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Influence of adenosine on the vascular responses to sympathetic nerve stimulation in the canine subcutaneous adipose tissue.

Adenosine appears to regulate resting blood flow in canine subcutaneous adipose tissue. Sympathetic nerve stimulation has been shown to enhance the adenosine production in this tissue. This study therefore tested the possibility that adenosine may influence the vascular responses to sympathetic nerve stimulation. Intraarterial infusion of adenosine (5-20 microM in arterial blood) increased the resting vascular conductance (from 0.048 +/- 0.007 to 0.095 +/- 0.013 ml . min-1 . 100 g-1. mmHg-1) and the percental reduction in vascular conductance due to sympathetic nerve stimulation (4 HZ) by 34 per cent (p less than 0.05) and to i.a. noradrenaline by 27 per cent (p less than 0.05). The vasodilator response due to nerve stimulation after alpha-blockade was reduced by adenosine. Dipyridamole (0.5-1.5 microM) + EHNA (3-10 microM), which increases plasma adenosine levels, had similar effects to adenosine, while theophylline (30-80 microM) decreased the vasoconstrictor response. The vasoconstrictor escape was enhanced by EHNA alone and in combination with dipyridamole, but was reduced by theophylline. On the other hand, the poststimulatory hyperemia was unaffected by adenosine, dipyridamole and EHNA, and theophylline. The results show that adenosine does not reduce the magnitude of the initial vasoconstrictor response in proportion to the increase in resting blood flow. The autoregulatory escape in adipose tissue during nerve stimulation appears to be mediated both by adenosine and by noradrenaline acting on beta-adrenoceptors. Poststimulatory hyperemia does not seem to be greatly influenced by exogenous or endogenous adenosine.

Adenine↗

Total forearm blood flow as an indicator of skeletal muscle blood flow: effect of subcutaneous adipose tissue blood flow.

1. In studying forearm skeletal muscle substrate exchange, an often applied method for estimating skeletal muscle blood flow is strain gauge plethysmography. A disadvantage of this method is that it only measures total blood flow through a segment of forearm and not the flow through the individual parts such as skin, adipose tissue and muscle. 2. In the present study the contribution of forearm subcutaneous adipose tissue blood flow to total forearm blood flow was evaluated in lean (% body fat 17.0 +/- 2.2) and obese males (% body fat 30.9 +/- 1.6) during rest and during infusion of the non-selective beta-agonist isoprenaline. Measurements were obtained of body composition (hydrostatic weighing), forearm composition (magnetic resonance imaging) and of total forearm (venous occlusion plethysmography), skin (skin blood flow, laser Doppler), and subcutaneous adipose tissue blood flow (133Xe washout technique). 3. The absolute forearm area and the relative amount of fat (% of forearm area) were significantly higher in obese as compared to lean subjects, whereas the relative amounts of muscle and skin were similar. 4. During rest, the percentage contribution of adipose tissue blood flow to total forearm blood flow was significantly higher in lean compared with obese subjects (19 vs 12%, P < 0.05), whereas there were no differences in percentage contribution between both groups during isoprenaline infusion (10 vs 13%). Furthermore, the contribution of adipose tissue blood flow to total forearm blood flow was significantly lower during isoprenaline infusion than during rest in lean subjects (P < 0.05), whereas in the obese this value was similar during rest and during isoprenaline infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗

Local metabolic changes in subcutaneous adipose tissue during intravenous and epidural analgesia.

