6 fatty acids and measurements of in vitro human adipose tissue prostaglandin production. Five obese subjects entered the study after 1 wk of weight maintenance and then were placed on 12 wk of weight reduction. Blood and tissue samples were obtained before and after 4, 8, and 12 wk of weight reduction. Subjects tolerated 12 wk of dieting without any adverse reactions and lost an average of 21.7 +/- 7.0 kg. There was no significant effect of weight reduction on the levels of linoleic or arachidonic acid found in adipose tissue. There was a significant decrease in adipose tissue prostaglandin production of prostacyclin I2, measured as 6-keto-PGF1 alpha, after 12 wk of weight reduction. There was no significant change in the levels of thromboxane A2, measured as TXB2. There was a significant increase in serum arachidonic acid levels with no change in linoleic acid levels. The results demonstrated that the use of a diet devoid of EFA had no significant effect on omega-6 EFA metabolism as measured by serum and tissue levels and the ability of adipose tissue to produce prostaglandins in vitro.

Effect of emulsions of medium and long chain triglyceride on human adipose tissue prostaglandin production in vitro.

Preliminary in vitro studies have been performed to assess the effect of experimental lipid emulsions of varying fatty acid composition on human adipose tissue metabolism. Subcutaneous human adipose tissue was obtained during elective surgery and placed in tissue culture. Physical mixtures of long chain triglyceride (LCT) and/or medium chain triglyceride (MCT) were added to the tissue culture medium so that the final concentration was 400 mg/dl. After a 3-day incubation period the tissue was harvested, placed in buffer and used to determine in vitro production of the prostaglandins prostacyclin I2 (measured as its stable endproduct 6-keto PGF1 alpha), thromboxane A2 (measured as TXB2), and prostaglandin E2. Measurements of the fatty acid profile found in the neutral- and phospholipid fraction of the adipose tissue and fat cell size were also made. The results demonstrate that samples incubated in 100% MCT had the most significant increase in prostaglandin production whereas those incubated in 100% LCT had the most significant decrease in activity of the three prostaglandins assayed, when compared to controls. The addition of LCT to MCT caused a dose-related decrease in adipose tissue prostaglandin production. There were no significant changes in the profile of fatty acids found in the neutral- or phospholipid fraction of adipose tissue. The results indicate that the relative level of MCT/LCT incubated with human adipose tissue has a significant effect on prostaglandin production.

The effect of medium and long chain triglyceride on human adipose tissue metabolism.

Studies have been performed to assess the effects, in vivo and in vitro, of lipid emulsions on human adipose tissue prostaglandin production. Subcutaneous adipose tissue obtained either during elective surgery or by needle aspiration was studied in tissue culture or by using a perifusion apparatus. Physical mixtures of emulsions of long chain triglyceride (LCT) and/or medium chain triglyceride (MCT) were added to the tissue culture medium so that the final concentration was 400 mg/dl. After a 3-day incubation period the tissue was harvested, placed in buffer and used to determine in vitro production of prostaglandin E2, prostacyclin I2 (measured as its stable end product 6-keto PGF1 alpha) and thromboxane A2 (measured as TXB2) by radioimmunoassay. The results demonstrated that samples incubated in 100% MCT had the most significant increase in prostaglandin production, while those incubated in 100% LCT had the most significant decrease in activity of the three prostaglandins assayed. The addition of LCT to MCT caused a stepwise decrease in adipose tissue prostaglandin production. The data suggest a pharmacological rather than a physiological effect of lipid emulsions containing MCT and/or LCT on adipose tissue prostaglandin production. In vivo effects of a 20% safflower oil emulsion, containing high levels of the essential fatty acid linoleate, were assessed in five pediatric patients. Adipose tissue was obtained before and after two and four weeks of treatment. Fatty acid profiles and prostaglandin production were determined. The results demonstrated that intravenous fat infusion increased the concentrations of linoleic and arachidonic acids found in adipose tissue within a short interval.(ABSTRACT TRUNCATED AT 250 WORDS)

Weight reduction in young obese children. I. Effects on adipose tissue cellularity and metabolism.

A 10-year longitudinal study was conducted on 16 prepubescent youngsters who had undergone successful weight reduction. Their ages ranged from 2 to 10 years when the study began. In all subjects, weight reduction proceeded only by a decrease in adipose cell size (from 0.62 +/- 0.02 to 0.46 +/- 0.02 micrograms lipid per cell) and resulted in a corresponding 33% decrease (from 177 +/- 6 to 144 +/- 5%) in percent ideal body weights. Cell numbers did not change appreciably during the period of weight loss (29.4 +/- 2.6 versus 28.7 +/- 2.3 x 10(9) total adipocytes). Three years after the start of the study, 14 of 20 youngsters had maintained their reduced percent ideal body weights, including eight who remained below 130% ideal body weight. Ten years later, only four remained below 130% ideal body weight. All four children had total adipose cell numbers below 20 x 10(9) total adipocytes at the start of the weight reduction program, a value below the lower limit for adult normal weight subjects. Thirteen other children have maintained or decreased their initial percent ideal weights. The remaining nine youngsters have further increased their percent ideal body weights. In vitro metabolic studies of the patient's adipocytes revealed a greater than 50% depression of epinephrine-stimulated lipolysis pre- and immediately postweight reduction; this decrease persisted for the entire period of study, irrespective of the maintenance of a normal percent ideal body weight. At the same time, normal 150% increases in the in vitro production of 14CO2 from [1-14C]glucose in the presence of insulin occurred.

Regulation of glucose-6-phosphate dehydrogenase activity during caloric restriction in human adipose tissue.

Glucose-6-phosphate dehydrogenase activity was significantly lower in adipose tissue of human subjects after 7 days of severe caloric restriction on low-carbohydrate diets and had returned to normal values 4 days after the subjects resumed normal diets. Three other enzyme activities (malate-NADP dehydrogenase, oxaloacetate decarboxylating; ATP-citrate lyase and 6-phosphofructokinase) were not significantly affected by these dietary changes. These results are consistent with separate control of glucose-6-phosphate dehydrogenase activity versus other 'lipogenic' enzyme activities in human adipose tissue.

Circulating factors affect 6-phosphofructokinase activity in human adipose tissue.

6-Phosphofructokinase activity was lower in adipose tissue of obese, insulin-resistant subjects studied at stable body weight than in nonobese controls. This difference was absent during weight loss due to an increase in 6-phosphofructokinase activity in the obese subjects; the change suggested possible regulation by circulating factors. In an initial test of this hypothesis, blood serum collected from obese subjects at stable weight and incubated with adipose tissue in vitro produced lower 6-phosphofructokinase activity than did sera from nonobese controls.

Observatons on the growth and metabolic functions of cultured cells derived from human adipose tissue.

The growth and metabolic activity of cultured cells derived from human adipose tissue (CAT cells) were studied and compared to cultured skin fibroblasts. The morphological appearance of the CAT cells was distinctly different from that of fibroblasts. The growth rate of CAT cells as measured by 3H-thymidine incorporation was much slower than the fibroblast growth rate. Cultured CAT cells synthesized significantly 14C-glucose, while fibroblast cultures had a higher metabolic rate as measured by CO2 production. Insulin stimulated 3H-thymidine incorporation in both CAT and fibroblast cultures. The CAT cells did not show a consistent insulin response of lipid or CO2 production, but this may be a reflection of donor age or nutritional status. Even though the CAT cell may be a type of stromal cell peculiar to adipose tissue rather than a preadipocyte or adipocyte, it may prove useful in studies of human obesity.