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Influence of hyper- and hypothyroidism on subcutaneous adipose tissue blood flow in man.

Subcutaneous adipose tissue (AT) blood flow (BF) in the abdomen, thigh, and arm was determined by measuring the local clearance of [133]Xe in patients with untreated hyper- or hypothyroidism (n = 10, n = 7); six patients in each group were reexamined after treatment when they were euthyroid. Abdominal ATBF before treatment was 5.5 +/- 0.8 (SE) ml/min X 100 g AT in the hyperthyroid patients and 1.3 +/- 0.3 ml/min X 100 g AT in those who were hypothyroid. After therapy abdominal ATBF was 60% lower (P less than 0.05) in the hyperthyroid group and 80% higher (P less than 0.05) in the hypothyroid group. Similarly, ATBF in the thigh and arm was significantly reduced and increased, respectively, after treatment in the two groups. The blood glycerol level in the hyperthyroid group was 128 +/- 24 mumol/liter initially and was 50% lower (P less than 0.05) after therapy, whereas in the hypothyroid group blood glycerol levels were similar before (46 +/- 4 mumol/liter) and after therapy. Body fat, expressed as a percentage of body weight, was similar in the two groups before and after treatment. There was a positive correlation (P less than 0.001) between ATBF and serum T3 and T4 levels and an inverse correlation (P less than 0.01) between ATBF and plasma norepinephrine levels. Mean arterial blood pressure was similar in the two groups indicating that the alterations in ATBF were due to changes in vascular resistance. The results of this study suggest that thyroid hormones regulate sc ATBF in man.

Adipose Tissue↗

Assimilation of triglycerides in subcutaneous and intraabdominal adipose tissues in vivo in men: effects of testosterone.

To determine the effects of testosterone (T) on lipid assimilation in different adipose tissue depots, T (250 mg, im) was given to 17 middle-aged men 5 days before abdominal surgery. Twenty-four hours before surgery, 10 microCi labeled oleic acid in 80 g milk fat were administered orally. Lipid radioactivity was measured in adipose tissue biopsies from abdominal ac, omental, and retroperitoneal adipose tissues. Subcutaneous, visceral (omental plus mesenteric), and retroperitoneal adipose tissue masses were determined using computerized tomography scans at 22 levels. Sixteen men who were not treated with T served as controls. T administration was followed by an increase in serum concentrations from 17.7 +/- 1.1 to 32.6 +/- 1.8 nmol/L (P < 0.001) and a marked (> 50%) reduction compared with controls in lipid radioactivity in omental and retroperitoneal adipose tissues, but not in sc adipose tissue. In controls, sc, visceral, and retroperitoneal adipose tissues assimilated 59.2 g (73.4%), 16.9 g (20.9%), and 4.6 g (5.7%), respectively, of the orally administered fat. In the T-treated men, this was changed to 73.5 g (88.8%), 6.4 g (7.7%), and 2.9 g (3.5%), respectively. It was concluded that T inhibits triglyceride assimilation in intra-abdominal depots and apparently directs this lipid to sc fat in men.

Abdomen↗

Antepartum detection of macrosomic fetus: clinical versus sonographic, including soft-tissue measurements.