BACKGROUND: This clinical study aimed at investigating the impact of postoperative thoracic epidural analgesia on extracellular glycerol concentration and glucose metabolism in subcutaneous adipose tissue, using the microdialysis technique. The sympathetic nervous activity, which can be attenuated by epidural anesthesia, influences lipolysis and the release of glycerol. METHODS: Fourteen patients who underwent major abdominal or thoraco-abdominal surgery were studied postoperatively over 3 days. For postoperative analgesia the patients were prospectively randomized to receive either thoracic epidural analgesia with a bupivacaine/morphine infusion (EPI-group, n=6) or a continuous i.v. infusion of morphine (MO-group, n=8). The concentration of glycerol, glucose and lactate in the abdominal and deltoid subcutaneous adipose tissue were measured using a microdialysis technique. RESULTS: The abdominal glycerol levels were equal in both groups. In the deltoid region of the EPI-group, glycerol concentrations started to increase on Day 2, and reached significantly higher levels on Day 3 compared with the MO-group. The glucose and lactate levels showed no differences between groups in the two regions. CONCLUSION: The uniform glycerol levels in abdominal subcutaneous adipose tissue in conjunction with the difference in glycerol levels in the deltoid area indicate that the local lipolysis is different in the two study groups. This might be explained by a regional metabolic influence of thoracic epidural analgesia, possibly via the sympathetic nervous system.

Adipose Tissue↗

Association of fatty liver with increased ratio of visceral to subcutaneous adipose tissue in obese men.

We studied the association of fatty liver with subcutaneous and visceral obesity in 46 male and 36 female patients with body mass index (BMI) over 22 kg/m2. The correlation coefficient between the ratio of the visceral adipose tissue to the subcutaneous adipose tissue (V/S) and the computed tomography (CT) number of the liver was -0.299 (P < 0.05) and that between the V/S ratio and the ratio of the CT number of the liver to that of the spleen (CT-L/CT-S) was -0.335 (P < 0.05) in the males. Partial correlation analysis after making correction for BMI showed an increased correlation coefficient of -0.485 (P < 0.05) between the V/S ratio and the CT-L/CT-S ratio in the males. The odds ratio in the males for CT-L/CT-S below 1.0 and V/S above 1.0 was 3.25 with a 95% confidence interval of 1.02 to 9.39. No such association between the V/S ratio and the CT-L/CT-S ratio was present in the female patients. Multiple regression analysis with serum level of alanine aminotransferase, a marker of fatty liver, as an independent variable revealed a partial regression coefficient of -17.7 for CT-L/CT-S (P < 0.05) in the males and -21.7 (P < 0.05) in the females, validating the CT-L/CT-S ratio as an index of fatty liver. The results indicate the association of fatty liver as determined by the CT-L/CT-S ratio with visceral obesity in males.

Adipose Tissue↗

Thermogenic response to epinephrine in the forearm and abdominal subcutaneous adipose tissue.

Whole body energy expenditure, thermogenic and metabolic changes in the forearm, and intercellular glucose concentrations in subcutaneous adipose tissue on the abdomen determined by microdialysis were measured during epinephrine infusion in healthy subjects. After a control period, epinephrine was infused at rates of 0.2 and 0.4 nmol.kg-1 x min-1. Whole body resting energy expenditure was 4.36 +/- 0.56 (SD) kJ/min. Energy expenditure increased to 5.14 +/- 0.74 and 5.46 +/- 0.79 kJ/min, respectively (P < 0.001), during the epinephrine infusions. Respiratory exchange ratio was 0.80 +/- 0.04 in the resting state and did not change. Local forearm oxygen uptake was 3.9 +/- 1.3 mumol.100 g-1 x min-1 in the basal period. During epinephrine infusion, it increased to 5.8 +/- 2.1 (P < 0.03) and 7.5 +/- 2.3 mumol.100 g-1 x min-1 (P < 0.001). Local forearm glucose uptake was 0.160 +/- 0.105 mumol.100 g-1 x min-1 and increased to 0.586 +/- 0.445 and 0.760 +/- 0.534 mumol.100 g-1 x min-1 (P < 0.025). The intercellular glucose concentration in the subcutaneous adipose tissue on the abdomen was equal to the arterial concentration in the basal period but did not increase as much during infusion of epinephrine, indicating glucose uptake in adipose tissue in this condition. If it is assumed that forearm skeletal muscle is representative for the average skeletal muscle, it can be calculated that on average 40% of the enhanced whole body oxygen uptake induced by infusion of epinephrine is taking place in skeletal muscle. It is proposed that adipose tissue may contribute to epinephrine-induced thermogenesis.

Abdomen↗

Glycogen content in subcutaneous adipose tissue of newborns of different birth weights in the first week of life.

