Regional variation in adipose tissue insulin action and GLUT4 glucose transporter expression in severely obese premenopausal women

Insulin action and GLUT4 expression were examined in adipose tissue of severely obese premenopausal women undergoing gastrointestinal surgery. Fat samples were taken from three different anatomical regions: the subcutaneous abdominal site, the round ligament (deep abdominal properitoneal fat), and the greater omentum (deep abdominal intraperitoneal fat). The stimulatory effect of insulin on glucose transport and the ability of the hormone to inhibit lipolysis were determined in adipocytes isolated from these three adipose depots. Insulin stimulated glucose transport 2-3 times over basal rates in all adipocytes. However, round ligament adipose cells showed a significantly greater responsiveness to insulin when compared to subcutaneous and omental adipocytes. Round ligament fat cells also displayed the greatest sensitivity and maximal antilipolytic response to insulin. We also investigated whether regional differences in fat cell insulin-stimulated glucose transport were linked to a differential expression of the GLUT4 glucose transporter. GLUT4 protein content in total membranes was 5 and 2.2 times greater in round ligament adipose tissue than in subcutaneous and omental fat depots, respectively. Moreover, GLUT4 mRNA levels were 2.1 and 3 times higher in round ligament than in subcutaneous or omental adipose tissues, respectively. Adipose tissue GLUT4 protein content was strongly and negatively associated (r = -0.79 to -0.89, p < 0.01) with the waist-to-hip ratio but not with total adiposity. In conclusion, these results demonstrate the existence of site differences in adipose tissue insulin action in morbidly obese women. The greater insulin effect on glucose transport in round ligament adipocytes was associated with a higher expression of GLUT4 when compared to subcutaneous abdominal and omental fat cells. Moreover, despite the regional variation in GLUT4 expression, an increased proportion of abdominal fat was found to be associated with lower levels of GLUT4 in all adipose regions investigated.     

HIV infection and AIDS among drug injectors at Rio de Janeiro: perspectives and unanswered questions

Determination of the presence and characterization of oestrogen receptors (ERs) in subcutaneous and internal fat depots were performed and compared with ERs in the uterus using ligand binding and immunological techniques. Successful and consistent measurement of ERs in ovine adipose tissue could only be accomplished in animals depleted of endogenous sex steroids by combined ovariectomy and adrenalectomy. Scatchard, sucrose gradient and Western blot analyses all confirmed the presence of ERs in the cytosolic fractions of various adipose and uterine tissues from ovariectomized-adrenalectomized ewes. The approximate Kd values of 0.1-0.4 nmol/l for oestradiol binding in cytosolic fractions of gluteal, omental and perirenal adipose tissues were similar to the expected high affinity binding of Kd 0.35 nmol/l observed in uterine tissue. The binding was specific for oestrogens, as unlabelled diethylstilboestrol and oestradiol effectively competed with labelled hormone for receptor sites and progesterone, R5020, testosterone and dexamethasone all failed to compete. Mean (+/- S.E.M.) concentrations of ERs, expressed as fmol specific binding sites per mg protein, were much lower (P < 0.05) in adipose tissues than in uterine tissue (975 +/- 33). However, the content of ERs was greater (P < 0.05) in subcutaneous gluteal fat (11.5 +/- 0.8) than in the internal omental or perirenal fat (5 +/- 0.6) depots. ERs from adipose and uterine tissues both migrated as moieties of 8S on 5-20% sucrose gradients. Western blot analysis of ERs from uterine and adipose tissues in the presence of protease inhibitors demonstrated an immunostaining band with a molecular mass of 67 kDa.(ABSTRACT TRUNCATED AT 250 WORDS)     

Long-term effects of feeding high carbohydrate diet in pre-weaning period by gastrostomy: a new rat model for obesity

