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Biomedical subjects

U Smith

Publications and source records attributed to U Smith.

At least 217 records · Page 12Linked to original sources
PubMed1978

Isolation and characterization of cells from rat adipose tissue developing into adipocytes.

To identify cells developing into adipocytes by accumulation of triglyceride, rat epididymal fat pad cells from small rats were exposed to (3)H-labeled chylomicron fatty acids in vivo and then liberated with collagenase. Tissue remnants were removed by filtration and mature fat cells by flotation. Aggregating cells were then removed by filtration through a 25- micro m nylon screen. Further purification of cells labeled in vivo was obtained by removing floating cells from those adhering to the bottom of a culture dish. The adhering cells multiplied to a confluent monolayer when cultured in Medium 199 containing serum, glucose, insulin, and a triglyceride emulsion. The cells then gradually enlarged due to granulation of the cytoplasm by a lipid-staining material. After about 2 weeks these granules had coalesced forming mature adipocytes of typical signet-ring appearance. Free adipocytes could then be recovered from the cultures by collagenase treatment. After about 2 weeks of culture these cells had the same size (about 30 micro m) as adipocytes recovered in the original collagenase preparation of the rat epididymal fat pad. They contained triglyceride lipase activity and incorporated glucose into triglycerides to the same extent as cells developed in vivo but had higher lipoprotein lipase activity. In vitro, heparin in a low concentration, prostaglandin E(1), isobutylmethylxanthine, and cholera toxin markedly promoted the development of these cells into adipocytes. This could be shown to occur almost completely indicating that this fraction of cells was homogeneous and consisted of cells with the capacity to form adipocytes. The duplication time was about 2 days and did not change with subculturing. Preadipocytes could be obtained by density gradient centrifugation, isolating triglyceride-containing cells either directly from the pad or after 3 days in culture. All of these cells developed into adipocytes as described above but did not multiply as readily. It was concluded that cells from the epididymal fat pad from small rats can be isolated in a homogenous fraction that develops in culture into cells of identical morphology and function as adipocytes formed in vivo. The differentiation of these cells into adipocytes may be manipulated in vitro.

Adipose Tissue↗
PubMed1978

Overweight in women--metabolic aspects. The population study of women in Göteborg 1968--1969.

In a population sample of 1462 women aged 38--60 years, those with overweight were studied separately and compared with the women in the total population sample. Overweight was defined as the upper 5% of a weight index in the various ages studied and the weight index as (formula: see text). Significant differences, with higher values in the overweight women, were found for serum triglycerides, serum uric acid and arterial BP. Smoking was significantly less common in the overweight women. Serum cholesterol was similar in overweight women and in women in the total sample. Higher values for some risk factors for ischaemic heart disease in the overweight group of women thus seemed to be compensated to some extent by a lower number of smokers in this group.

Adult↗
PubMed1977

Physical training in human hyperplastic obesity. IV. Effects on the hormonal status.

Severly obese subjects and sex- and age-matched controls underwnet physical training during a 6-wk period. Evidence of training was shown in all subjects by increased aerobic power. Before training the obese subjects were characterized by the following abberations: decreased glucose tolerance, hyperinsulinemia, elevated blood glycerol and plasma free fatty acids, and a blunted plasma growth hormone response during glucose tolerance. Noradrenaline output was elevated, a finding of potential interest for the explanation of increased lipolysis, blood pressure, and heart size in obesity. With training the following changes were found:In the controls there was evidence for the beginning of a decrease of adipose tissue mass. In the obese, however, body weight, body fat, or fat cell size did not decrease during training. Plasma insulin decreased, and a corresponding increase of plasma glycerol was seen. Glucose tolerance was not changed, and this, together with decreased plasma insulin, indicated an increase insulin sensitivity of the periphery. Changes in noradrenaline or growth hormone during training could not explain this increased sensitivity. Urinary cortisol output was found to decrease after training in the obese; this might be interpreted as a decrease in cortisol secretion allowing a more effective insulin action on the periphery.

Adult↗
PubMed1977

Body fat and adipose tissue cellularity in infants: a longitudinal study.

