RESUMO
Oedema is a common finding in obesity and its cause is not always clear. Possible causes include impairment of cardiac, respiratory and/or renal function, chronic venous insufficiency and lymphatic problems. Lymphoscintigraphy is the best method to detect structural lymphatic abnormalities that can cause lymphoedema. We reviewed 49 female subjects with pitting oedema who had undergone lymphoscintigraphy, divided in three groups. The first group was comprised of severely obese patients in whom cardiorespiratory causes for oedema had been excluded. The second group consisted of non-obese patients with recognized causes for oedema and the third group was non-obese patients with 'idiopathic' oedema. A standard classification was used to interpret lymphoscintigraphy results. The frequency and severity of lymphoscintigraphic abnormalities was greatest in patients with clinical diagnoses of oedema related to 'recognized causes' (any abnormality in 50% of legs with obstruction in 22%). Obese patients and those with 'idiopathic'oedema had fewer (P=0.02 for both) and milder lymphoscintographic abnormalities (any abnormality 32 and 25%, respectively, obstruction 5 and 3%, respectively), and although the clinical oedema was invariably bilateral, the lymphoscintigraphy abnormalities were usually unilateral. In conclusion, structural lymphoscintigraphic abnormalities are uncommon in obesity and do not closely correlate with the clinical pattern of oedema.
Assuntos
Anormalidades Linfáticas/diagnóstico por imagem , Linfedema/etiologia , Linfocintigrafia , Obesidade/complicações , Adulto , Feminino , Humanos , Linfedema/diagnóstico por imagem , Masculino , Obesidade/diagnóstico por imagemRESUMO
Very little is known about the regulation of protein metabolism in adipose tissue. In this study systemic, adipose tissue, and forearm phenylalanine kinetics were determined in healthy postabsorptive volunteers before and during a 2-h glucose infusion (7 mg.kg-1.min-1). [3H]Phenylalanine was infused and blood was sampled from a radial artery, a subcutaneous abdominal vein, and a deep forearm vein. Adipose tissue and forearm blood flow were measured with 133Xe and plethysmography, respectively, and body fat mass was determined by dual energy x-ray absorptiometry. During glucose infusion, glucose concentration increased from 86 +/- 2 to 228 +/- 13 mg/dl and insulin concentration increased from 6.6 +/- 0.6 to 35.0 +/- 3.9 mU/liter, both P < 0.001. Systemic phenylalanine appearance decreased from 40.3 +/- 1.9 to 37.0 +/- 1.6 mumol/min during glucose infusion (P < 0.05). Baseline whole body adipose tissue phenylalanine release (5.2 +/- 1.4 mumol/min) was approximately 12% of systemic phenylalanine appearance and decreased (P < 0.05) to 2.3 +/- 0.9 mumol/min during glucose infusion. In contrast, phenylalanine release from the forearm did not change during glucose infusion. These results indicate that adipose tissue is a small but significant contributor to systemic phenylalanine appearance. Phenylalanine release from adipose tissue like lipolysis, is relatively sensitive to hyperinsulinemia.
Assuntos
Tecido Adiposo/metabolismo , Fenilalanina/farmacocinética , Adulto , Glucose/farmacologia , Humanos , MasculinoRESUMO
Insulin resistance has been proposed as the metabolic basis of atherogenesis. This hypothesis is based on the concept of the "insulin resistance syndrome," according to which insulin resistance is viewed as the primary abnormality that gives rise to dyslipidemia, essential hypertension, impaired glucose tolerance, and NIDDM. However, this hypothesis takes no account of the well-established and central role of vascular endothelium in the atherogenic process. Although endothelial injury is an early and prominent feature of atherogenesis, relatively little attention has been given to its metabolic consequences. In subjects with NIDDM, we have shown that endothelial dysfunction is associated with insulin resistance, raising the question of whether this relationship could be causal. In this article, we review the factors that are considered to be responsible for the development of endothelial dysfunction during atherogenesis, together with the metabolic consequences of endothelial dysfunction. While dysfunction of the endothelium in large and medium-sized arteries plays a central role in atherogenesis, we argue that dysfunction of peripheral vascular endothelium, at arteriolar and capillary level, plays the primary role in the pathogenesis of both insulin resistance and the associated features of the insulin resistance syndrome. We propose that the insulin resistance syndrome, together with many aspects of atherogenesis, can be viewed as the diverse consequences of endothelial dysfunction in different vascular beds. This new and testable hypothesis accounts for both the endothelial and metabolic abnormalities associated with atherogenesis.