In the present study, we report the long-term metabolic consequences of feeding a milk substitute formula that is high in carbohydrate-derived calories during the suckling period. Male Sprague-Dawley rat pups were raised by gastrostomy on a high carbohydrate (HC) formula or a high fat (HF) formula (which mimicked rat milk composition in macronutrients) during the pre-weaning period (day 4 to 24). These rats were then weaned to a laboratory stock diet and subsequently challenged with a high sucrose diet to augment the development of obesity. The pups receiving the HC formula developed obesity in later life, even though there was no change in the body weight of this group compared to mother-fed (MF) controls or HF formula fed animals during the pre-weaning period. The HC rats were hyperinsulinemic and their growth rates were greater than MF rats starting at day 55. The lipogenic capacity of liver as well as adipose tissues (epididymal and omental) was higher in HC animals compared to MF control animals, as reflected by increases in two key lipogenic enzymes (fatty acid synthase and glucose-6-phosphate dehydrogenase) and in vitro synthesis of lipids. An analysis of adipose tissue morphology in adult rats showed an increase in cell size in epididymal adipose tissue of HC rats compared to the MF group. However, there was no significant difference in cell size in omental adipose tissue between the MF and HC rats. The HF group behaved similarly to the MF control group in growth pattern and measured metabolic parameters.     

Type of milk consumed can influence plasma concentrations of fatty acids and minerals and body composition in infant and weanling pigs

Two experiments using 42 crossbred neonatal pigs to compare the effects of caprine and bovine milk on growth, apparent nutrient digestibility and body composition were conducted. At age 72 h, pigs were removed from their dams and randomly divided into two groups, housed separately in stainless steel metabolism cages and were fed a predetermined amount (300 mL/kg body weight) of pasteurized, nonfortified whole, caprine or bovine milk. Body composition was determined using dual energy X-ray absorptiometry (DXA). In Experiment 1, 22 intact male pigs were used for a 31-d experimental period. There was no significant (P > 0.05) dietary effect on growth, apparent nutrient digestibility or body composition. Significant differences (P < 0.05), however, were observed in plasma of C 8:0, C 10:0 and C 12:0 concentrations. In Experiment 2, 20 pigs (10 intact males and 10 females) were used in a 2 x 2 factorial experiment for 52 d. Pigs fed caprine milk had higher (P < 0.05) plasma concentrations of C10:0 and C12:0 as well as Na, Mg and Zn than those fed bovine milk. At Day 52, pigs fed caprine milk had less body fat (P < 0.001) and higher (P < 0.06) bone mineral density than those fed bovine milk. Drymatter, N and total mineral intake of male pigs was higher (P < 0.05) than female pigs. Also, male pigs had higher (P < 0.05) plasma concentrations of C12:0 than females. This study demonstrates that the type of milk consumed can influence plasma concentrations of fatty acids, minerals and body composition in pigs.     

Lipoprotein lipase activity and its relationship to high milk fat transfer during lactation in grey seals

Lipoprotein lipase regulates the hydrolysis of circulating triglyceride and the uptake of fatty acids by most tissues, including the mammary gland and adipose tissue. Thus, lipoprotein lipase is critical for the uptake and secretion of the long-chain fatty acids in milk and for the assimilation of a high-fat milk diet by suckling young. In the lactating female, lipoprotein lipase appears to be regulated such that levels in adipose tissue are almost completely depressed while those in the mammary gland are high. Thus, circulating fatty acids are directed to the mammary gland for milk fat production. Phocid seals serve as excellent models in the study of lipoprotein lipase and fat transfer during lactation because mothers may fast completely while secreting large quantities of high fat milks and pups deposit large amounts of fat as blubber. We measured pup body composition and milk fat intake by isotope (deuterium oxide) dilution and plasma post-heparin lipoprotein lipase activity in six grey seal (Halichoerus grypus) mother-pup pairs at birth and again late in the 16-day lactation period. Maternal post-heparin lipoprotein lipase activity increased by an average of four-fold by late lactation (P = 0.027), which paralleled an increase in milk fat concentration (from 38 to 56%; P = 0.043). Increasing lipoprotein lipase activity was correlated with increasing milk fat output (1.3-2.1 kg fat per day) over lactation (P = 0.019). Maternal plasma triglyceride (during fasting) was inversely correlated to lipoprotein lipase activity (P = 0.027) and may be associated with the direct incorporation of long-chain fatty acids from blubber into milk. In pups, post-heparin lipoprotein lipase activity was already high at birth and increased as total body fat content (P = 0.028) and the ratio of body fat: protein increased (P = 0.036) during lactation. Although pup plasma triglyceride increased with increasing daily milk fat intake (P = 0.023), pups effectively cleared lipid from the circulation and deposited 70% of milk fat consumed throughout lactation. Lipoprotein lipase may play an important role in the mechanisms involved with the extraordinary rates of fat transfer in phocid seals.     