OBJECTIVE: To compare clinical and sonographic estimates of birth weights with five new estimation techniques that involve measurements of soft tissue, for identifying newborns with birth weights of at least 4000 g. METHODS: Over 1 year, each woman at or after 36 weeks' gestation and suspected of having a macrosomic fetus had clinical and sonographic estimates of fetal weight (EFW) based on femur length (FL) and head and abdominal circumference, followed by five additional ways to identify excessive growth: cheek-to-cheek diameter, thigh soft tissue, ratio of thigh soft tissue to FL, upper arm subcutaneous tissue, and EFW derived from it. Areas (+/- standard error) of receiver operating characteristic (ROC) curves were calculated and compared with the area under the nondiagnostic line. P <.05 was considered statistically significant. RESULTS: Among 100 women recruited, 28 newborns weighed 4000 g or more. The areas under the ROC curves with clinical (0.72 +/- 0.06) and sonographic predictions using biometric characteristics (0.73 +/- 0.06) had the highest but similar accuracies (P.05). Three of the five newer methods (upper arm or thigh subcutaneous tissue and ratio of thigh subcutaneous tissue to FL) were poor diagnostic tests (range of areas under ROC 0.52 +/- 0.06 to 0.58 +/- 0.07). Estimated fetal weight based on upper arm soft tissue thickness and cheek-to-cheek diameter (areas 0.70 +/- 0.06 and 0.67 +/- 0.06, respectively) were not significantly better than clinical predictions (P.05) for detecting macrosomic fetuses. About 110 macrosomic and nonmacrosomic infants combined would be needed to have 80% power to detect a difference between ROC curves with areas of 0.58 (thigh subcutaneous tissue) and 0.72 (clinical estimate). CONCLUSION: ROC curves indicated that measurements of soft tissue are not superior to clinical or sonographic predictions in identifying fetuses with weights of at least 4000 g.

Adult↗

Late skin and subcutaneous soft tissue changes after 10-gy boost for breast conserving therapy.

PURPOSE: To evaluate the influence of boost irradiation for breast conserving therapy on skin and subcutaneous tissue. MATERIALS AND METHODS: Between 1989 and 1995, 468 patients were treated with breast conserving surgery (quadrantectomy or wide excision with axillary dissection) followed by 50 Gy whole breast irradiation. Among them, fifty-eight patients with positive or close margins were treated with 10 Gy external beam boost irradiation. Skin and subcutaneous soft tissue changes during 5-years of follow-up were examined by inspection and palpation and evaluated using the BCT follow-up form based on EORTC late effect toxicity scoring. RESULT: Four percent (20/468) of the patients showed grade 2 late changes in skin and soft tissue. Four of them had skin telangiectasis, which was limited to within the boost field. Boost irradiation had no definite influence on other late changes. Patients' age, extent of surgery, and pT size had no significant relation to the late changes. The cosmetic score 5 years after BCT was not significantly different between the patients with and without boost irradiation. CONCLUSION: Although 10 Gy boost irradiation after 50 Gy whole breast irradiation increased skin telangiectasis, the late skin and soft tissue changes caused by the boost irradiation were generally mild and there was no substantial deterioration of cosmetic outcome.

Adenocarcinoma↗

The effects of soft tissue coverage on bone graft resorption in the craniofacial region.

Experiments were performed to study the amount of resorption of endochondral bone grafts in pockets covered by muscle tissue compared to pockets covered by subcutaneous tissue in immature rabbits at 16 weeks post-grafting. In the first group the grafts were used as onlays on the buccal surfaces of the mandible with cover by masseter on one side of the face and subcutaneous tissues on the other. The second experiment was similar but the grafts were fixed semi-rigidly with wiring. In the third the grafts were used as onlays on the cranium with muscle or subcutaneous tissue coverage. The fourth group of bone grafts were implanted into muscle and subcutaneous tissue pockets in the abdominal wall. Bone graft resorption was significantly greater when covered by muscle than by subcutaneous tissue. This effect is probably mediated by movement imparted to the graft by adjacent active muscle, and over-rides any benefits of increased vascularising potential muscle may have. Semi-rigid fixation offered no protection against this effect.

Animals↗

Familial lipoprotein lipase-activity deficiency: study of total body fatness and subcutaneous fat tissue distribution.