Assuntos
Arteriosclerose/etiologia , Endotélio Vascular/fisiopatologia , Resistência à Insulina , Insulina/fisiologia , Animais , Arteriosclerose/fisiopatologia , Humanos , Hipercolesterolemia/fisiopatologia , Fumar/fisiopatologiaRESUMO
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.
Assuntos
Tecido Adiposo/anatomia & histologia , Tecido Adiposo/fisiologia , Biossíntese de Proteínas , Proteínas/metabolismo , Abdome , Tecido Adiposo/irrigação sanguínea , Adulto , Idoso , Índice de Massa Corporal , Humanos , Cinética , Leptina , Masculino , Pessoa de Meia-Idade , Obesidade , Radioimunoensaio , Fluxo Sanguíneo Regional , Análise de RegressãoRESUMO
Plasma leptin exists in protein-bound and free forms, which may affect its hormonal bioactivity. Therefore, the relationship between bound and free leptin may be particularly important during physiological conditions that cause rapid alterations in total plasma leptin concentration, such as fasting. The purpose of this study was to evaluate the effect of short-term fasting on bound and free plasma leptin concentrations and leptin binding capacity (a measure of plasma leptin-binding protein content) in lean and obese women. Six lean (body mass index, 21 +/- 1 kg/m2) and 6 abdominally obese (BMI, 36 +/- 1 kg/m2) women were studied after 14 h and 22 h of fasting. Although total plasma leptin concentration was more than 6-fold greater in obese (45.4 +/- 7.6 microg/liter) compared with lean (7.4 +/- 1.0 microg/liter) women at 14 h of fasting (P < 0.05), the percentage of leptin in the bound form was greater in lean than obese subjects (29 +/- 2% vs. 12 +/- 3%; P < 0.05). Arterial total, free, and bound plasma leptin concentrations all declined between 14 h and 22 h of fasting in both lean and obese groups, but the relative decline of these fractions was greater in lean (36 +/- 4%, 60 +/- 9%, and 51 +/- 13%, respectively) than in obese (19 +/- 5%, 21 +/- 8%, and 12 +/- 7%, respectively) subjects (all P < 0.05). In contrast, leptin binding capacity was unchanged. The percentage of total plasma leptin present in bound form was constant between 14 h and 22 h of fasting in lean subjects and increased slightly but significantly in obese subjects. These data demonstrate that both free and bound fractions of leptin in plasma decrease quickly in response to energy restriction, but the decline is blunted in abdominally obese compared with lean women. In addition, the equilibrium between bound and free leptin fractions is maintained during brief fasting and is not regulated by leptin binding capacity.
Assuntos
Leptina/sangue , Obesidade/sangue , Magreza/sangue , Absorciometria de Fóton , Tecido Adiposo/anatomia & histologia , Adulto , Peso Corporal , Jejum , Feminino , Humanos , Artéria Radial , Radioimunoensaio , Valores de Referência , Análise de Regressão , VeiasRESUMO
Leptin, the protein product of the ob gene, may be involved in the regulation of energy balance. Although a clear relationship between energy intake and plasma leptin concentrations has been demonstrated in humans, little is known about the effect of exercise on leptin metabolism. In the present study, we evaluated abdominal adipose tissue leptin production in vivo by arteriovenous balance at rest and during 60 min of moderate-intensity cycle ergometer exercise (50% of maximal heart rate) in five sedentary male subjects (mean age 38.4 +/- 1.7 yr, body mass index (28.4 +/- 4.2 kg/m2). Blood samples were taken simultaneously from an abdominal vein, draining sc adipose tissue, and a radial artery, at rest and every 10 min during exercise. Adipose tissue blood flow was determined by the xenon washout technique. Plasma leptin concentrations did not change throughout exercise and were the same as the values obtained during resting conditions. Average net adipose tissue leptin production rates during exercise (3.07 +/- 0.89 ng/100 g-1.min-1) also were similar to resting values (3.86 +/- 0.95 ng/100 g-1.min-1). These results demonstrate that plasma leptin concentrations and leptin production do not change during an acute bout of moderate-intensity aerobic exercise.