The glycogen content of the subcutaneous adipose tissue was examined in 164 newborns of different birth weights. It amounted to 0.48 +/- 0.05 mg glycogen/g wet weight on average and did not depend on the weight of the newborn, week of gestation in the 38th to 41st week of pregnancy and duration of labor. In small-for-date newborns the glycogen content per gram wet weight was equal to the eutrophic and large-for-date newborns. The amount of fat tissue and also the total glycogen content in small-for-date newborns, however, is substantially lower. The glycogen content decreases in the first hours of life. It reaches the lowest values at 24-48 h of life. This bears witness to the quick depletion of glycogen reserves of the subcutaneous adipose tissue. The different amounts of carbohydrate and fat reserves stress the importance of early nutrition in some groups of newborns, especially of low-birth-weight newborns.

Adipose Tissue↗

Expression of adipogenic transcription factors, peroxisome proliferator-activated receptor gamma co-activator 1, IL-6 and CD45 in subcutaneous adipose tissue in lipodystrophy associated with highly active antiretroviral therapy.

OBJECTIVE: To determine the expressions of multiple genes in the subcutaneous adipose tissue of HIV-positive, highly active antiretroviral therapy (HAART)-treated patients with and without lipodystrophy. DESIGN AND METHODS: Real-time polymerase chain reaction was used to measure gene expressions in this cross-sectional study. RESULTS: The messenger RNA concentrations of adipose transcription factors (peroxisome proliferator-activated receptor (PPAR) gamma and delta and sterol regulatory element binding protein 1c) were all significantly lower in the lipodystrophic than the non-lipodystrophic group. The mRNA concentration of PPAR-gamma co-activator 1 (PGC-1), which regulates mitochondrial biogenesis, was lower in the lipodystrophic than the non-lipodystrophic group. The mRNA expression of lipoprotein lipase, acyl coenzyme A synthase and glucose transport protein 4 were significantly lower in the lipodystrophic than the non-lipodystrophic group, but the mRNA concentrations of fatty acid transport and binding proteins were similar in both groups. The mRNA concentrations of IL-6 and CD45 (a common leukocyte marker) were significantly higher in the lipodystrophic than the non-lipodystrophic group. CONCLUSION: Multiple alterations characterize gene expression in the subcutaneous adipose tissue of patients with HAART-associated lipodystrophy compared with HIV-positive, HAART-treated patients without lipodystrophy. The low expression of transcription factors inhibits adipocyte differentiation. The low expression of PGC-1 may contribute to mitochondrial defects. In addition, IL-6 and CD45 expressions are increased, the latter implying an excessive number of cells of leukocyte origin in lipodystrophic adipose tissue. Mitochondrial injury and an excess of proinflammatory cytokines may lead to increased apoptosis. All these changes may contribute to the loss of subcutaneous fat in HAART-associated lipodystrophy.

Actins↗

Identification of progesterone receptor in human subcutaneous adipose tissue.

Sex steroids are postulated to play a role in adipose tissue regulation and distribution, because the amount and location of adipose tissue changes during puberty and menopause. Because of the nature of adipose tissue, receptors for the female sex steroids have been difficult to demonstrate. To date, estrogen receptor messenger RNA and protein have been identified in human subcutaneous adipose tissue, but the presence of progesterone receptor (PR) has not been reported. In this study, we demonstrate PR message by Northern blot analysis in RNA isolated from the abdominal subcutaneous adipose tissue of premenopausal women. These preliminary studies revealed that PR messenger RNA levels are higher in the stromal-vascular fraction as opposed to the adipocyte fraction. Western blot analysis demonstrates both PR protein isoforms (human PR-A and human PR-B) in human subcutaneous adipose tissue. Using an enzyme-linked immunosorbent assay, total PR could be quantitated. These studies substantiate that sex steroid receptors are present in human adipose tissue, thereby providing a direct route for regulation of adipose tissue by female sex steroids.

Abdomen↗

Comparison of the fatty acid composition of subcutaneous adipose tissue from mature Brahman and Hereford cows.