Body fat, fat cell size, and fat cell number were determined in a longitudinal study on 16 normal-weight infants during the age period 1-18 mo. The methods used included whole-body counting of 40K for determination of body fat and adipose tissue biopsies. A new method of calculation of body fat in infants is presented. No sex differences were found. Body fat expressed as per cent of body weight increased from 16.2% to 28.1%. From 1 to 12 mo of age the expansion of body fat was explained by and increase in fat cell size, while in the age period 12-18 mo it was mainly due to an increase in fat cell number. At 18 mo lthe fat cell size was the same as in 8-yr-old girls and 22-yr-old women (normal-weight females previously studied). The fat cell number at 18 mo, however, was far below the number at 8 yr of age, as well as the still higher number of the 22-yr-old women.

Adipose Tissue↗
PubMed1977

Human adipose tissue in culture. VII. The long-term effect on growth hormone.

Biopsies of human adipose tissue were cultured for one week in vitro with or without different concentrations of human growth hormone (GH). After preincubation they were incubated in vitro for 2 hours analogous to the technique generally used for short-term experiments. The release of glycerol and incorporation of glucose into triglycerides were measured under basal conditions as well as in the presence of insulin or noradrenaline. An impairment in the basal glucose incorporation rate was found after the culture period with GH, but there was no concomitant effect on lipolysis. The effect of insulin on glucose incorporation was stimulating to the same extent as in the controls but the metabolis rate was even in the presence of insulin still below that of the controls. The effects of noradrenaline and of insulin on lipolysis were similar to those in the control group. It is concluded from the present study that a direct "diabetogenic" effect of GH on human adipose tissue can be detected. This effect developed successively over the seven days that the incubations were performed. It was due to a diminished basal rate of glucose incorporation and not to a direct resistance to the action of insulin and it was not related to increased lipolysis.

Adipose Tissue↗
PubMed1977

Effect of age on human adipose tissue metabolism and hormonal responsiveness.

The effects of age and fat cell size on the metabolism of white human adipose tissue were analysed independently. Abdominal subcutaneous adipose tissue specimens were obtained from children varying in age from 0-15 years and from adults (mean age +/- S.D.; 38.2 +/- 14.1 years). The basal rates of lipolysis and glucose incorporation into lipids were considerably higher in children than in adults even when differences in fat cell size had been taken into account. Lipolysis in response to a maximal concentration of noradrenalin was higher in fat cells from children. However, on a percentage basis the responsiveness to this agent was similar in children and adults. Irrespective of age, glucagon did not elicit a lipolytic response. Thus, it does not seem that the increased lipolysis known to occur in vivo in the neonatal period is due to a direct effect of glucagon on white adipose tissue. However, the overall lipolytic capacity is increased in fat cells from children.

Adipose Tissue↗
PubMed1977

Adipose tissue cellularity in relation to prognosis for weight reduction.

Ninety obese adult women were analysed with respect to adipose tissue cellularity and divided into hypertrophic, hyperplastic and combined groups of obesity. Their spontaneous body weight development was analysed over a period of six years. A reference group, with normal body weight, gained weight at an average of 0.25 kg per year. Patients with hyperplastic and combined forms of obesity gained significantly more (2.5 and 3.1 kg per year, respectively) when essentially untreated. The increase for the patients with hypertrophic obesity did not differ significantly from the reference group. During a standardized treatment period on an energy reduced diet (1100 kcal/day or 4600 kJ/day) the hypertrophic, hyperplastic and combined groups reduced by 11, 15 and 20 kg, respectively. There were strong positive correlations between total weight reduction and rate of weight reduction on the one hand and FCN and initial body weight on the other. The combined and hyperplastic groups were on average able to maintain their reduced weight for 12 and 15 weeks, respectively, while the hypertrophic group managed for 51 weeks. There was a strong negative correlation between duration of steady weight after weight reduction and FCN. When the relapse started the rate of regain was three times faster in the hyperplastic and combined groups than in the hypertrophic group. The rate of regain correlated positively with FCN. Thus, the patients demonstrated a characteristic three phase pattern in weight change with a period of reduction followed by periods of steady weight and of weight gain. The higher FCN, the faster this cycle was completed. It is concluded that the long-term prognosis for weight reduction is worse for hypercellular forms of obesity than for the hypertrophic form. However, this does not mean that patients with hypercellular forms of obesity should not be treated at all since their serious spontaneous weight development might be lessened by repeated treatments.