Total body fatness and subcutaneous fat tissue distribution were evaluated in 19 hyperchylomicronemic patients. Eleven were males, aged 10 to 57 years, and eight were females, aged 13 to 46 years. Familial lipoprotein-lipase-activity deficiency was diagnosed by the absence of lipoprotein-lipase activity in the plasma withdrawn ten and 20 minutes after intravenous injection of ten units of heparin per kilogram of body weight. The 19 patients had skin-fold measurements for evaluation of subcutaneous fat distribution. Fifteen also underwent body density measurements by underwater weighing. Percent body fat was calculated from body density. These anthropometric data were plotted against the regression curves of 1638 normal controls of both sexes (aged 10 to 54 years) for fat tissue weight, percent body fat, subcutaneous fat/total fat mass ratio and trunk/extremity skin-fold ratio. Impairments in the process of building fat tissue reserves could not be shown in the 19 hyperchylomicronemic patients, in spite of the absence of lipoprotein-lipase activity in their postheparin plasma. It is hypothesized that normal fat tissue mass in these patients could be due partly to de novo synthesis of fatty acids by adipocytes, hydrolysis of plasma triglycerides by hepatic lipase, and/or contribution of a specific fat-tissue lipase to the catabolism of plasma triglyceride-rich lipoproteins.

Adipose Tissue↗

Subcutaneous adipose tissue: a source of lactate production after glucose ingestion in humans.

The in vivo kinetics of lactate and pyruvate in the extracellular space of subcutaneous adipose tissue after glucose ingestion were investigated in healthy volunteers by the use of a microdialysis sampling technique. Comparison was made with the metabolite levels in venous plasma. The absolute subcutaneous tissue concentrations of lactate and pyruvate were estimated in the fasting state by perfusion with varying lactate- and pyruvate-containing solutions. An equilibrium with the surrounding extracellular fluid was found for both lactate and pyruvate in concentrations similar to those in venous plasma. After glucose ingestion there was an increase in the circulating levels of glucose, lactate, and pyruvate, which returned to base-line values within 3 h. There was a more marked increase in lactate in subcutaneous adipose tissue than in venous blood, and the adipose tissue lactate remained elevated for at least 3 h. In contrast, pyruvate levels increased much less in subcutaneous fat than in venous blood. The addition of isoproterenol (which inhibits adipose tissue glucose metabolism) to the tissue perfusate lowered the subcutaneous tissue lactate levels significantly but did not affect the subcutaneous pyruvate levels. These data suggest that human subcutaneous adipose tissue is a source of in vivo lactate production after glucose ingestion. Since lactate is thought to be a major substrate for glycogen synthesis in the liver, the present findings may provide evidence of a new and important role of the adipose tissue metabolism in the regulation of whole body glucose homeostasis in humans.

Adipose Tissue↗

Relationship between visceral fat, steroid hormones and insulin sensitivity in premenopausal obese women.

OBJECTIVES: The relationships between visceral fat distribution, steroid hormones and peripheral insulin sensitivity were studied. SETTING: All subjects were hospitalized in the Institute of Internal Medicine of the University of Verona, Italy. SUBJECTS: Nineteen fertile obese women were studied with ages ranging from 18 to 53 years and body mass indexes ranging from 27.3 to 48.4. INTERVENTION: Body fat distribution was evaluated by waist-to-hip circumference ratio and by computed tomography. The insulin tolerance test was used to evaluate peripheral insulin sensitivity. Glucose, insulin and C-peptide were measured in fasting conditions and during glucose load; total and free plasma testosterone and urinary cortisol excretion were also determined. RESULTS: Significant correlations emerged between visceral adipose tissue and fasting glucose, insulin, and C-peptide, but not between visceral adipose tissue and total testosterone, free testosterone or urinary cortisol excretion. A negative correlation emerged between visceral adipose tissue and insulin sensitivity (r = -0.70; P < 0.01). No significant correlations were found between insulin sensitivity and age, body weight, body mass index, total adipose tissue, subcutaneous adipose tissue or waist-to-hip ratio. Total testosterone correlated with body weight, subcutaneous adipose tissue and total adipose tissue. Free testosterone and urinary cortisol excretion correlated positively with body weight, and negatively with age. No correlation was found between insulin sensitivity and total testosterone, free testosterone or urinary cortisol excretion. The correlation between visceral adipose tissue and insulin sensitivity remained significant even after adjusting for both age and the body mass index. CONCLUSIONS: Our study shows that visceral fat is more closely associated with aberrations of insulin sensitivity than with obesity itself. Total testosterone, free testosterone and urinary cortisol excretion in our subjects do not seem to be associated with such aberrations.