Thrombolytic and antiplatelet action of xanthinol nicotinate (Sadamin): possible mechanisms

Primiparous Holstein cows received recombinant bovine growth hormone (bGH), bovine growth hormone-releasing factor (bGRF), or no treatment from 118 to 181 +/- 1 d. Milk yield was significantly increased with no change in milk fat percentage or composition. The mRNA and protein abundance of the key lipogenic enzymes acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS) were measured in the mammary gland and adipose tissue. We hypothesized that bGH and bGRF treatment would increase the mRNA and protein abundance of ACC and FAS in the mammary gland, with an associated decrease in adipose tissue. Analysis of ACC mRNA and protein abundance in the mammary gland revealed that there was no significant influence of either bGH or bGRF treatment. Analysis of FAS mRNA in mammary gland revealed that both bGH and bGRF significantly increased the abundance. However, quantitation of FAS protein in the mammary gland revealed that neither treatment resulted in increased abundance. In adipose tissue, the mRNA and protein abundance of both ACC and FAS were significantly reduced. The increased substrate required for increased milk fatty acid yield may be provided through redirection of nutrients to the mammary gland away from adipose tissue and through overall increased metabolism of the mammary gland.     

Interstitial fluid concentrations of glycerol, glucose, and amino acids in human quadricep muscle and adipose tissue. Evidence for significant lipolysis in skeletal muscle

To determine the relationship between circulating metabolic fuels and their local concentrations in peripheral tissues we measured glycerol, glucose, and amino acids by microdialysis in muscle and adipose interstitium of 10 fasted, nonobese human subjects during (a) baseline, (b) euglycemic hyperinsulinemia (3 mU/kg per min for 3 h) and, (c) local norepinephrine reuptake blockade (NOR). At baseline, interstitial glycerol was strikingly higher (P < 0.0001) in muscle (3710 microM) and adipose tissue (2760 microM) compared with plasma (87 microM), whereas interstitial glucose (muscle 3.3, fat 3.6 mM) was lower (P < 0.01) than plasma levels (4.8 mM). Taurine, glutamine, and alanine levels were higher in muscle than in adipose or plasma (P < 0.05). Euglycemic hyperinsulinemia did not affect interstitial glucose, but induced a fall in plasma glycerol and amino acids paralleled by similar changes in the interstitium of both tissues. Local NOR provoked a fivefold increase in glycerol (P < 0.001) and twofold increase in norepinephrine (P < 0.01) in both muscle and adipose tissues. To conclude, interstitial substrate levels in human skeletal muscle and adipose tissue differ substantially from those in the circulation and this disparity is most pronounced for glycerol which is raised in muscle as well as adipose tissue. In muscle, insulin suppressed and NOR increased interstitial glycerol concentrations. Our data suggest unexpectedly high rates of intramuscular lipolysis in humans that may play an important role in fuel metabolism.     

Magnetic resonance properties of ex vivo breast tissue at 1.5 T

The magnetic resonance absorption spectrum, T1 and T2 relaxation time distributions, and magnetization transfer properties of ex vivo breast tissue have been characterized at 1.5 T and 37 degrees C. The fraction of fibroglandular tissue within individual tissue samples (n = 31) was inferred from the tissue volumetric water content obtained by integration of resolvable broad-line fat and water resonances. The spectroscopically estimated water content was strongly correlated with that extracted enzymatically (Pearson correlation coefficient 0.98, P < < 0.01), which enabled the assignment of principal relaxation components for fibroglandular tissue (T2=0.04+/-0.01, T1=1.33+/-0.24 s), and for adipose tissue (T2=0.13+/-0.01, T1=0.23+/-0.01 s, and T2=0.38+/-0.03, T1=0.62+/-0.16 s). Th e relaxation components for fibroglandular tissue exhibited strong magnetization transfer, whereas those for adipose tissue showed little magnetization transfer effect. These results ultimately have applicability to the optimization of clinical magnetic resonance imaging and research investigations of the breast.     

