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Studies of human adipose tissue. Adipose cell size and number in nonobese and obese patients.

The cellular character of the adipose tissue of 21 nonobese and 78 obese patients has been examined. Adipose cell size (lipid per cell) was determined in three different subcutaneous and deep fat depots in each patient and the total number of adipose cells in the body estimated by division of total body fat by various combinations of the adipose cell sizes at six different sites. Cell number has also been estimated on the basis of various assumed distribution of total fat between the subcutaneous and deep fat depots. Obese patients, as a group, have larger adipose cells than do nonobese patients; cell size, however, varies considerably among the fat depots of individuals of either group. The variation in cell size exists not only between, but also within subcutaneous and deep sites. Estimates of total adipose cell number for a given individual based upon cell size can, therefore, vary by as much as 85%. On the basis of these studies it is suggested that the total adipose number of an individual is best and most practically estimated, at this time, by division of total body fat by the mean of the adipose cell sizes of at least three subcutaneous sites. IRRESPECTIVE OF THE METHOD BY WHICH TOTAL ADIPOSE CELL NUMBER IS ESTIMATED, TWO PATTERNS OF OBESITY EMERGE WITH RESPECT TO THE CELLULAR CHARACTER OF THE ADIPOSE TISSUE MASS OF THESE PATIENTS: hyperplastic, with increased adipose cell number and normal or increased size, and hypertrophic, with increased cell size alone. These two cellular patterns of obesity are independent of a variety of assumed distributions of fat among the subcutaneous and deep depots. When these different cellular patterns are examined in terms of various aspects of body size, body composition, and the degree, duration, and age of onset of obesity, only the latter uniquely distinguishes the hyperplastic from the hypertrophic: hyperplastic obesity is characterized by an early age of onset, hypertrophic, by a late age of onset. These studies indicate that there are two distinct periods early in life during which hypercellularity of the adipose tissue are most likely to occur: very early within the first few years, and again from age 9 to 13 yr.

Adipose Tissue

Lipogenesis in genetically diabetic (db/db) mice: developmental changes in brown adipose tissue, white adipose tissue and the liver.

Developmental changes in lipogenesis have been examined in interscapular brown adipose tissue (BAT), epididymal white adipose tissue and the liver of genetically diabetic (db/db) mice and their normal siblings. Lipogenesis was measured in vivo with 3H2O, from weaning (21 days of age) until 20 weeks of age. Hyperinsulinaemia was evident in db/db mice at all ages. Low rates of lipogenesis were observed at weaning in tissues of both groups of mice, but the rate rose rapidly in the first few days post-weaning. In normal mice, peak lipogenesis was obtained in each tissue at 4-5 weeks of age, and there were no major changes (on a whole-tissue basis) thereafter. A different developmental pattern was apparent in db/db mice. The rate of lipogenesis in BAT rose sharply after weaning, reaching a peak at 26 days of age (several times higher than normal mice), and then falling rapidly such that by 45 days of age it was lower than in normal mice; at age 20 weeks lipogenesis in BAT of the diabetic animals was negligible. In white adipose tissue of the db/db mutants lipogenesis (per tissue) reached a maximum at 5 weeks of age, and fell substantially between 10 and 20 weeks of age. Hepatic lipogenesis in the db/db mice rose progressively from weaning until 8 weeks of age, and then decreased. Except at weaning, hepatic lipogenesis (per tissue) was much greater in db/db mice than in normal mice, and the liver was a more important site of lipogenesis in diabetic mice than in normals, accounting for up to 60% of the whole-body total. In contrast, BAT accounted for a considerably smaller proportion of whole-body lipogenesis in db/db mice than in normal mice. It is concluded that there are major developmental differences in lipogenesis between tissues of db/db mice, and between diabetic and normal animals. The data suggest that there is an early and preferential development of insulin resistance in BAT of the db/db mutant.

Adipose Tissue

[Behavior of back fat thickness, the activity of NADP-dependent dehydrogenases from adipose tissue and adipose tissue constituents fat and protein and their evidence for energy metabolism in dairy cows].