Assuntos
Tecido Adiposo/metabolismo , Exercício Físico , Proteínas/metabolismo , Adulto , Exercício Físico/fisiologia , Humanos , Leptina , Masculino , Fatores de TempoRESUMO
The sympathetic nervous system regulates lipolysis. There are regional differences in the sensitivity of lipolysis to adrenergic regulation. Little is known about regional sympathetic activity in response to eating in humans. We studied the effect of feeding on systemic and local sympathetic nervous system activity and lipolysis in lean healthy subjects (three women and five men; age, 27.0+/-2.0; body mass index, 23.4+/-1.2 kg/m(-2)) using isotope dilution methodology and arterio-venous sampling. Feeding increased arterial norepinephrine (NE) concentration (mean premeal, 0.96+/-0.12 nmol/L x L; mean postmeal, 1.28+/-0.14 nmol/L x L; P < 0.02) and total body NE spillover (mean premeal, 2.11+/-0.30 nmol/min x L; mean postmeal, 2.76+/-0.31 nmol/min x L; P < 0.02), whereas the arterial epinephrine concentration decreased (mean premeal, 289+/-61 pmol/L; mean postmeal, 170+/-5 pmol/L; P < 0.02). Palmitate concentration and total body systemic rate of appearance of palmitate declined postprandially (mean premeal, 117 +/- 15 micromol/min; mean postmeal, 38+/-4 micromol/min; P < 0.01). NE spillover increased by the same proportion in both forearm and adipose tissue [in forearm, mean premeal and postmeal, 1.02+/-0.11 and 2.41+/-0.44. nmol/100 mL x min, respectively (P < 0.02); in adipose tissue, mean premeal and postmeal, 0.41+/-0.12 and 0.73+/-0.17 nmol/100 g x min, respectively (P < 0.02)]. The results show that a meal caused differential changes in systemic sympatho-adrenal activity and an increase in sympathetic activity in adipose tissue postprandially, However, this increase in postprandial sympathetic activity was not enough to overcome the inhibition of lipolysis by insulin.
Assuntos
Tecido Adiposo/inervação , Norepinefrina/metabolismo , Período Pós-Prandial/fisiologia , Pele/inervação , Sistema Nervoso Simpático/fisiologia , Adulto , Feminino , Antebraço/inervação , Humanos , Lipólise , MasculinoRESUMO
Adipose tissue lipolysis is at least in part stimulated by the sympathetic nervous system (SNS). Although there is a generalized decrease in SNS activity with fasting, the rate of lipolysis during fasting increases. The aim of this study was to determine whether there is an association between activation of sympathetic nerves innervating adipose tissue and the increase in lipolysis seen during fasting in humans. We used the isotope dilution technique to measure regional norepinephrine spillover from abdominal sc adipose tissue from seven healthy subjects before and after a 72-h fast. Our results showed a significant increase in adipose tissue spillover of norepinephrine (mean +/- SEM, 0.40 +/- 0.09 vs. 1.08 +/- 0.18 pmol.100 g(-1).min(-1), P < 0.05) and arterial norepinephrine concentrations (0.92 +/- 0.10 vs. 1.23 +/- 0.08 nmol.liter(-1), P < 0.05) after the fast with no significant change in total body norepinephrine spillover, forearm norepinephrine spillover, epinephrine concentrations, or energy expenditure. We show for the first time, in humans, a selective regional increase in adipose tissue norepinephrine spillover in response to a 72-h fast and suggest that the SNS may play a greater role in the regulation of lipid metabolism during fasting than previously thought.