Correlated response, competition, and female canine size in primates

The objective of this study was to determine the effect of two probiotics, Saccharomyces cerevisiae (SC) and Aspergillus oryzae (AO), without their culture medium, on the digestion of plant cell wall components in sheep that had been successively defaunated and refaunated. Six sheep fitted with large rumen cannulae were used to study 1) defaunated sheep with no probiotic, 2) defaunated sheep with SC or AO, 3) refaunated sheep with no probiotic, 4) refaunated sheep with SC or AO. The apparent digestibility of the plant cell walls was not altered (P > 0.05) by the probiotics in defaunated sheep but was increased (P < 0.05) with SC (+16%) in refaunated sheep. Simultaneously, SC stimulated the growth of the protozoal population in the rumen. As noted in most previous experiments, the positive effect of the presence of protozoa on plant cell wall digestion (P < 0.001) was confirmed here. The effect (P > 0.05) of SC or AO on in situ ADF digestion was either not significant or negative in defaunated rumens, whereas it became positive in refaunated rumen after a residence time of 12 h. The improvement of in situ ADF digestion due to the presence of protozoa was significant (P < 0.05 for NDF; P < 0.001 for ADF). However, we could not determine whether this was a direct effect of protozoa or an indirect effect operating via bacteria. The limits of the nylon bag technique for evaluating the microbial activity are discussed in relation to the ability of protozoa to enter and grow in the bags, and the pH regulation inside the bags. The pH values below 5.5 noted inside the bags can significantly alter the bacterial and protozoal populations and limit the validity of the technique. SC increased (P < 0.05) the specific activity of CMCase and xylanase of the solid-adherent bacteria (SAB) isolated from the rumen digesta of refaunated sheep. Stimulation of both the bacterial activity and protozoa numbers could explain the positive effect of SC on cell wall digestion in the rumen since the modelling of marker excretion in faeces showed that the ruminal mean retention time of hay measured from the model of Danhoa et al. was not modified (P > 0.05) by either refaunation or the presence of probiotics. AO increased (P < 0.05) the total retention time of the solid particles in the whole digestive tract and increased the ruminal liquid volume in the refaunated animals but it had no effect on the protozoa population or on the polysaccharidase activity of the SAB, which could explain the absence of effect of AO on the total digestibility of plant cell walls. Both probiotics decreased the liquid turnover in defaunated rumens (P < 0.05) but neither had any effect (P > 0.05) on this parameter after refaunation. The improvement of plant cell wall degradation in the whole digestive tract is probably due to a stimulation of digestion at the rumen level as indicated by the higher activity of the SAB in rumen digesta and the growth of protozoa.     

Human preadipocytes display a depot-specific susceptibility to apoptosis

Adipose tissue mass is determined by both the number and volume of adipose cells. Adipose cell number reflects the balance of cell acquisition and cell loss, whereas adipose cell volume represents the balance of lipolysis and lipogenesis. It is well recognized that insulin resistance, NIDDM, and other metabolic disorders are associated more strongly with increased omental adiposity than with subcutaneous adiposity. Depot-related differences exist in adipocyte responses to lipolytic and lipogenic stimuli, in adipocyte apoptosis, and in the potential for preadipocyte replication and differentiation. In the present study, we address the question of whether there might also be a site-specific difference in the susceptibility of human preadipocytes to apoptosis. Paired samples of human omental and subcutaneous preadipocytes from 12 individuals were cultured, and apoptosis was induced by serum deprivation or treatment with tumor necrosis factor (TNF)-alpha for 4 h. Cells were then stained with acridine orange, and apoptotic indices were calculated as the fraction of cells showing nuclear condensation. Under both conditions, in 9 of 11 subjects, apoptotic indices were substantially greater in preadipocytes from the omental depot than in those from the subcutaneous depot, and mean apoptotic indices were more than twofold higher in omental cells (serum-free medium: P < 0.05; TNF-alpha: P < 0.02; paired t test). Omental preadipocytes are therefore more susceptible to two different apoptotic stimuli than subcutaneous preadipocytes, demonstrating another intrinsic site-specific difference between human adipose cells of the two depots. These results suggest that the regulation of adipose tissue distribution in humans could involve depot-specific differences in rates of preadipocyte apoptosis.     