Studies were conducted into 60 Friesian dairy cattle in the GDR for determination of dorsal fat thickness (DFT), activities of glucose-6-phosphate dehydrogenase (GPDH) and isocitrate dehydrogenase (ICDH) in adipose tissue, concentrations of fat and protein in adipose tissue, 2 weeks ante partum as well as 0, 2, 4, 6, 8, 12, 16, 20, 28, 36 weeks post partum, and liver fat levels, 2 and 4 weeks post partum. DFT, ICDH, GPDH, ICDH-GPDH ratio, fat level, fat-protein quotient, changes in DFT, GPDH, and fat-protein quotient exhibited significant relations with the weeks of lactation. The above 60 experimental cows were subdivided by 6 groups of half-siblings consisting of 10 animals each. Significant differences were found to exist between these groups of half-siblings with regard to DFT, GPDH, ICDH-GPDH ratio, and fat-protein quotient. Within each of the half-sibling groups, significant differences were found to exist between individuals for DFT, ICDH, GPDH, ICDH-GPDH ratio, and fat-protein quotient. The above parameters can be used to describe the energy metabolism of dairy cow via quantitative and temporal curves of fat mobilisation and fat deposition. In the context of both animal health and breeding, more attention should be given to determination of mobilisation and deposition of fat as well as to the post partum energy deficit.

Adipose Tissue

Regulation of cholesterol storage in adipose tissue.

Adipose tissue is a major site of cholesterol storage. In an attempt to define mechanisms controlling this process, a variety of nutritional and metabolic alterations were employed and their effects on adipose tissue cholesterol levels were determined by direct chemical analysis. When rats were raised on Purina chow, a linear increase in the cholesterol/DNA ratio in relation to animal weight (from 120 g [5-6 wk] to 700 g [2 yr]) occurred. The rate of cholesterol accumulation was related to the dietary cholesterol load. Cholesterol accumulation by adipose tissue also occurred in rats raised on a cholesterol-free diet and reached levels exceeding those observed in animals fed on a diet containing 0.05 or 0.1% (w/w) cholesterol. In rats maintained on semisynthetic diets containing 0 to 5% (w/w) cholesterol, the serum cholesterol concentration was inversely related to the dietary concentration, suggesting that feedback inhibition of cholesterol formation may be an important determinant of serum cholesterol levels in this species. Early dietary alterations affected adipose tissue levels later in life. Net cholesterol mobilization from adipose tissue also occurred after acute starvation. Comparison of obese mice with nonobese littermate controls showed that the size of the adipose cholesterol pool was proportional to the degree of adipocity because the amount of cholesterol stored per unit glyceride mass was identical. Adipose tissue cholesterol was not affected by animal sex. Thus, adipose tissue cholesterol levels were dependent on animal age, dietary cholesterol load, early nutritional deprivations, and the size of the adipose organ itself.

Adipose Tissue

Are the n-3 fatty acids from dietary fish oil deposited in the triglyceride stores of adipose tissue?

Adipose tissue is the chief reservoir of the essential fatty acids (n-3 and n-6). To study the incorporation of the dietary n-3 fatty acids eicosapentaenoic acid (EPA) (20:5) and docosahexaenoic acid (DHA) (22:6), and a unique monounsaturated fatty acid, cetoleic acid (22:1n-11), into adipose tissue, rabbits were fed two different processed fish oils: MaxEPA (high in EPA and DHA; Seven Sea Ltd, Hull, UK) and herring oil (high in cetoleic acid). EPA and DHA increased from 0% of total adipose tissue fatty acid, in the adipose tissue of control rabbits to 2.2% and 4.9%, respectively, in MaxEPA-fed rabbits. The DHA-to-EPA ratio in the adipose tissue was higher than that in the diet, indicating alternative metabolic pathways for EPA. In the adipose tissue of herring-oil-fed rabbits, cetoleic acid increased from 0% to 7.9% of total fatty acids. The deposition of EPA and DHA was 1.8% and 2.8%, respectively. Our data indicated that these unique long-chain unsaturated fatty acids from dietary fish oils were readily incorporated into the fat stores from whence they could be mobilized.

Adipose Tissue

The hydrolysis of cholesterol esters in plasma lipoproteins by hormone-sensitive cholesterol esterase from adipose tissue.

Adipose tissue contains a high level of neutral esterase active against emulsions of cholesteryl oleate. The present studies show that this enzyme can also effectively hydrolyze the cholesterol esters in native rat plasma high density lipoproteins (HDL) and low density lipoproteins (LDL). The hydrolysis of lipoprotein cholesterol esters by a pH 5.2 isoelectric precipitate fraction from the freshly prepared 100,000 X g supernatant of chicken adipose tissue was low, but increased more than 50-fold on activation with cyclic AMP-dependent protein kinase. Rat adipose tissue homogenates were also very active against lipoprotein cholesterol esters, hydrolyzing as much as 60% of the total labeled cholesterol ester in HDL or LDL in 1 h. Activity was optimal at pH 7 and very low at pH 4. No protease activity was detected at pH 7 and, since assays were done in 2 mM EDTA, phospholipase A activity was presumably negligible. The results show that hormone-sensitive cholesterol esterase of adipose tissue has ready access to the neutral lipid core of plasma lipoproteins, either because the enzyme penetrates the polar shell or because the cholesterol ester in the core is exposed, at least intermittently, to allow enzyme-substrate complex formation. Whether or not this enzyme activity plays a role in lipoprotein degradation by adipose tissue remains to be determined.