The fatty acid composition of adipose tissue was measured in 37 mature Brahman and 32 mature Hereford cows to determine breed effect. Diet was held constant among all cows. When biopsied, cows were on oats and native cool-season annual pastures of good quality. Real-time ultrasound measurements of subcutaneous fat were taken at three locations (between the 12th and 13th rib, at the rump, and at the perianal region) to determine overall fatness. Overall fat thickness from these measurements was 1.3 cm for Brahman cows and 1.7 cm for Hereford cows (P < .01). Subcutaneous adipose tissue biopsy samples were collected from the perianal region, and fatty acid composition was determined using a gas chromatograph. Fatty acids were expressed in both normalized (area percentage) and gravimetric (grams/100 grams of fresh tissue) formats. In addition to greater overall subcutaneous fat thickness, Hereford cows contained 5 g more of fatty acids per 100 g of fresh adipose tissue than Brahman cows (P < .05). Subcutaneous adipose tissue from Hereford cows was higher (P < .01) in total saturated fatty acids and lower in mono- and polyunsaturated fatty acids than subcutaneous adipose tissue from Brahman cows. Compositional differences remained when breeds were compared by analysis of covariance at a common body fatness. The data suggest a genetic basis for the differences in fatty acid composition of Brahman and Hereford cows.

Adipose Tissue↗

Tissue oxygenation and perfusion in patients with systemic sepsis.

OBJECTIVE: Multiple organ dysfunction is associated with systemic sepsis. To investigate whether this is attributable to peripheral tissue hypoperfusion and/or cellular hypoxia, simultaneous measurements of tissue perfusion and oxygenation were made in patients with severe sepsis and in controls. DESIGN: Prospective, observational study. SETTING: Adult intensive care unit, tertiary referral center. PATIENTS: Volunteers (group C, n = 7), patients undergoing cardiopulmonary bypass (group B, n = 6), and patients with severe sepsis (group S, n = 6). INTERVENTIONS: Limb ischemia and reperfusion. MEASUREMENTS AND MAIN RESULTS: Tissue oxygenation and microvascular flow were measured by using microelectrodes inserted into brachoradialis muscle and overlying subcutaneous tissue. Forearm cutaneous red cell flux and regional blood flow were measured simultaneously. Responses to 20 mins of limb ischemia and subsequent reperfusion were observed. Baseline muscle tissue oxygenation was greater in sepsis (1.7 +/- 0.2, 1.5 +/- 0.7, and 4.4 +/- 0.6 kPa for groups C, B, and S, respectively, mean +/- sem, p <.05), although baseline subcutaneous tissue oxygenation did not vary between groups. During ischemia tissue oxygenation, values decreased in muscle (to 1.3 +/- 0.2, 1.0 +/- 0.4, and 1.5 +/- 0.4 kPa for groups C, B, and S, respectively) and subcutaneous tissue (to 2.0 +/- 0.3, 1.7 +/- 0.5, and 2.3 +/- 0.2 kPa for groups C, B, and S, respectively). Decline in tissue oxygen tension was initially more rapid in septic muscle compared with controls (25% decrease, 68 +/- 23 vs. 176 +/- 38 for group S vs. group C, p <.05, and 50% decrease, 126 +/- 34 vs. 398 +/- 72 secs for group S vs. group C, p <.01). However, overall rate of tissue decline was similar (95% decrease, 444 +/- 122 vs. 614 +/- 96 for group S vs. group C, p >.05). After reperfusion, significant differences in muscle tissue oxygenation reappeared between groups (2.0 +/- 0.3, 1.5 +/- 0.7, and 4.0 +/- 0.4 kPa for groups C, B, and S, respectively, p <.05). There were no differences in time to 25%, 50%, or 95% tissue oxygen recovery. Whole limb reperfusion was significantly less in patient groups compared with controls (10.6 +/- 0.9, 4.5 +/- 1.2, and 4.3 +/- 1.6 mL x 100 mL(-1) x min(-1) for groups C, B, and S, respectively, p <.05). CONCLUSIONS: Significant differences in tissue oxygenation distribution between muscle and subcutaneous tissues occur in patients with severe sepsis. High baseline muscle tissue oxygen levels are accompanied by rapid extraction of oxygen during stagnant ischemia.

