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Subcutaneous adipose tissue expression of tumour necrosis factor-alpha is not associated with whole body insulin resistance in obese nondiabetic or in type-2 diabetic subjects.

BACKGROUND: An association with subcutaneous adipose tissue TNFalpha expression and insulin resistance has been suggested in obesity/type-2 diabetes, but this has not been examined directly. In the first part of the study we investigated whether this association is present in 7 lean, 10 obese nondiabetic and 9 type-2 diabetic men. In the second part of the study we examined the relationship between adipose tissue TNFalpha mRNA levels and BMI in 81 nondiabetic subjects spanning a wide range of BMIs. METHODS: Subcutaneous adipose tissue TNFalpha mRNA levels and insulin sensitivity were determined with quantitative RT-competitive PCR and hyperinsulinaemic clamp, respectively. RESULTS: Subcutaneous adipose tissue TNFalpha mRNA levels were similar in 7 lean and 10 obese nondiabetic and 9 type-2 diabetic men (P = 0.68), and did not change in response to 240-min hyperinsulinaemia. TNFalpha mRNA levels and insulin sensitivity were not correlated. Unexpectedly, no correlation between TNFalpha mRNA and BMI was found. The relationship between adipose tissue TNFalpha mRNA and BMI was examined further in 31 male and 50 female nondiabetic subjects. The subcutaneous adipose tissue TNFalpha mRNA level correlated with BMI in all subjects (rS = 0.32, P < 0.01), and in a subgroup analysis in men (rS = 0.55, P < 0.01) but not in women (rS = - 0.08). The correlation in men was dependent on a fourfold higher TNFalpha mRNA level in 5 morbidly obese men while there was no difference in TNFalpha mRNA levels in lean or obese men. CONCLUSIONS: Subcutaneous adipose tissue TNFalpha expression does not correlate with insulin sensitivity in nondiabetic or type-2 diabetic men; is not regulated by acute hyperinsulinaemia; and is increased only in morbidly obese men.

Adipose Tissue↗

Relationship between serum and free interstitial concentrations of cefodizime and cefpirome in muscle and subcutaneous adipose tissue of healthy volunteers measured by microdialysis.

Microdialysis is a suitable method to monitor unbound concentrations of antimicrobial drugs in the interstitial tissue space which is the site of many infections. The aim of this investigation was to examine whether free tissue levels of cefodizime (81% plasma protein binding) and cefpirome (10% plasma protein binding) in muscle and subcutaneous adipose tissue of healthy volunteers obtained by microdialysis are consistent with the extent of their respective plasma protein binding. Healthy volunteers were given cefodizine and cefpirome at a single intravenous 2-g dose in a randomized crossover design. Microdialysis probes were inserted into a medial vastus muscle and into the periumbilical subcutaneous layer. After calibration of the probe, samples of serum and microdialysis fluid were obtained and drug concentrations were measured using a microagar diffusion-bioassay. There was a reasonable agreement between plasma protein binding data and the tissue penetration of both cephalosporins (AUC0-infinity tissue, free/AUC0-infinity serum, total-ratios) into the interstitial fluid of the muscle tissue, but not for the subcutaneous tissue layer. Furthermore, the serum and tissue concentrations of both drugs were fitted to an open two-compartment body model. The measured free-tissue concentrations were compared with calculated unbound concentrations in the peripheral compartment. Good agreement was observed for the free muscle concentrations, but unbound concentrations in the subcutaneous tissue was somewhat higher (cefpirome) or lower (cefodizime) than predicted. This may be due to the different lipophilicities of the two compounds.

Adipose Tissue↗

A reduced protein diet induces stearoyl-CoA desaturase protein expression in pig muscle but not in subcutaneous adipose tissue: relationship with intramuscular lipid formation.