Effects of physiological hypercortisolemia on the regulation of lipolysis in subcutaneous adipose tissue

Cortisol is known to increase whole body lipolysis, yet chronic hypercortisolemia results in increased fat mass. The main aim of the study was to explain these two apparently opposed observations by examining the acute effects of hypercortisolemia on lipolysis in subcutaneous adipose tissue and in the whole body. Six healthy subjects were studied on two occasions. On one occasion hydrocortisone sodium succinate was infused i.v. to induce hypercortisolemia (mean plasma cortisol concentrations, 1500 +/- 100 vs. 335 +/- 25 nmol/L; P < 0.001); on the other occasion (control study) no intervention was made. Lipolysis in the s.c. adipose tissue of the anterior abdominal wall was studied by measurement of arterio-venous differences, and lipolysis in the whole body was studied by constant infusion of [1,2,3-2H5]glycerol for measurement of the systemic glycerol appearance rate. Hypercortisolemia led to significantly increased arterialized plasma nonesterified fatty acid (NEFA; P < 0.01) and blood glycerol concentrations (P < 0.05), with an increase in systemic glycerol appearance (P < 0.05). However, in s.c. abdominal adipose tissue, hypercortisolemia decreased veno-arterialized differences for NEFA (P < 0.05) and reduced NEFA efflux (P < 0.05). This reduction was attributable to decreased intracellular lipolysis (P < 0.05), reflecting decreased hormone-sensitive lipase action in this adipose depot. Hypercortisolemia caused a reduction in arterialized plasma TAG concentrations (P < 0.05), but without a significant change in the local extraction of TAG (presumed to reflect the action of adipose tissue lipoprotein lipase). There was no significant difference in plasma insulin concentrations between the control and hypercortisolemia study. Site-specific regulation of the enzymes of intracellular lipolysis (hormone-sensitive lipase) and intravascular lipolysis (lipoprotein lipase) may explain the ability of acute cortisol treatment to increase systemic glycerol and NEFA appearance rates while chronically promoting net central fat deposition.     

Rheology and filling characteristics of particulate dispersions in polymer melt formulations for liquid fill hard gelatin capsules

OBJECTIVE: In the postmenopausal years, women develop a central pattern of fat distribution and an increased risk of developing cardiovascular disease (CVD). The possibility that these events are related has not been extensively investigated. The object of the present study was to test the hypotheses that, 1) menopause-related differences in lipids are associated with greater estimated intra-abdominal adiposity, and 2) the relationship between individual adipose depots and plasma lipids differs with menopausal status. DESIGN: Cross-sectional. SUBJECTS: 141 healthy pre- and postmenopausal women aged 35-65 y. MEASUREMENTS: Total body fat by hydrodensitometry was used as an index of whole-body adiposity, the sum of five central skinfold measurements as an index of subcutaneous upper-body adiposity, and estimated intra-abdominal adipose tissue (IAF) as an index of visceral adiposity. Fasting plasma concentrations of total cholesterol (total-C), high- and low-density-lipoprotein cholesterol (HDL-C, LDL-C), and triglycerides were used as indices of CVD risk. RESULTS: Postmenopausal women had greater total body fat (P < 0.001), summed central skinfolds (P < 0.01), estimated IAF (P < 0.001), higher plasma concentrations of total-C (P < 0.001), LDL-C (P < 0.001) and triglycerides (P < 0.001), than premenopausal women. The relationship between central skinfolds and LDL-C differed with menopausal status, being significant in pre- but not postmenopausal women. Adjustment for estimated IAF with analysis of covariance decreased menopause-related differences in levels of total-C, LDL-C and triglycerides by approx 40-70%. CONCLUSION: These observations suggest that, 1) menopause-related changes in IAF may adversely affect the plasma lipid profile, and 2) menopausal status affects the relationship between central subcutaneous fat and LDL-C. Studies with measured IAF are needed to confirm present results.     