Adipose Tissue↗

Blood flow in subcutaneous adipose tissue depends on skin-fold thickness.

Blood flow in subcutaneous adipose tissue is reduced in obese compared to lean subjects. Limitations in vascular supply might interfere with adipose tissue function as a metabolic and endocrine organ. We tested the hypothesis that nutritive blood flow and tissue metabolism depends on subcutaneous adipose tissue thickness even in normal-weight subjects. Sixteen young, healthy, normal-weight subjects (8 men, 8 women) were included in the study. Abdominal subcutaneous adipose thickness was assessed by skin-fold measurements. The microdialysis technique was applied for monitoring basal adipose tissue blood flow (ethanol dilution technique) and metabolism. An increase in skin-fold thickness from 15 to 45 mm and from 8 to 37 mm was associated with a linear increase in basal ethanol ratio from 0.19 to 0.63 and 0.25 to 0.75 and linear decreases in dialysate glucose concentrations from 1.95 to 0.24 mM and 1.68 to 0.29 mM, and 152 to 42 microM and 172 to 49 microM for glycerol concentrations in men and women, respectively (p < 0.05). Isoproterenol-stimulated blood flow also inversely correlated to skin-fold thickness (p < 0.05). We conclude that increased adipose tissue thickness is associated with reduced tissue perfusion and metabolism, even in lean subjects. Skin-fold thickness is an important confounding variable in metabolic studies, particularly in microdialysis experiments.

Adipose Tissue↗

Glycerol production in subcutaneous adipose tissue in lean and obese humans.

To estimate the regional subcutaneous glycerol production rate in normal and obese humans, the venous arterialized plasma glycerol, interstitial glycerol in the subcutaneous adipose tissue together with adipose tissue blood flow (ATBF, ml/100 g.min) were measured in the postabsorptive state and for 2 h after ingestion of 100 g of oral glucose. Eight lean and eight obese men with normal oral glucose tolerance tests were investigated with the subcutaneous microdialysis technique and 133Xe clearance. In the postabsorptive state, the interstitial glycerol concentrations in lean and obese subjects were 170 +/- 21 vs. 282 +/- 28 microM (P less than 0.01) and 156 +/- 23 vs. 225 +/- 12 microM (P less than 0.05) in the abdominal and femoral subcutaneous adipose tissue, respectively. The corresponding arterial glycerol levels were 54 +/- 4 vs. 75 +/- 14 microM (NS). Abdominal ATBF was greater in lean subjects (3.2 +/- 0.6 vs. 1.6 +/- 0.3; P less than 0.05), whereas femoral ATBF was similar in both groups (2.7 +/- 0.4 vs. 2.4 +/- 0.7). Estimated mean local glycerol release (mumol/100 g.min) was similar in the lean and obese group (0.16 +/- 0.03 vs. 0.20 +/- 0.05 and 0.18 +/- 0.02 vs. 0.17 +/- 0.04) in the abdominal and femoral site, respectively. We conclude that glycerol production from the subcutaneous tissue is increased in obesity, irrespective of adipose tissue distribution. This enhancement is due to the increased adipose tissue mass.

Adipose Tissue↗

Evidence for lactate production by human adipose tissue in vivo.