A reduced protein diet (RPD) is known to increase the level of intramuscular lipid in pig meat with a smaller effect on the amount of subcutaneous adipose tissue. This might be due to tissue-specific activation of the expression of lipogenic enzymes by the RPD. The present study investigated the effect of a RPD, containing palm kernel oil, soyabean oil or palm oil on the activity and expression of one of the major lipogenic enzymes, stearoyl-CoA desaturase (SCD) and on the level of total lipids and the fatty acid composition of muscle and subcutaneous adipose tissue in pigs. The RPD significantly increased SCD protein expression and activity in muscle but not in subcutaneous adipose tissue. The level of MUFA and total fatty acids in muscle was also elevated when the RPD was fed, with only small changes in subcutaneous adipose tissue. A positive significant correlation between SCD protein expression and total fatty acids in muscle was found. The results suggest that an increase in intramuscular but not subcutaneous adipose tissue fatty acids under the influence of a RPD is related to tissue-specific activation of SCD expression. It is suggested that the SCD isoform spectra in pig subcutaneous adipose tissue and muscle might be different.

Acetyl-CoA Carboxylase↗

Continuous glucose monitoring in interstitial subcutaneous adipose tissue and skeletal muscle reflects excursions in cerebral cortex.

Continuous glucose monitoring (CGM) is being explored using several types of glucose sensors. Some are designed for subcutaneous adipose tissue. It is important to determine to which extent these glucose fluctuations in different tissues reflect changes taking place in the central nervous system, where glucose sensing is thought to occur. We studied the ability of subcutaneous adipose interstitial fluid measurements to parallel glucose propagations in blood, muscle, and central nervous system (CNS) during hyper- and hypoglycemia. A subcutaneous CGM system was applied in the CNS, subcutaneous adipose tissue, and skeletal muscle of nine Vietnamese potbellied pigs, and data were compared with frequent sampling in blood. Alterations in glucose levels were induced with intravenous glucose and insulin. During hyperglycemia, no difference was detected in delay between blood and interstitial glucose levels in subcutaneous adipose tissue (18.0 +/- 0.8 min), muscle (18.0 +/- 0.9 min), and CNS (20.3 +/- 1.2 min), respectively. During hypoglycemia, we found no time difference between interstitial parameters in the three tissues. However, the amplitude of glucose changes varied considerably, with a smaller magnitude of glucose change taking place in the brain. The timing of glucose excursions in subcutaneous adipose tissue and muscle reflect excursions in CNS. The reduced magnitude of glucose excursions in the brain suggests that different mechanisms of glucose transport are operative in CNS compared with subcutaneous adipose tissue and muscle.

Adipose Tissue↗

Measurement of subcutaneous adipose tissue topography (SAT-Top) by means of a new optical device, LIPOMETER, and the evaluation of standard factor coefficients in healthy subjects.

The quantification of obesity in respect to subcutaneous adipose tissue and fat distribution is a matter of interest. We recently reported on a new optical device, LIPOMETER, and its ability to measure the thickness of subcutaneous adipose tissue and its advantages compared with other methods. To describe the subcutaneous adipose tissue distribution of the human body in a precise, reproducible, and comparable manner, 15 well-defined body sites distributed from neck to calf on the right body side were used. This set of sites defines subcutaneous adipose tissue topography (SAT-Top). To visualize SAT-Top for subjects or groups, special SAT-Top plots were used. Subcutaneous adipose tissue distribution can be recognized easily with these techniques. SAT-Top of 590 healthy men and women was measured. Factor analysis was used to extract the essential information from these 590*15 intercorrelated single measurements and to provide standard factor coefficients for later applications. As an example of how to use the results of factor analysis, the strong SAT-Top deviation of women with clinically proven type-2 diabetes mellitus (NIDDM) from healthy controls is described. Am. J. Hum. Biol. 12:231-239, 2000. Copyright 2000 Wiley-Liss, Inc.

Journal Article↗

Tissue response to a new methacrylate-based root canal sealer: preliminary observations in the subcutaneous connective tissue of rats.