Gender differences in both spontaneous and stimulated leptin secretion by human omental adipose tissue in vitro: dexamethasone and estradiol stimulate leptin release in women, but not in men

Leptin is a hormone secreted by the adipocytes to serve as a signal to the central nervous system to regulate energy homeostasis. Circulating leptin mainly reflects both total fat mass and the size of constituent adipocytes, although other ancillary hormonal factors may contribute to its blood concentration. Relevant gender differences in leptin concentrations have been reported, but it is not clear whether the elevated leptin levels in women are an intrinsic property of their adipocytes or merely reflect a greater amount of fat reserves. To clarify these points, a systematic study with organ culture from human omental adipose tissue either stimulated or not with steroid hormones was undertaken in samples obtained at surgery from 67 nonobese donors (33 women and 34 men). The assay was standardized in periods of 24 h ending at 96 h, with no apparent tissue damage. Each adipose tissue sample from a single donor was incubated in triplicate, and leptin results are expressed as the mean +/- SEM of the integrated secretion to the medium (area under the curve; nanograms of leptin per g tissue/48 h). Control nonstimulated samples showed a steady leptin secretion along the 96 h studied, with the peak of secretory activity reached at 48 h; afterward, the in vitro secretion reached a plateau state. Spontaneous leptin secretion in samples from 33 women (3904 +/- 347) was significantly higher (P < 0.05) than that in samples from 34 men (2940 +/- 323). Coincubation of adipose tissue with 1 mumol/L dexamethasone induced a clear-cut leptin increase (P < 0.05) in samples from women (5848 +/- 624; n = 12), but did not change the spontaneous release of leptin in samples from men (3353 +/- 741; n = 6). Similarly, coincubation of adipose tissue with 1 mumol/L estradiol induced a notable leptin increase (P < 0.05) in samples from women (5698 +/- 688; n = 9), whereas it did not alter the secretion in the male samples (3373 +/- 444; n = 6). In samples from both sexes, coincubation with 1 mumol/L estrone or progesterone had no effect, whereas 1 mumol/L forskolin significantly (P < 0.05) reduced leptin release. In conclusion, leptin secretion from omental adipose tissue in vitro 1) is significantly higher in samples from women than in samples from men, 2) is stimulated by dexamethasone and estradiol in women but not in men, 3) is not modified by progesterone or estrone in both sexes, and 4) is inhibited by forskolin in both genders. This different response to the stimulation of adipose tissue may be the biological basis for the gender differences observed in circulating levels of human leptin.     

Initial trajectories of sensory axons toward laminar targets in the developing mouse spinal cord

Quantitative ultrasonic tissue characterization using backscattered high-frequency intravascular ultrasound could provide a basis for the objective identification of lesions in vivo. Representation of local measurements of quantitative ultrasonic parameters in a conventional image format should facilitate their interpretation and thus increase their clinical utility. Toward this goal, the apparent integrated backscatter, the slope of attenuation (25-56 MHz) and the value of the attenuation on the linear fit at 37.5 MHz were measured using the backscattered radio frequency signals from in vitro human aortae. Local estimations of these ultrasonic parameters from both normal and atherosclerotic aortic segments were displayed in a B-scan format. The morphological features of these parametric images corresponded well to features of histological images of the same regions. The attenuation from 25-56 MHz of seven segments of the medial layer (both with and without overlying atheroma) were measured using the multinarrow-band backscatter method. The average attenuation in the media at 24 degrees C +/- 3 degrees C was 45 +/- 16 dB/cm at 25 MHz and 102 +/- 13 dB/cm at 50 MHz. This work represents progress toward the development of quantitative imaging methods for intravascular applications.     

Reproduction function in mice exposed to neonatal irradiation

In colony-bred Wistar rats maintained for several weeks on a high-percent fatty food (fat content 50%) compared with controls (3% fat in food) the concentrations of the following lipids were determined quantitatively: In serum lipid phosphorus (Lip. P.), free fatty acids (FFA), triglycerides (TG), free cholesterole (FC) and cholesteryl ester (CE), in liver Lip. P,TG, FC and CE, in epididymal adipose tissue Lip. P. FFS and TG. With increasing weight differences between the two animals groups, in the phase of steady weight growth (,,dynamic phase", age of investigation 9 weeks, after 4 weeks on fatty food) a significant rise in serum FFS over the controls is observed with increases in TG and CE concentrations in the liver. After about 20 weeks of life the weight growth slows down; in this subsequent "static phase" the TG and CE accumulation in the liver further increases. Investigation of the epididymal adipose tissue suggests hypertrophy of the adipose cells. The results obtained with both phases are discussed with regard to possible metabolic alterations.     