Adipose Tissue↗
PubMed1977

Effects of submaximal physical exercise on adipose tissue metabolism in man.

In order to follow early metabolic adaptations in adipose tissue, which may lead to a decrease in fat cell size and body fat obtained by physical training, two sets of experiments were performed. Obese subjects and a control group exercised on a bicycle at two-thirds of maximal working capacity for one hour. Twenty-four hours thereafter, either on ad libitum diet, or on an isocaloric diet supplemented with calories corresponding to the expanded calories during the work load, an adipose tissue biopsy was taken and fat cell metabolism studied. In obese subjects on and ad libitum or on an isocaloric diet the lipolytic process was increased after the exercise but no significant effects were found on the rates of glucose metabolism. Furthermore, a relationship between cell surface and metabolism was found before, but not after, the work in all groups. No changes were seen in lipoprotein lipase activity. Obese subjects on a controlled diet showed a somewhat higher insulin and catecholamine responsiveness of adipocytes than was the case in the obese subjects on an ad libitum diet. This may well be due to the differences in carbohydrate intake, a factor of importance for hormonal responsiveness of fat cells. The increased basal lipolysis after exercise may be caused by the release of lipolytic hormones, and may well be the first sign of an adaption of the organism to diminish the fat stores as seen in physically trained subjects.

Adipose Tissue↗
PubMed1976

Human adipose tissue in culture. IV. Evidence for the formation of a hormone antagonist by catecholamines.

Explants of human adipose tissue were cultured for several days with noradrenaline (NA). After the culture period the explants were carefully washed, preincubated and then incubated for 2 h by a technique analogous to those generally used to study adipose tissue metabolism. The results show that explants cultured with NA were considerably less responsive to the acute lipolytic effect of catecholamines than explants not previously exposed to NA. The diminished responsiveness could not be reversed by the addition of phentolamine or by preincubating the explants with a prostaglandin antagonist and it was dependent upon the concentration of noradrenaline used in the culture medium as well as upon the period of time that the explants were exposed to the hormone. The cyclic AMP (cAMP) levels did not increase in response to NA in these explants. Addition of theophylline or dibutyryl cAMP elicited a lipolytic response. However, the phosphodiesterase levels were not increased in the explants cultured with noradrenaline. When freshly excised tissue specimens were incubated in the culture medium which had previously contained NA the acute lipolytic effect of catecholamines was blunted. The results indicate that an antagonist is formed during the incubation with NA which inhibits the responsiveness to catecholamines. The effect of the antagonist seems to be exerted at a step prior to the formation of cAMP.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1976

Human adipose tissue in culture V. Studies on the metabolic effects of insulin.

Specimens of human adipose tissue were cultured for one week with or without the addition of insulin. The basal as well as the noradenaline-stimulated lipolysis were enhanced in the explants cultured with insulin, showing that the long-term effect of the hormone is lipolytic. However, an acute antilipolytic effect of insulin could be demonstrated in these explants in the subsequent short-term incubations. The basal rate of glucose incorporation into the lipids was enhanced in the explants cultured with insulin. When insulin was added in the short-term incubations these explants did not further respond to the hormone while this was the case with the explants cultured without insulin. Thus, it seems that prolonged exposure to insulin leads to a diminished acute effect of the hormone on glucose metabolism. However, the same explants responded to the antilipolytic effect showing that insulin was able to bind itself to the membrane. The activities of hexokinase (HK), glucose-6-phosphage dehydrogenase (G6PDH), pyruvate kinase (PK) and lactate dehydrogenase (LDH) were increased in large fat cells both in freshly excised tissue and in cultured explants. However, the activity of phosphofructokinase (PFK) did not correlate with the cell size. The presence of insulin during the culture period enhanced the activities of G7PDH, PK, and LDH, while this was not found for HK or PFK. The data thus suggest that the metabolic capacity of human fat cells is enhanced by long-term exposure to insulin. Although enzyme induction could be shown for G6PDH, PK and LDH it seems unlikely that this is of importance for the increased rates of glucose metabolism in these explants since the rate-limiting enzymes, HK and PGK, were not increased. Most probably, then, this stimulating effect of insulin is exerted on the membrane and the rate of glucose transport.