Silicone tubes filled with EndoRez, a methacrylate-based root canal sealer, were implanted in the subcutaneous connective tissue of the rat. Solid, silicone rods of the same size as the tubes also were implanted and used as negative controls. The tissue reaction to test and control materials was histologically studied and analyzed by elemental electron-microprobe analysis. After 10, 30, 90, and 120 days of implantation, different grades of tissue reaction to the tested materials were recorded. A granulomatous tissue containing numerous polymorphonuclear leukocytes, lymphocytes, and plasmocytes, as well as macrophages and foreign-body giant cells with engulfed material in their cytoplasm, was initially observed in contact with EndoRez. Fibroblasts and newly formed vessels also were observed. This cellular profile persisted after 30 days. The severity of the reaction decreased with time, and connective tissue healing was observed at the 120-day observation period, even though some specimens exhibited a slight, persistent, inflammatory cell infiltration. The electron-microprobe analysis of the tissues revealed the presence of heavy components of EndoRez in all observation periods. In contact with the controls, there was an initially slight concentration of inflammatory cells. This reaction rapidly subsided after 30 days, and a fibrous connective tissue encapsulation, free of inflammatory cells, could be observed at the 90- and 120-day observation periods.

Animals↗

Expression of nitric oxide synthases in subcutaneous adipose tissue of nonobese and obese humans.

Studies have shown evidence of production of nitric oxide (NO) in adipose tissue, as well as inhibition of lipolysis by NO. We have analyzed nitric oxide synthase (NOS) expression in subcutaneous adipose tissue from 13 nonobese and 18 obese male subjects. Using a competitive reverse transcription polymerase chain reaction method, endothelial (eNOS) and inducible (iNOS), but not neuronal (nNOS), nitric oxide synthase mRNA expression was detected in isolated fat cells and pieces of adipose tissue. Tissue mRNA levels for eNOS were 3,814 +/- 825 and 5,956 +/- 476 amol/mg RNA (P = 0.043), and for iNOS 306 +/- 38 and 332 +/- 48 amol/mg RNA, for nonobese and obese individuals, respectively. Western blotting revealed similar eNOS protein levels in isolated fat cells and adipose tissue pieces. Protein levels for eNOS in nonobese and obese individuals, respectively, were (in optical density [OD] units per mm(2) per 100 microgram of total protein) 0.11 +/- 0.08 and 2.80 +/- 1.30 (P = 0.043). iNOS protein was detectable, but not measurable, at low levels in a subset of obese patients (3 of 10). iNOS protein levels could not be detected in nonobese individuals. Hormone-sensitive lipase (HSL), the key regulating enzyme in lipolysis, is reduced in obesity. The expression of HSL protein in subcutaneous adipose tissue was studied in the same subset of patients; in agreement with previous results, HSL levels were reduced in obese subjects: 4.64 +/- 1.10 and 1.27 +/- 0.35 (P = 0.012) in nonobese and obese subjects, respectively. In conclusion, this study shows that eNOS and iNOS, but not nNOS, are present in human subcutaneous adipose tissue. Gene expression and protein levels of eNOS are increased, whereas HSL protein levels are decreased in obesity. It is speculated that increased NO production, preferably by eNOS, and decreased HSL levels may cause decreased subcutaneous adipose tissue lipolysis in obesity. synthases in subcutaneous adipose tissue of nonobese and obese humans.

Adipose Tissue↗

The distribution of oedema in the lower limb of patients with chronic critical limb ischaemia: a study with computed tomography.

BACKGROUND: A substantial number of patients with chronic critical limb ischaemia (CLI) have considerable oedema at the distal leg and foot of non deep venous thrombosis origin. The primary aim of the present study was to quantify the distribution of oedema in the different tissues of the leg and foot by applying computed tomography and planimetry. The interstitial fluid hydrostatic pressure (Pif) in the subcutaneous tissue was measured to evaluate the effect of oedema on local tissue pressure. PATIENTS AND METHODS: Six men and 12 women with unilateral CLI and peripheral pitting oedema were included. Cross sectional areas (CSA) of subcutaneous tissue, muscle and bone were measured by computer tomography combined with planimetry to assess the distribution of oedema within the soft tissues. Pif was measured by "wick-in-needle" technique. RESULTS: The median total CSA of soft tissue, subcutaneous and muscle tissues at the foot level were respectively 17%, 34% and 9% greater in the limbs with CLI compared to the contralateral limb (p < 0.001). At ankle level these differences were 13%, 30% and 4%, respectively (p < 0.001). At the level of the calf these differences were not significant. Mean Pif in the limbs with CLI was 0.3 mmHg, significantly higher than in limbs without CLI (-1.8 mmHg), (p < 0.003). CONCLUSION: The study verified oedema of considerable magnitude at the ankle and foot. The great part of the oedema was located within the subcutaneous tissue, which was associated with a relatively moderate, but significant increase in Pif confirming the high compliance of the subcutaneous tissue. The combination of the excessive fluid and increased Pif in the interstitial tissue might aggravate the microcirculation. The aetiology of oedema formation is probably multifactorial.