Adipose Tissue

[Metabolism of sex hormones and adipose tissue].

Adipose tissue is a catchment area for storing, converting and releasing the sex hormones. The role of adipose tissue in the general metabolism of endogenous and exogenous steroids deserves to be considered seeing how big the volume of fat is in the human body. The fatty pool of sex steroids seems to be greater than the plasma pool. Hormones which have been stored can be released by adipocytes into the general circulation even if they have been converted while in the adipocytes. Similarly, androgens are changed by adipose tissue into oestrogens by aromatisation and are liberated. This extraglandular production of oestrogens can have clinical and pathological consequences.

Adipose Tissue

Interaction between insulin and thyroid hormones on the control of carbohydrate and lipid metabolism in rat adipose tissue.

Adipose tissue segments excised from normal rats and from rats rendered experimentally hypothyroid and hyperthyroid retained insulin responsiveness when studied in vitro. Basal rates of glucose oxidation to CO2, conversion into glyceride-glycerol, fatty acids, and total lipids, and the activities of pyruvate dehydrogenase and fatty acid synthetase were enhanced in fat pads from hyperthyroid rats when compared with values seen with tissue from euthyroid animals. The response of each of these parameters was further enhanced by treating tissue from hyperthyroid rats in vitro with insulin. Basal rates of glucose oxidation and the activities of pyruvate dehydrogenase and fatty acid synthetase were depressed as a result of hypothyroidism. However, all of these values could be restored to levels approaching the values seen in the basal state for euthyroid rats when tissue segments from hypothyroid rats were incubated in vitro with insulin. The basal rates for glucose conversion into glyceride-glycerol, fatty acids, and total lipids were not changed by hypothyroidism but retained insulin responsiveness. These data suggest that the insulin-effector system in adipose tissue is not altered by thyroid status and that thyroid hormones may act independently with insulin to regulate glucose and lipid metabolism in this tissue at multiple intracellular metabolic sites.

Adipose Tissue

Fish oil-induced yellow fat disease in rats. II. Enzyme histochemistry of adipose tissue.

Adipose tissue in various stages of fish oil-induced yellow fat disease in the rat had the same acid phosphatase and 5-nucleotidase activity pattern as similar stages of the disorder in mink and pig. A weak acid phosphatase and 5-nucleotidase activity was seen in interstitial lipofuscin-laden macrophages in "stage M" yellow fat disease without fat cell degeneration. Activity of these macrophagic enzymes increased when there was fat cell degeneration ("stage S" and "stage E" yellow fat disease). This different phosphatase activity in the same cell type may result from phagocytosis of substrates with variable digestibility. Macrophages directly surrounding affected fat cells in steatitis areas ("stage S" and "stage E") had strong acid phosphatase and 5-nucleotidase activity. As in the pig, increased 5-nucleotidase activity was found in affected fat cells, which probably indicates plasma membrane damage. Increased nonspecific esterase activity occurred around affected fat cells. Only a small part of this esterase activity originated from inflammatory cells. This indicates that an increase of esterase activity in degenerating adipose tissue may be an endogeneous process in this tissue.

Acid Phosphatase

Angiogenic activity of adipose tissue.

Adipose tissue has been used to promote wound healing and to revascularize ischemic myocardium. We explored whether fat from various sources was angiogenic in the cornea. Rabbit subcutaneous and omental fat induced grossly visible neovascularization of all rabbit corneas studied, and at a similar rate and intensity. Neovascularization was not observed in any cornea following control implantation of liver or muscle. Neovascularization was blocked in all rabbits in which indomethacin was administered orally 3 days before implantation of fat and continued following implantation, suggesting that prostaglandins are associated with fat induced angiogenesis.

Adipose Tissue

Changes in the lipogenic response to feeding of liver, white adipose tissue and brown adipose tissue during the development of obesity in the gold-thioglucose-injected mouse.