Microdialysis of the abdominal subcutaneous tissue was performed in seven healthy normal weight subjects after an overnight fast and also after oral ingestion of 100g glucose. The lactate concentration in the interstitial water was compared with that in the venous and arterialized plasma from the cubital veins. In the postabsorptive state the lactate concentration in the subcutaneous tissue (1128 +/- 72 mumol/l, mean +/- SEM) was significantly higher (p less than 0.01) than that in both arterialized (722 +/- 72 mumol/l) and venous plasma (798 +/- 41 mumol/l). The oral glucose load further increased the lactate level in the subcutaneous tissue throughout the observation period of 2h. The kinetics for the increase in the lactate concentration was not apparently different in blood or tissue. The highest lactate levels were 1798 +/- 173 mumol/l in the subcutaneous tissue and 1199 +/- 150 mumol/l and 1275 +/- 123 mumol/l in arterialized and venous plasma, respectively. It is concluded that abdominal adipose tissue produces lactate both in the fasting state and after an oral glucose load. The data emphasize the importance of the adipose tissue as a significant source of lactate production in the body.

Adipose Tissue↗

Engineering the tissue which encapsulates subcutaneous implants. III. Effective tissue response times.

The results of two previous studies have shown that implant porosity can be used to increase both the measured diffusion coefficients and the vascularity within the tissue encapsulating long-term subcutaneous implants. This study investigates the hypothesis that the analyte concentrations within the tissue surrounding porous implants will respond more quickly to changes in plasma levels than does the densely packed, avascular fibrous capsule surrounding nonporous implants. The average concentration of lissamine-rhodamine was measured in tissue within 100 microm of the following implants at four different times following injection of the tracer: PVA-skin, PVA-5, PVA-60, PVA-700 (polyvinyl alcohol nonporous, 5 microm, 60 microm, and 700 microm mean pore sizes, respectively) and PTFE-0.5 and PTFE-5 (polytetrafluoroethylene 0.5 microm and 5 microm mean pore sizes, respectively). The results were compared to those of unimplanted subcutaneous tissue (SQ). In addition, the data were analyzed with a simple two-compartment model in which a tissue response time constant (taup) was extracted. As in the case of vascular density, the cellular dimension of the PVA-60 pore sizes produced surrounding tissue with the optimum response times to changes in plasma concentrations. The concentrations of rhodamine within the tissue surrounding the PVA-60 implant were the highest at all time points and responded to the change in plasma rhodamine concentration approximately three times more quickly (taup = 764 s) than the fibrous tissue encapsulating the nonporous PVA-skin (taup = 2058 s) and more than twice as quickly as SQ (taup = 1627 s). The overall mass transfer rate between plasma and the tissue surrounding the different implants calculated from the permeability and density of vessels from the previous study correlated very well (r2 = 0.7, p < .02, slope of 0.98) with the reciprocal of the tissue response time constant (taup).

Animals↗

Comparative study of in vitro lipogenesis in various adipose tissues in the growing domestic pig (Sus domesticus).

Activities of acetyl-CoA-carboxylase, malic enzyme and glucose-6-phosphate-dehydrogenase were measured in seven different anatomical sites in the growing pig (20-120 kg weight). The three enzyme activities increased up to 40-60 kg weight and then decreased, malic enzyme becoming the main producer of NADPH, irrespective of the adipose tissue. Subcutaneous adipose tissue of the neck area was much thicker and exhibited much lower lipogenic enzyme activities than backfat. Subcutaneous adipose tissue is heterogeneous in the pig with some areas exhibiting very low lipogenesis and high lipid deposition importing triglycerides from other areas with high lipogenesis. However, these conclusions based on the measurement of enzyme activity potentials need to be confirmed with measurements of actual activities.

Acetyl-CoA Carboxylase↗

In vivo subcutaneous adipose tissue glucose kinetics after glucose ingestion in obesity and fasting.