Aged↗

Comparative distribution of Baker's antifolate (NSC 139105) in rat tissues after subcutaneous and intravenous injections.

The tissue distribution of BAF was compared by intravenous and subcutaneous injections in rats bearing Walker 256 carcinoma. Following a single dose (6 mg/kg containing 30 microCi 4,6-di-14C-BAF), the drug concentrations were determined by radiochemical and dihydrofolate reductase assays. The two methods gave comparable results. No metabolites were found by paper chromatographic separations.

Animals↗

Subdivision of the subcutaneous adipose tissue compartment and lipid-lipoprotein levels in women.

OBJECTIVE: The aim of this study was to compare the relative importance of computed tomography-measured abdominal fat compartment areas, including adipose tissue located posterior to the subcutaneous Fascia, in predicting plasma lipid-lipoprotein alterations. RESEARCH METHODS AND PROCEDURES: Areas of visceral as well as subcutaneous deep and superficial abdominal adipose tissue were measured by computed tomography in a sample of 66 healthy women, ages 37 to 60 years, for whom a detailed lipid-lipoprotein profile was available. RESULTS: Strong significant associations were observed between visceral adipose tissue area and most variables of the lipid-lipoprotein profile (r = -0.25, p < 0.05 to 0.62, p < 0.0001). Measures of hepatic lipoprotein synthesis such as very-low-density lipoprotein-triglyceride and cholesterol content as well as total and very-low-density lipoprotein-apolipoprotein B levels were also strongly associated with visceral adipose tissue area (r = 0.57, 0.57, 0.61, and 0.62, respectively, p < 0.0001). Significant associations were found between these variables and the deep subcutaneous adipose tissue area or DXA-measured total body fat mass. However, the correlation coefficients were of lower magnitude compared to those with visceral adipose tissue area. Multivariate regression analyses demonstrated that visceral adipose tissue area was the strongest predictor of lipid-lipoprotein profile variables (7% to 48% explained variance, 0.02 > or = p < or = 0.0001). DISCUSSION: Although previous studies have generated controversial data as to which abdominal adipose tissue compartment was more closely associated with insulin resistance, our results suggest that visceral adipose tissue area is a stronger correlate of other obesity-related outcomes such as lipid-lipoprotein alterations.

Adipose Tissue↗

Effect of subcutaneous pancreatic tissue transplants on streptozotocin-induced diabetes in rats. I. Morphological studies on normal, diabetic and transplanted pancreatic tissues.

The present study examines the morphological changes occurring in subcutaneous pancreatic tissue grafts (SPTG) and its effect on the host pancreatic islet cells in streptozotocin (STZ)-induced diabetic rats using morphological techniques. SPTG survived after 15 weeks of transplantation. Its acinar cells degenerated but the ducts and endocrine cells survived. The surviving and newly formed pancreatic tubules and endocrine cells filled the spaces left by degenerated acinar cells. Compartmentalization of the surviving parenchymatic tissues was observed, with the pancreatic tubules lying in the periphery of the graft and the endocrine tissue in the inner portion of the graft. Lymphocytes invaded the inner portion of the graft, conglomerating around endocrine cells. It was interesting, however, that, lymphocytes where not observed in the periphery of the grafts where most of the surviving pancreatic tubules lie. In addition to this, necrotic tissues were observed in the inner part of the graft. Fifteen weeks after transplantation into the subcutaneous region, insulin, glucagon, somatostatin and pancreatic polypeptide-immunoreactive cells were observed in many parts of the graft. In the peripheral parts of the grafts, large numbers of pancreatic tubules differentiated into endocrine cells. In conclusion, the ductal and endocrine cells of pancreatic tissue fragments survived in the subcutaneous region of rat with normal pattern of distribution.