Differential accumulation and release of long-chain n-3 fatty acids from liver, muscle, and adipose tissue triacylglycerols

Eicosapentaenoic acid (EPA, 20:5n-3) is less efficiently accumulated in tissue triacylglycerols (TAGs) during fish oil feeding than docosahexaneoic acid (DHA, 22:6n-3) or docosapentaenoic acid (DPA, 22:5n-3), and EPA is preferentially released from the TAG of isolated adipocytes in vitro and adipose tissue in vivo during fasting compared with DHA or DPA. It is not known if this preferential release occurs in vivo under nonfasting conditions or if it is limited to adipose tissue. Accordingly, we have carried out experiments to study the turnover of EPA, DHA, and DPA in the TAG of adipose tissue, liver, and skeletal muscle. Weanling rats were fed diets containing fish oil for 6 weeks and then switched to diets containing only corn oil as the dietary fat for 8 weeks. The fatty acid composition and mass in epididymal fat pads, omental fat, liver, and soleus muscle TAGs were determined weekly for the first 10 weeks and at weeks 12 and 14. Subsequent to the change to the corn oil diet, EPA (20:5n-3), DPA (22:5n-3), and DHA (22:6n-3), which had accumulated during fish oil feeding, were lost from the tissue TAG pools of each tissue examined. After 8 weeks on the corn oil diet, less than 10% of the accumulated EPA, DPA, and DHA remained in the liver and muscle. The loss of EPA, DPA, and DHA from epididymal fat pad was slower. In each tissue, EPA was lost more rapidly than DPA or DHA. This selective loss of EPA relative to DHA or DPA may explain the previously reported underrepresentation of EPA compared with DHA or DPA in tissue TAG.     

Fat distribution and insulin response in prepubertal African American and white children

Ethnic differences in obesity-related disease prevalence may relate to differences in fat distribution or metabolism. We conducted a study in 73 African American and white children to examine the relation between fat distribution and insulin and to determine whether ethnic differences in fat distribution or in adiposity-insulin relations contribute to differences in insulin concentrations. Fasting and postchallenge insulin concentrations were determined by oral-glucose-tolerance test, total body fat by dual-energy X-ray absorptiometry, and subcutaneous abdominal (SAAT) and intraabdominal (IAAT) adipose tissue by computerized tomography. African Americans had greater fasting insulin (x +/- SD: 79 +/- 37 compared with 55 +/- 23 pmol/L, P < 0.01), incremental 30-min insulin (567 +/- 438 compared with 300 +/- 304 pmol/L, P < 0.001), and incremental area under the insulin curve (AUC; 262 +/- 209 compared with 164 +/- 156 pmol/L, P < 0.01). In multiple linear regression, fasting insulin was independently related to total fat within both ethnic groups (model R2 = 0.42 and 0.52 for African Americans and whites, respectively), incremental 30-min insulin to total fat and IAAT in whites only (model R2 = 0.71), and AUC to SAAT in African Americans only (model R2 = 0.49). Adjusting insulin indexes for adiposity did not eliminate the significant effect of ethnicity. In general, relations between adiposity and insulin were stronger in whites than in African Americans. African American children had higher insulin concentrations than white children after total body fat, IAAT, and SAAT were controlled for. However, strong relations between adiposity (total and abdominal) and insulin in both groups suggest that obesity may contribute to disease risk regardless of ethnicity.     