Assuntos
Tecido Adiposo/metabolismo , Jejum/metabolismo , Norepinefrina/metabolismo , Adulto , Artérias , Epinefrina/sangue , Epinefrina/metabolismo , Feminino , Humanos , Masculino , Norepinefrina/sangue , Concentração Osmolar , Período Pós-Prandial , Fatores de TempoRESUMO
The physiological significance of changes in uncoupling protein-2 (UCP-2) gene expression is controversial. In this study we investigated the biochemical and functional correlates of UCP-2 gene expression in sc abdominal adipose tissue in humans in vivo. UCP-2 messenger ribonucleic acid expression was quantified by nuclease protection in adipose tissue from lean and obese humans in both the fasting and postprandial states. Plasma fatty acids, insulin, and leptin were all determined in paired samples from the superficial epigastric vein and radial artery, and local production rates were calculated from 133Xe washout. In the fasting state UCP-2 expression correlated inversely with body mass index (r = -0.45; P = 0.026), percent body fat (r = -0.41; P = 0.05), plasma insulin (r = -0.47; P = 0.02), epigastric venous fatty acids (r = -0.45; P = 0.04), and leptin (r = -0.50; P = 0.018). UCP-2 expression remained inversely related with plasma leptin after controlling for percent body (r = -0.45; P = 0.038). At 2 or 4 h postprandially, there were no significant relationships between UCP-2 expression and biochemical parameters. In conclusion, 1) UCP-2 messenger ribonucleic acid expression in sc adipose tissue is inversely related to adiposity and independently linked to local plasma leptin levels; and 2) UCP-2 expression is not acutely regulated by food intake, insulin, or fatty acids. Reduced UCP-2 expression may be a maladaptive response to sustained energy surplus and could contribute to the pathogenesis and maintenance of obesity.
Assuntos
Tecido Adiposo/fisiologia , Regulação da Expressão Gênica , Proteínas de Membrana Transportadoras , Proteínas Mitocondriais , Proteínas/genética , Tecido Adiposo/irrigação sanguínea , Adulto , Índice de Massa Corporal , Jejum , Ácidos Graxos não Esterificados/sangue , Feminino , Humanos , Insulina/sangue , Canais Iônicos , Leptina/sangue , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/genética , Fluxo Sanguíneo Regional , Transcrição Gênica , Desacopladores , Proteína Desacopladora 2RESUMO
We measured arterio-venous differences in concentrations of tumor necrosis factor-alpha (TNF alpha) and interleukin-6 (IL-6) across a sc adipose tissue bed in the postabsorptive state in 39 subjects [22 women and 17 men; median age, 36 yr (interquartile range, 26-48 yr); body mass index, 31.8 kg/m2 (range, 22.3- 38.7 kg/m2); percent body fat, 28.7% (range, 17.6-50.7%)]. A subgroup of 8 subjects had arteriovenous differences measured across forearm muscle. Thirty subjects were studied from late morning to early evening; 19 ate a high carbohydrate meal around 1300 h, and 11 continued to fast. We found a greater than 2-fold increase in IL-6 concentrations across the adipose tissue bed [arterial, 2.27 pg/mL (range, 1.42-3.53 pg/mL); venous, 6.71 pg/mL (range, 3.36-9.62 pg/mL); P < 0.001], but not across forearm muscle. Arterial plasma concentrations of IL-6 correlated significantly with body mass index (Spearman's r = 0.48; P < 0.01) and percent body fat (Spearman's r = 0.49; P < 0.01). Subcutaneous adipose tissue IL-6 production increased by the early evening (1800-1900 h) in both subjects who had extended their fasting and those who had eaten. Neither deep forearm nor sc adipose tissue consistently released TNF alpha [across adipose tissue: arterial, 1.83 pg/mL (range, 1.36-2.34 pg/mL); venous, 1.85 pg/mL (range, 1.44-2.53 pg/mL); P = NS: across forearm muscle: arterial, 1.22 pg/mL (range, 0.74-2.76 pg/mL); venous, 0.99 pg/mL (range, 0.69-1.70 pg/mL); P = NS]. Although both IL-6 and TNF alpha are expressed by adipose tissue, our results show that there are important differences in their systemic release. TNF alpha is not released by this sc depot. In contrast, IL-6 is released from the depot and is thereby able to signal systemically.