Adult↗

Irradiation-induced hypoxia in bones and soft tissues: an experimental study.

Bone marrow and subcutaneous tissue pO2 and pCO2 were measured by means of implanted tissue tonometers in irradiated and nonirradiated rabbit hind limbs. The x-ray dose was 500, 1000, 1500, 2000, and 3000 rads. Tissue gas tensions were measured 1 day and 5 and 11 weeks after radiation. The pCO2 changes in both tissues were slight but not statistically significant. The subcutaneous tissue pO2 decreased during the acute phase of irradiation injury, and the effect of irradiation was dose-dependent. Later on, irradiation had no significant effects on the subcutaneous pO2, although light microscopy of the affected tissues showed fibrosis and blood vessel changes. The response of the subcutaneous pO2 to systemic hyperoxia also increased in the chronic phase of irradiation injury as a sign of improved microcirculation. The bone marrow showed a high radiosensitivity. Irradiation caused a rapid dose-dependent decrease of the marrow pO2, and the marrow pO2 decreased with time during the chronic phase of irradiation injury. The marrow pO2 responded slowly and marginally to an increment of arterial pO2 during breathing 100% oxygen as further evidence of impaired vascular pattern. The results showed that irradiation causes only a transient impairment of tissue perfusion in the skin. However, irradiation-damaged marrow was characterized by progressive tissue hypoxia.

Animals↗

Delta9 desaturase activity in bovine subcutaneous adipose tissue of different fatty acid composition.

Two experiments were conducted to investigate the relationship between delta9 desaturase (stearoyl-coenzyme A desaturase) activity and fatty acid composition in subcutaneous adipose tissue from cattle of different backgrounds. In Experiment 1, subcutaneous adipose tissue samples were taken from carcasses of pasture-fed cattle and feedlot cattle fed for 100, 200, or 300 d. Adipose tissue from pasture-fed cattle had significantly lower total saturated fatty acids and higher total unsaturated fatty acids than feedlot cattle. Desaturase activity correspondingly was 60-85% higher in pasture-fed cattle than in feedlot cattle. There was no difference in the fatty acid composition or desaturase activity among samples from the 100-, 200-, and 300-d feedlot cattle. In Experiment 2, adipose tissue samples were collected from carcasses of feedlot cattle fed for 180 d with either a standard feedlot ration (control group), or a ration containing rumen-protected cottonseed oil (CSO) for the last 70-80 d. Adipose tissue from the CSO-fed cattle was more saturated than that from the control group, having significantly more 18:0 and less 16:1 and 18:1. Correspondingly, adipose tissue from the CSO group had significantly lower desaturase activity. The elevated 18:2 in adipose tissue from the CSO group confirmed that unsaturated fatty acids (including cyclopropenoid fatty acids) were protected from biohydrogenation. Further studies are needed to determine whether the repression of desaturase activity results from direct inhibition by cyclopropenoic acids or by higher dietary contents of 18:2.

Adipose Tissue↗

[Coplanar PCBs, PCDFs and PCDDs in the subcutaneous adipose tissue of Yusho patients and normal controls].