Lipogenic response to feeding was measured in vivo in liver, epididymal white adipose tissue (WAT) and interscapular brown adipose tissue (BAT), during the development of obesity in gold-thioglucose (GTG)-injected mice. The fatty acid synthesis after a meal was higher in all tissues of GTG-treated mice on a total-tissue basis, but the magnitude of this increase varied, depending on the tissue and the time after the initiation of obesity. Lipogenesis in BAT from GTG mice was double that of control mice for the first 2 weeks, but subsequently decreased to near control values. In WAT, lipogenesis after feeding was highest 2-4 weeks after GTG injection, and in liver, lipid synthesis in fed obese mice was greatest at 7-12 weeks after the induction of obesity. The post-prandial insulin concentration was increased after 2 weeks of obesity, and serum glucose concentration was higher in fed obese mice after 4 weeks. These results indicate that increased lipogenesis in GTG-injected mice may be due to an increase in insulin concentration after feeding and that insulin resistance (assessed by lipogenic response to insulin release) is apparent in BAT before WAT and liver.

Adipose Tissue

Ontogenetical changes in adipose tissue of the cat: convertible adipose tissue.

The ultrastructural characteristics of the inguinal, interscapular, and perirenal adipose tissue in kittens and cats were studied. There were no qualitative differences among adipocytes in the three anatomical areas. The only recorded difference was in the amount of lipids stored in the adipocytes in younger stages. Immediately after birth lipids occupied 25% of the volume in the inguinal area, 15% in interscapular fat tissue, and 10% in perirenal fat tissue. At this stage the adipose tissue morphologically resembled brown adipose tissue (BAT) of rodents. Two weeks after birth, lipids accumulated and adipocytes in the inguinal area became unilocular and appeared similar to white adipose tissue (WAT). A similar transition occurred approx 25 days after birth in interscapular fat and approx 6 weeks after birth in the perirenal area. No morphological signs of any cell degradation or destruction, nor any increased activity of preadipocytes, were seen during this conversion from BAT-like to WAT-like adipose tissue. The conversion of the adipose tissue was correlated with a decrease in vascularization and innervation, a loss of intercellular connections, and a changed mitochondrial population. Mitochondria in multilocular adipocytes resembled those in typical BAT which contain uncoupling protein ("UC-mitochondria"). After conversion to unilocular adipocytes the amount of mitochondria was halved, their cristae even more reduced, and their appearance was of a WAT-type (UCP-lacking mitochondria, which are coupled under physiological conditions; "C-mitochondria"). Since this category of adipose tissue differs from both typical brown and white adipose tissue, the name "convertible adipose tissue" (CAT) is proposed. Apparently adipose tissue from comparatively large mammals is of this convertible type.

Adipose Tissue

Modulation of fatty acid synthesis in vivo in brown adipose tissue, liver and white adipose tissue of cold-acclimated rats.

The present experiment was an appraisal of the relative importance of fatty acid synthesis in brown adipose tissue (BAT) in young 28 or 5 degrees C adapted rats (9 weeks old). With a low-fat diet in vivo incorporation of 3H2O into BAT fatty acids was 8 times lower during the day than during the night and was not modified by a 6-hour fast during the day (28 degrees C). Cold acclimation doubled (night) or increased 8 times (day) BAT lipogenesis. Fasting led to a halving of the diurnal rate. A high-fat diet led to large decrease in synthesis rate during the night but had a weak effect on diurnal synthesis. The specific activity of fatty acids was 3 times lower in phospholipids than in neutral lipids. A comparison between 9- and 15-week-old rats indicated that in older warm-adapted rats BAT lipogenesis decreased by half but that cold stimulation was unaltered. These results were compared with hepatic and epididymal white adipose tissue lipogenesis. In conclusion, we showed that BAT of 5 degrees C rats is an important but not the major site for the conversion of carbohydrate to fat and that the proportional involvement of each tissue is age-dependent.

Acclimatization

Serum triglycerides and fatty acid incorporation into human adipose tissue (TIAT). Their relations with adipose tissue characteristics and glucose tolerance.

Fatty acid incorporation into adipose tissue (FIAT), the metabolic process assimilating plasma triglyceride fatty acids liberated by lipoprotein lipase, was recently found to be lower in hyper- than in normotriglyceridaemia. In the present report, the relation of FIAT to glucose tolerance and adipose tissue morphology and fatty acid composition has been studied in a popoulation of men with normo- and hypertriglyceridaemia, using needle biopsy specimens. In addition, the associations between plasma triglyceride concentration and these factors as well as FIAT were examined by statistical methods. FIAT and GLIAT (glucose incorporation into adipose tissue) activities per cell were positively correlated with fat cell diameter but not with fat cell number. FIAT activities per cell and per unit surface area were lower in hyper- than in normo-triglyceridaemic subjects. The k-value of the i.v.glucose tolerance test and glycerol release from adipose tissue did not correlate with FIAT or GLIAT activities. The proportion of stearic acid in adipose tissue was negatively correlated with the serum triglyceride level and with fat cell diameter, but positively correlated with FIAT. Linolenic acid in adipose tissue correlated positively with the k-value. The negative correlation between serum triglycerides and FIAT remained when the other variables which were significantly correlated with FIAT or the serum triglycerides were entered in partial correlat-on analysis. These results suggest that although low FIAT activity is related in part to other characteristics, it occurs in hypertriglyceridaemia independent of glucose tolerance or various characteristics in fat. With serum triglyceride concentration as dependent variable, stepwise regression analysis was performed, entering all other variables as independent ones. The highest multiple --value was 0.76 (p less than 0.001) and it was obtained with three adipose tissue parameters: FIAT (or GLIAT), content of linolenic acid and of stearic acid. The other parameters did not give rise to any further improvement in the prediction of the serum triglyceride concentration which is better than 50% (R2 = 0.57).