Adipose Tissue↗
PubMed1976

Influence of cell size on the effects of insulin and noradrenaline on human adipose tissue.

In the present study dose-response relationships of the effects of noradrenaline and insulin on fat cells of different sizes were performed. Adipose cells larger than 100 mum were more responsive (expressed as absolute effects) to the lipolytic action of noradrenaline as well as to the antilipolytic effect of insulin. This suggests that in the larger cells the capacity, i.e. the sum of factors contributing to the ability to stimulate or inhibit the metabolic rates, was greater than in the smaller ones. In contrast the sensitivity to these agents, i.e. the readiness to respond, was not different between small and large cells. It is shown that the concentrations of insulin needed to obtain an antilipolytic effect is far below that needed to stimulate glucose incorporation. This discrepancy in insulin concentrations required may be due to binding of insulin to receptors with different affinity.

Adipose Tissue↗
PubMed1976

Studies of the dual effects of halothane on the lipolysis of human fat cells.

Halothane has dual effects on lipolysis of human adipose tissue: at low tissue concentrations a stimulatory effect is found, while at higher tissue concentrations lipolysis is inhibited. The lipolytic resonse of human adipose tissue was studied in vitro with or without halothane, the phosphodiesterase inhibitor theophylline, the lipase activator dibutyryl cAMP(dbcAMP), the alpha-receptor antagonist phentolamine, the nonselective beta-receptor antagonist propranolol, and the selective beta1-receptor antagonist practolol. In the absence of beta-receptor antagonists low concentrations of halothane stimulated lipolysis, This effect was blunted by beta-receptor antagonists, indicating that halothane at low tissue concentrations may directly stimulate the beta-receptors. The inhibitory effect of higher tissue concentrations of halothane was not the result of increased alpha-receptor activity since addition of phentolamine did not inhibit this effect. High concentrations of theophylline or dbcAMP increased lipolysis in specimens exposed to halothane, but the lipolytic rate was still less than that found in specimens not exposed to halothane. The data thus indicate that the inhibitory effect of halothane is exerted at a step beyond the formation and degradation of cAMP.

Adipose Tissue↗
PubMed1976

Effects of halothane on the metabolism of human adipose tissue.

The metabolism of specimens of human adipose tissue exposed to different concentrations of halothane was studied. Halothane was added to the incubation medium directly or via the gas phase above the medium. The basal lipolysis was significantly increased by low concentrations of halothane. Higher concentrations clearly diminished the lipolysis, but here, in spite of the inhibitory effect on the basal lipolysis, the lipolytic effect of noradrenaline expressed as percent increment was increased. The rate of lipid synthesis from glucose was reduced when halothane was present in the gas phase. The effect of insulin on glucose metabolism was not affected by the presence of halothane, while the antilipolytic action was abolished by high concentrations of halothane. The results show that halothane may exert dual effects on the mobilization of lipids from human adipose tissue; at low concentrations halothane enhances the basal lipolysis, while at higher concentrations it exerts inhibitory effects.

Adipose Tissue↗
PubMed1976

Human adipose tissue in culture. VI. Effect of age on cell size and lipolysis.

Biopsies of subcutaneous adipose tissue were taken from children varying in age from a few hours to 15 years. In 63 children the cell diameter was determined. Weight in relation to height was normal. At an average the fat cell weight was 0.05 mug in the new-born, but adolescent values were reached within the first year of life. Biopsies from 23 children were incubated for one week in vitro. Cell size was not changed significantly during this period. Glycerol release was strongly correlated to cell size and the long-term effect of insulin on the lipolysis was found to be stimulating as previously shown for adults. At the same cell size basal lipolysis was higher in children below one year of age than later in life. It is concluded that the tissue culture method may be used for studies of adopose tissue from children. Furthermore, the data indicate that there is a difference in adipose tissue metabolism and cell size of children below one year as compared to older children and adults.

Adipose Tissue↗