3,4,3',4'-tetrachlorobiphenyl (T4CB), 3,4,5,3',4'-pentachlorobiphenyl (P5CB) and 3,4,5,3',4',5'-hexachlorobiphenyl (H6CB) [Co-PCBs] in the subcutaneous adipose tissue of seven Yusho patients and eight normal controls were determined to assess the contribution in the risk caused by the Yusho causual agents (PCBs, PCDFs, PCDDs and Co-PCBs) by using high resolution gas chromatography/high resolution mass spectrometry in selected ion monitoring mode. 3,4,3',4'-T4CB, 3,4,5,3',4'-P5CB and 3,4,5,3',4',5'-H6CB were detected in the subcutaneous adipose tissue of the Yusho patients at the levels, of 6 to 29 ppt, of 32 to 130 ppt and of 160 to 1,140 ppt, respectively. The TCDD-Eq (Equivalents) value calculated by TCDD-TEfs (Toxic Equivalent factors) was from 8 to 30 ppt. On the other hand, 3,4,3',4'-T4CB, 3,4,5,3',4'-P5CB and 3,4,5,3',4',5'-H6CB were detected in the subcutaneous adipose tissue of normal controls at the levels, of 3 to 9 ppt, of 41 to 280 ppt and of 47 to 200 ppt, respectively. The TCDD-Eq value calculated by TCDD-TEfs was from 9 to 57 ppt. In the Yusho patients, the average TCDD-Eq value calculated by TCDD-TEfs of the residual Co-PCBs, PCDFs and PCDDs was 17, 491 and 24 ppt, respectively. Therefore, we concluded that the typical symptoms for the Yusho patients are caused mostly by PCDFs.

Adipose Tissue↗

Deep dermatofibrosarcoma protuberans: a subcutaneous variant.

AIMS: Dermatofibrosarcoma protuberans (DFSP) is a distinctive cutaneous spindle cell neoplasm that invariably infiltrates the subcutaneous tissue. Other reports have suggested that exceptional cases of DFSP may be confined to the subcutaneous tissue and lack dermal involvement. We wish to confirm this observation by describing cases of a rare variant of DFSP confined to the subcutaneous tissue, and analyse possible histogenetic implications. METHODS AND RESULTS: Three cases of DFSP located in the subcutaneous tissue are reported. Multiple step sections demonstrated the lack of dermal involvement in two of them, whereas the third case infiltrated the dermis at the junction with the subcutis minimally in one of five blocks. Immunohistochemical studies using a battery of monoclonal antibodies were performed. All the tumours stained strongly for vimentin and CD34. CONCLUSIONS: Because of the lack of dermal involvement in two cases and only minimal dermal involvement in one case, we called this variant deep DFSP. Except for deep setting of the tumour, deep DFSP is indistinguishable from typical DFSP clinically, histologically and immunohistochemically. The existence of deep DFSP provides evidence that specific structures of the skin may be not involved in this tumour's histogenesis.

Adult↗

Effects of acipimox on the lipolysis rate in subcutaneous adipose tissue of obese subjects.

BACKGROUND: Acipimox is a hypolipidaemic agent reducing serum concentrations of triglycerides and non-esterified fatty acids. Acipimox may reduce triglyceride synthesis by decreasing non-esterified fatty acid availability from adipocytes, but this effect has yet to be demonstrated in vivo. Lipolysis after acipimox treatment was examined in subcutaneous adipose tissue of severely obese subjects with associated metabolic disorders. METHODS: The microdialysis technique was performed in abdominal subcutaneous adipose tissue of eight hyperinsulinaemic subjects. After oral treatment with acipimox, glycerol concentration was determined as an index of lipolysis rate. Blood flow was assessed by the ethanol escape technique. The rates of release of glycerol from human adipose tissue maximally stimulated by norepinephrine were also investigated in the presence of acipimox. Eight weight- and age-matched subjects served as a control group. RESULTS: Under acipimox treatment, basal glycerol release decreased in subcutaneous adipose tissue, whereas no effect was observed on blood flow. In stimulated adipose tissue acipimox showed no effect. CONCLUSION: In the present study basal glycerol outflow from adipose tissue was inhibited by acipimox. The anti-lipolytic action of the agent may diminish elevated plasma concentrations of free fatty acids in subjects with severe obesity.

Adipose Tissue↗

Mitochondrial DNA decrease in subcutaneous adipose tissue of HIV-infected individuals with peripheral lipoatrophy.