Adipose Tissue

Effects of vitamin B6 deficiency on liver, kidney, and adipose tissue enzymes associated with carbohydrate and lipid metabolism, and on glucose uptake by rat epididymal adipose tissue.

Adipose tissue and liver from vitamin B6-deficient rats have an increased lipogenic capacity. Whether this phenomenon is accompanied by changes in the activities of certain enzymes involved in the metabolism of carbohydrate and lipid, or by altered transport of glucose into adipocytes, has been studied. Five glycolytic enzymes (hexokinase, phosphoglucose isomerase, phosphofructokinase, aldolase, and pyruvate kinase), two pentose phosphate pathway enzymes (glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase), malic enzyme, and ATP citrate lyase were measured in the epididymal adipose tissue, livers and kidneys of vitamin B6-deficient and control rats. Vitamin B6 deficiency did not significantly affect the glycolytic enzyme levels in the tissues studied, or the dehydrogenases measured in adipose tissue and kidneys. Liver glucose-6-phosphate dehydrogenase, and adipose tissue and liver malic enzyme were significantly lowered in deficient rats compared to ad libitum and pair-fed controls. Adipose tissue and liver ATP citrate lyase activities were also significantly decreased by vitamin B6 deficiency. In the presence of insulin, the uptake of glucose and 3-O-methyl glucose, a non-metabolizable sugar, by fat pads from deficient rats was greater than uptake by fat pads from control rats. These observations suggest that the increased glucose utilization by adipose tissue and liver of vitamin B6-deficient rats is not directly related to changes in the enzymes studied, but in the case of adipose tissue, may be explained, at least in part, by enhanced glucose uptake.

ATP Citrate (pro-S)-Lyase

[Obesity and adipose tissue. 2. Hormonal regulation of adipose tissue metabolism].

The effects of hormones on human adipose tissue are reviewed with respect to the pathogenesis, prevention and therapy of obesity. Insulin. The insulin-resistance in the obese is associated with a decrease of the number of insulin receptor sites, which is likely to be secondary to increased insulin levels. Catecholamines. Human adipose tissue contains alpha- and beta-adrenergic receptors. Alterations in the relation of alpha- and beta-adrenergic responsiveness may be important in the pathogenesis of regional forms of obesity. Gastrointestinal hormones. As opposed to adipose tissue of other species lipolytic effects of gastrointestinal hormones were as yet not clearly demonstrated in human fat cells. Prostaglandins were implicated in the pathogenesis of metabolic obesity. However, the effects of these C-20 fatty acids on human adipose tissue remain to be elucidated. Parathyroid hormone has been shown to possess lipolytic activity in vitro. This property may be important under physiological conditions too. Triglyceride storage diseases and lipomatoses are discussed as models for studying impaired hormonal responsiveness in human adipose tissue.

Adipose Tissue

Styrene in adipose tissue of nonoccupationally exposed persons.

Given a styrene tissue/blood partition coefficient of ca. 39 and a relatively low perfusion rate of ca. 0.03 ml/min-g tissue, adipose tissue provides a useful physiologically damped integrative measure of environmental exposure. Styrene in the adipose tissue of nonoccupationally exposed individuals was measured for the first time. Tissue samples obtained from elective surgery patients and postmortem donors were analyzed by capillary gas chromatography and found to contain 1.12 +/- 1.06 (mean +/- SD) ppm styrene. Using these measured tissue levels and an apparent clearance of styrene (defined as the ratio of blood clearance to adipose tissue/blood partition coefficient), environmental intake of styrene was estimated to be 2.23 mg/hr, corresponding to an inhaled concentration of 1.96 mg/m3 (476 ppb). This value is two to three orders of magnitude higher than typical breathing zone air measurements, indicating additional undiscovered sources of styrene exposure.

Adipose Tissue