The kinetic pattern of subcutaneous adipose tissue extracellular glucose following glucose ingestion was investigated in vivo with a microdialysis technique in normal-weight (n = 21) and obese subjects (n = 18) before and after a 7-day fast (n = 9). A dialysis probe (4 x 0.5 mm) was implanted subcutaneously, and was continuously perfused (5 microliters/min). The tissue dialysate glucose concentration was determined in 15-min samples before and during a period of 180 min after a 75-g oral glucose load. A comparison was made between the tissue dialysate concentrations and the venous blood glucose levels. In all study groups the increase in subcutaneous tissue dialysate glucose following glucose ingestion paralleled that in blood, with a time-lag of up to 15 min. In the normal-weight subjects the maximum relative increase in abdominal adipose tissue dialysate glucose was 25% higher (p less than 0.005) than the corresponding blood glucose level, and the total relative glucose level (area under curve, AUC) in abdominal fat was 20% (p less than 0.01) higher than in blood. In contrast, the kinetics of gluteal subcutaneous tissue dialysate and blood glucose levels were similar. In the obese patients before the fasting period the maximum relative glucose level in abdominal fat was almost twice as high as in blood (p less than 0.005), and the total glucose level (AUC) was 50% higher than the blood glucose AUC (p less than 0.005). After the fast, on the other hand, almost identical relative dynamics of abdominal subcutaneous tissue and blood glucose levels were found.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdomen↗

Intrinsic regulation of blood flow in adipose tissue.

Previous studies on intact human subcutaneous tissue have shown, that blood flow remains constant during minor changes in perfusion pressure. This so-called autoregulatory response has not been demonstrable in isolated preparations of adipose tissue. In the present study on isolated, denervated subcutaneous tissue in female rabbits only 2 of 12 expts. revealed an autoregulatory response during reduction in arterial perfusion pressure. Effluent blood flow from the tissue in the control state was 15.5 ml/100 g-min (S.D. 6.4, n = 12) corresponding to slight vasodilatation of the exposed tissue. Following total ischemia all experiments showed a period with reactive hyperemia, and both duration of hyperemia and excess flow was related to the duration of the ischemia. This response therefore seems more resistant to the experimental procedure, while autoregulation of blood flow to lowered pressure is more susceptible to surgical exposure of the tissue. During elevation of arterial perfusion pressure blood flow in the isolated tissue showed a transient increase and then almost returned to the level during normotension, indicating an elevated vascular resistance. Raising of venous pressure elicited vasoconstriction with pronounced flow reduction. These two reactions may be important for local regulation of blood flow in subcutaneous tissue during orthostatic changes in arterial and venous pressure. It is concluded that the response in adipose tissue to changes in arterial pressure (autoregulation), venous pressure and total ischemia appear to be elicited by different mechanisms.

Adipose Tissue↗

Lipid metabolism and cellular features of skeletal muscle and subcutaneous adipose tissue in pigs differing in IGF-II genotype.

In pigs, a paternally (pat) imprinted mutation in the IGF-II gene is associated with increased muscle mass and decreased backfat thickness. The aim of this study was to determine whether this mutation influenced cellular, biochemical and metabolic features of skeletal muscle and adipose tissue. Muscle (trapezius) and subcutaneous adipose tissue (SCAT) were collected from pigs (106kg) carrying (Qpat, n=6) or not carrying (qpat, n=7) the mutation. Adipocytes were isolated from those tissues by collagenase treatment. Lipid content and activity of lipogenic enzymes were determined using standard assays. Gene expression levels were determined by real-time PCR. Levels of IGF-II mRNA were higher (P<0.01) in muscle of Qpat than in that of qpat pigs, but they did not differ significantly between the two groups in SCAT. Whereas levels of IGF-I mRNA in muscle were similar in both groups, they were higher (P<0.05) in SCAT of Qpat pigs than in that of qpat pigs. Muscle lipid content and intramuscular adipocyte diameters were not influenced significantly by the IGF-II genotype. In SCAT, the reduction of backfat thickness in Qpat pigs compared with qpat pigs was associated with lower (P<0.05) lipid content and smaller (P<0.05) adipocytes, with no significant genotype-effects on expressions and/or activities of lipogenic enzymes. In summary, our results suggest that the IGF-II mutation altered body composition in pigs by favoring myofiber hypertrophy and repressing adipose cell development in SCAT.

Adipocytes↗