OBJECTIVE: To determine whether the peripheral fat wasting (lipodystrophy), which is seen in association with highly active antiretroviral therapy (HAART) that includes a nucleoside reverse transcriptase inhibitor (NRTI), is associated with a decrease in subcutaneous adipose tissue mitochondrial DNA (mtDNA) content or with large mtDNA deletions or insertions. DESIGN: A four cohort cross-sectional study. METHODS: The mtDNA content of subcutaneous fat tissue from the neck, abdomen and thigh was determined by polymerase chain reaction utilizing the amplification of three different mtDNA fragments. The results from HIV-infected patients with peripheral fat wasting following more than 6 months of NRTI-containing HAART were compared with the results from three different control cohorts: HIV-infected patients with a similar treatment history without lipodystrophy; HIV-infected patients naive to antiretroviral therapy and HIV sero-negative participants. RESULTS: A decrease in mtDNA content was found in HAART-treated HIV-infected patients with peripheral fat wasting in comparison with subjects in the control cohorts. No large mitochondrial deletions or insertions were found. CONCLUSIONS: Lipodystrophy with peripheral fat wasting following treatment with NRTI-containing HAART is associated with a decrease in subcutaneous adipose tissue mtDNA content.

Adipose Tissue↗

Net carbon flux across subcutaneous adipose tissue after a standard meal in normal-weight and insulin-resistant obese subjects.

OBJECTIVE: To elucidate the alterations in subcutaneous adipose tissue metabolism in obesity which affect substrate storage in the fed state, by describing as completely as possible the 'metabolic balance sheet' for adipose tissue. SUBJECTS: 13 lean people (age: 24-64 years, BMI: 19.3-29.4 kg/m2) and 9 insulin-resistant obese subjects (age: 38-57 years, BMI: 32.4-56.0 kg/m2). MEASUREMENTS: Net flux of eight major substrates and CO2 across subcutaneous adipose tissue in vivo before and after eating a standard mixed meal (3.1 MJ, 41% from fat). RESULTS: The net flux of total carbon atoms in the 8 substrates and CO2 was negative (net export from the tissue) in both groups in the fasting state. After the meal it changed rapidly to a positive balance (net substrate storage) in the control group and remained positive until 5 h, whereas in the obese group it remained negative throughout. The overall carbon balance in adipose tissue reflected predominantly the movement of fatty acids in and out of the tissue. CONCLUSIONS: The fact that fat storage failed to occur despite elevated plasma concentrations of triacylglycerol, glucose and insulin indicates an alteration in metabolic regulation at the cellular level which might be called insulin resistance. Insulin resistance of fat metabolism may be an adaptation which limits further fat deposition, but is maladaptive in terms of risk factors for atherosclerosis.

Adipose Tissue↗

Effects of dipyridamole and theophylline on reactive hyperaemia in subcutaneous adipose tissue in humans.

The importance of adenosine for reactive hyperaemia in subcutaneous adipose tissue was studied in healthy volunteers, using the adenosine uptake inhibitor dipyridamole (bolus 0.1 mg/kg i.v. followed by infusion of 0.7 microgram/kg/min) and the adenosine receptor antagonist theophylline (4 or 6 mg/kg i.v.). Basal blood flow, total blood flow and hyperaemia (total minus basal flow) after a 20-min arterial occlusion were measured in the distal femoral region by the 133Xe washout technique with and without drug treatment. Basal blood flow (mean +/- SEM) was 2.4 +/- 0.3 ml/min/100 g, while total post-occlusive flow and total reactive hyperaemia were 97.3 +/- 8.4 and 61.8 +/- 6.5 ml/100 g, respectively, without drug treatment. Basal blood flow was unaffected by dipyridamole but the total flow and hyperaemia were enhanced by 49 +/- 24 and 60 +/- 31%, respectively (P less than 0.05 for both). This enhancement was due to increases in both amplitude and duration of the hyperaemia. Neither basal blood flow, total post-occlusive flow nor hyperaemia were significantly altered by theophylline. The amplitude of the enhanced hyperaemia during dipyridamole was not significantly counteracted by simultaneous theophylline treatment (6 mg/kg) but the duration of hyperaemia was reduced from 13 +/- 1 to 8 +/- 1 min (P less than 0.01). The results suggest that endogenous adenosine does not regulate basal blood flow or reactive hyperaemia of limited duration in human adipose tissue. However, reactive hyperaemia may be enhanced by pharmacological elevation of endogenous adenosine levels.

Adenosine↗