Animals↗

Differences in beta-adrenergic receptor densities in omental and subcutaneous adipose tissue from obese African American and Caucasian women.

African American women lose less weight and at a slower rate than Caucasian women under the same weight loss conditions. This is likely due to decreased mobilization of fat, possibly involving differences in the responsiveness of adipose tissue to adrenergic stimulation. To better understand the causes behind the decreased lipolysis in African American women, this study was initiated to determine if there were differences in the numbers and affinities of beta adrenoreceptors in omental and subcutaneous adipose tissue of obese African American and Caucasian women. We determined the number of beta receptors using a nonselective antagonist and found the total number of receptors in both omental and subcutaneous adipose tissue preparations were higher in African American than Caucasian women. beta(1)(,) beta(2), and beta(3) densities were higher in omental adipose tissue (P <.05), but not different in the subcutaneous tissue of the African American women. No racial differences in kd values for adrenergic agents (agonists and antagonists) were found with regard to beta(1), beta(2), or beta(3) receptors in either the omental or the subcutaneous preparations. beta(1) and beta(2) receptor protein (mass) was significantly increased in African American omental tissue preparations, but not subcutaneous. Our in vitro data demonstrating increased beta receptor numbers in omental tissue from obese African Americans suggest that the potential for lipolysis would be higher in these women. Future studies should determine the biologic significance of the differences in the beta adrenergic receptors in vivo.

Adipose Tissue↗

[Absence of lipolytic action of adrenaline on a human subcutaneous adipose tissue. Role of alpha-adrenergic receptors].

Epinephrine cannot stimulate adipocytes' lipolysis of human subcutaneous adipose tissue (lateral part of the thigh) while a clear lipolytic action can be shown on the omental tissue. However, at the same concentrations, isoproterenol (a beta-agonist) exerts a strong adipokinetic effect on adipocytes of the both types of adipose tissue. An alpha-adrenolytic (phentolamine) enhances the lipolytic action of epinephrine on the omental adipose tissue and unmasks a lipolytic action of epinephrine on the subcutaneous. Epinephrine antagonizes the lipolysis induced by theophyline on the subscutaneous adipocytes, this action is increased by propranolol (a beta-adrenergic blocking agent). The unresponsiveness to epinephrine of the subcutaneous adipose tissue studied here could be linked to a strong antilipolytic alpha-adrenergic effect.

Adipose Tissue↗

[Comparative levels of amphotericin B in the skin and subcutaneous fatty tissue after cutaneous application of amphotericin ointment by phonophoresis and with preliminary treatment by dimethyl sulfoxide].

A comparative study of the amphotericin B contents in the skin and subcutaneous fatty tissue was performed on guinea pigs after local application of amphotericin ointment by phonophoresis and with preliminary treatment of the skin by dimethyl sulfoxide (DMSO). When the amphotericin ointment was used in combination with ultrasound the content of amphotericin B in the skin and subcutaneous fatty tissue 1, 3, 24, 48 and 72 hours after the application was much higher than that after the ointment local application without the ultrasonic treatment. When the amphotericin ointment was applied locally after the preliminary treatment with DMSO the maximum content of the antibiotic in the skin and subcutaneous fatty tissue was observed 3 hours after the application which was significantly higher than the content observed after the ointment application by phonophoresis and especially locally without the ultrasonic treatment. In 24, 48 and 72 hours the amphotericin B concentration in the skin and subcutaneous fatty tissue under any conditions lowered and in 24 hours had a tendency to level in the areas treated with ultrasound and DMSO. In 48 and 72 hours the highest concentrations of the antibiotic were in the skin and subcutaneous fatty tissue after the ointment application by phonophoresis.

Adipose Tissue↗

[Fat of the subcutaneous adipose tissue in spontaneous panniculitisi (Weber-Christian disease)].