Adipose tissue leptin production and plasma leptin kinetics in humans

Abdominal adipose tissue leptin production was determined in vivo by arteriovenous balance in 14 lean and obese men (mean BMI 27.0 +/- 1.9, range 21.4-45.2). Blood samples were taken simultaneously from an abdominal vein that drains subcutaneous adipose tissue and from a radial artery. Adipose tissue blood flow was measured by xenon washout. Abdominal vein leptin concentrations (mean 8.9 +/- 2.4 ng/ml, range 2.1-36.5 ng/ml) were consistently greater than arterial values (mean 6.6 +/- 1.9 ng/ml, range 1.7-28.2 ng/ml) (P < 0.001). The net rate of abdominal adipose tissue leptin production (mean 3.2 +/- 0.5 ng x 100 g(-1) x min(-1)) correlated directly with percentage body fat (rs = 0.59, P = 0.016). Estimated whole-body leptin production rate (797 +/- 283 ng x person(-1) x min(-1)) correlated directly with percent body fat (rs = 0.93, P < 0.0001) and with regional leptin production (rs = 0.81, P < 0.001). In contrast, the rate of leptin clearance from plasma (mean 1.50 +/- 0.23 ml x kg(-1) x min(-1)) and plasma leptin half-life (mean 24.9 +/- 4.4 min) was unrelated to adiposity (rs = 0.06, P = 0.30; rs = 0.16, P = 0.30, respectively). These results provide direct evidence that leptin is produced by adipose tissue in humans and that the rate of production is directly related to adiposity. A combination of greater leptin production per unit of body fat and increased production from expanded total body fat mass, rather than alterations in leptin clearance, account for the increase in plasma leptin concentrations observed in obese humans.     

Fat distribution and hemostatic measures in obese children

We examined the relation of general and visceral adiposity to plasma hemostatic factors [fibrinogen, D-dimer, and plasminogen activator inhibitor 1 (PAI-1)] in obese boys and girls 7-11 y of age (n = 41). Boys had significantly greater fibrinogen and D-dimer concentrations than girls (P < 0.05). whereas blacks had significantly greater fibrinogen and D-dimer concentrations than whites (P < 0.05). Univariate analyses revealed that fibrinogen was positively associated with percentage body fat (%BF) (r = 0.42, P < 0.01), subcutaneous abdominal adipose tissue (SAAT) (r = 0.40, P < 0.01), total fat mass (r = 0.42, P < 0.01), and body mass index (r = 0.41, P < 0.01). PAI-1 was positively associated with visceral adipose tissue (VAT) (r = 0.49, P < 0.01), SAAT (r = 0.32, P < 0.05), fat-free mass (r = 0.50, P < 0.01), and insulin (r = 0.61, P < 0.001). D-Dimer was positively associated with %BF (r = 0.40, P < 0.01), SAAT (r = 0.37, P < 0.05), total fat mass (r = 0.40, P < 0.01), and body mass index (r = 0.43, P < 0.01). Multiple regression analysis revealed that for fibrinogen, sex and higher %BF explained significant independent portions of the variance. For PAI-1, higher amounts of VAT and fat-free mass were significant predictors. For D-dimer, ethnicity was a significant predictor. These results suggest that general adiposity and VAT may play a role in regulating plasma hemostatic factors in obese children. Even early in childhood, adiposity is associated with unfavorable concentrations of hemostatic factors that are in turn implicated in cardiovascular morbidity and mortality later in life.     

Reliability of B-mode ultrasonic measurements of subcutaneous adipose tissue and intra-abdominal depth: comparisons with skinfold thicknesses

Adipose tissue deposits, particularly intra-abdominal adipose tissue, are associated with health risks such as diabetes mellitus and cardiovascular disease. Anthropometric techniques currently in use can measure subcutaneous adipose tissue (SAT) with skinfold calipers, but are limited to certain sites and cannot measure intra-abdominal adipose tissue (IAAT). Radiography, computerized tomography (CT) and magnetic resonance imaging (MRI) have been used, but they are expensive and some involve exposure to radiation. This study, which investigated the utility of B-mode ultrasound for measuring adipose tissue, found that ultrasonic measurements of SAT were as reliable as skinfold caliper measurements. Intra-observer and inter-observer coefficients of reliability for five of six ultrasonic measurements of SAT ranged from 91-98%, in comparison with coefficients of reliability ranging from 93-98% for three skinfold measurements. Coefficients of reliability for ultrasonic measurements of SAT at the paraspinal site were below 90%. Ultrasonic measurements of intra-abdominal depth (IAD), an index of IAAT, yielded an inter-observer coefficient of reliability of 64%. Ultrasound is recommended for measurement of subcutaneous adipose tissue but not for measurement of IAD.