Histochemical investigations of fat in nodes of lesions of the subcutaneous fatty tissue in 25 patients with spontaneous panniculitis were carried out. It was shown that the disease was not accompanied by accumulation in the subcutaneous fatty tissue of such lipids as cholesterol, phosphoglycerides or glycolipids. Changes in triglycerides with formation of fatty acids were observed in fatty cells already in the presence of a developed cellular reaction in the subcutaneous fatty tissue and apparently could not be considered as a trigger mechanism in pathogenesis of spontaneous panniculitis. The revealing of aldehydes and lipids in fatty cells and in lipophages may indicate to an oxidative character of the processes developing in fat in spontaneous panniculitis. A suggestion is put forward that in pathogenesis of panniculitis a certain role could be played by an impairment of oxidation processes of fat with excessive accumulation of peroxides of lipids.

Adipose Tissue↗

Modification of subcutaneous adipose tissue by a methylxanthine formulation: a double-blind controlled study.

BACKGROUND: Excessive subcutaneous adipose tissue is typically treated by physically removing the fat through liposuction, but cost and accessibility have popularized alternative treatments for reducing adipose tissue thickness. OBJECTIVE: The purpose of this study was to test the absolute and relative effectiveness of a liposome-encapsulated caffeine-based cream in modifying subcutaneous adipose tissue. METHODS: Forty-one patients consented and completed the double-blind, single-center, placebo-controlled study. Caliper measurements, tape measurements, and photographs were taken over a 2-month period. RESULTS: Both concentrations of the cream were found to significantly reduce the thickness of the adipose tissue in all areas of the body. In addition, the more concentrated cream was significantly more effective than the less concentrated cream in the areas of the hips and the triceps. CONCLUSION: The caffeine-based liposome-encapsulated cream significantly reduced the thickness of the subcutaneous fat over a 2-month period.

Adipose Tissue↗

Tissue response to an experimental calcium hydroxide-based endodontic sealer: a quantitative study in subcutaneous connective tissue of the rat.

Silicone tubes containing a freshly mixed experimental Sealapex, in which titanium dioxide was removed from the original formula, were implanted in the dorsal subcutaneous connective tissue of the rat. Solid silicone rods of the same size as the tubes were also implanted and used as inert controls. The tissue reaction to both these materials was histometrically and quantitatively studied under light microscopy and by elemental electron microprobe analysis. After 7, 30 and 90 d of implantation, different grades of tissue reaction to the tested materials were recorded. A granulomatous tissue containing numerous foreign-body giant cells and macrophages with engulfed particles in their cytoplasms was initially detected in contact with the test material. In addition, many fibroblasts and newly formed vessels were also observed at these areas. The results of this study revealed that these reactions increased progressively at the 30- and 90-d observations. The electron microprobe analysis of the granulomatous tissues showed the presence of heavy components of the experimental material.

Animals↗

Subcutaneous adipose tissue blood flow and triacylglycerol-mobilization during prolonged exercise in dogs.

In 6 dogs concentration differences for glycerol and FFA were measured between the aorta and the external pudendal vein, a vein which mainly drains subcutaneous adipose tissue in dogs, during prolonged exercise. It was found that the a-v differences increased about 2-fold for both glycerol and FFA, however great interindividual differences were found. In 4 dogs adipose tissue blood flow, glycerol and FFA a-v differences were measured simultaneously, and the mobilizations of glycerol and FFA as well as the re-esterification of FFA were calculated. After 2 h of exercise the values were in the range of 1-7 umol/(100 g.min) for FFA and glycerol mobilizations while the FFA re-esterification was in the range of 2-14 umol/(100 g.min). It was found that the FFA/albumin ratio in adipose venous blood, on average 3.6 was at a level at which the FFA mobilization has been shown to depend on the adipose tissue blood flow in isolated fat pads. In 11 dogs subcutaneous adipose tissue blood flow rose 2-fold during exercise from about 5-10 ml/(100 g.min). It is concluded that the subcutaneous adipose tissue blood flow response to exercise is equal in man and dog, that lipolysis, FFA mobilization and FFA re-esterification are increased in subcutaneous adipose tissue during exercise, and that the increase in blood flows is of importance for the enhanced FFA mobilization during exercise.

Adipose Tissue↗