Assuntos
Tecido Adiposo/metabolismo , Interleucina-6/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Abdome/irrigação sanguínea , Adulto , Artérias , Feminino , Antebraço/irrigação sanguínea , Humanos , Interleucina-6/biossíntese , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Concentração Osmolar , Pele , Fator de Necrose Tumoral alfa/análise , Fator de Necrose Tumoral alfa/biossíntese , VeiasRESUMO
The aim of this study was to establish the relation between noninvasive Doppler ultrasound assessments of aortic compliance, based on "foot-to-foot" aortic pulse wave velocity measurements, and presumed atherosclerotic load in patients with vascular disease and/or diabetes mellitus. One hundred ten patients with vascular disease and/or diabetes mellitus (arteriopaths) underwent measurement of in vivo aortic compliance using Doppler ultrasound. Demographic data on these subjects were recorded along with details of cardiovascular risk factors and events. Aortic compliance values were compared with data from 51 age-matched healthy, asymptomatic subjects putatively free of vascular disease (controls). Data are expressed as mean+/-SD. Arteriopaths were aged 64.1+/-8.4 years and had total cholesterol levels of 5.9+/-1.1 mmol/L and aortic compliance of 0.78+/-0.42%/10 mm Hg [1.33 kPa]. Most arteriopaths had 2 or more cardiovascular risk factors and events: diabetes (n=41), hypertension (n=45), smoking (n=86), cerebrovascular/transient ischemic event (n=13), myocardial infarction (n=44), angina (n=51), and/or peripheral vascular disease (n=33). Controls were aged 64.3+/-12.1 years with total cholesterol of 6.1+/-1.1 mmol/L and aortic compliance of 1.14+/-0.46%/10 mm Hg [1.33 kPa] (P<0.002 versus arteriopaths). Subset analysis revealed that patients with the greatest number of cardiovascular risk factors and events (n=5) had the stiffest aortas (aortic compliance, 0.58+/-0.15%/10 mm Hg [1.33 kPa]) compared with those patients with the median and mean (n=2) number of risk factors and events (aortic compliance, 0.80+/-0.50%/10 mm Hg [1.33 kPa]; P<0.02). The data suggest that a significant inverse relation exists between presumed atherosclerotic load (as assessed by the number of cardiovascular risk factors and events) and aortic compliance determined noninvasively based on aortic pulse wave velocity measurements. If these findings are confirmed by prospective, longitudinal follow-up studies, such measurements may prove useful as a noninvasive marker of vascular risk.
Assuntos
Aorta/diagnóstico por imagem , Doenças Cardiovasculares , Diabetes Mellitus/fisiopatologia , Doenças Vasculares/fisiopatologia , Adulto , Idoso , Aorta/fisiopatologia , Pressão Sanguínea , Estudos de Casos e Controles , Colesterol/sangue , Complacência (Medida de Distensibilidade) , Complicações do Diabetes , Diabetes Mellitus/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pulso Arterial , Reprodutibilidade dos Testes , Fatores de Risco , Ultrassonografia Doppler , Doenças Vasculares/complicações , Doenças Vasculares/diagnóstico por imagemRESUMO
Dopamine in the circulation occurs mainly as dopamine sulfate, the sources and physiological significance of which have been obscure. In this study, plasma concentrations of dopamine sulfate were measured after a meal, after fasting for 4 days, and during i.v. L-DOPA, nitroprusside, or trimethaphan infusion in volunteers; after dopamine infusion in patients with L-aromatic-amino-acid decarboxylase deficiency; in arterial and portal venous plasma of gastrointestinal surgery patients; and in patients with sympathetic neurocirculatory failure. Meal ingestion increased plasma dopamine sulfate by more than 50-fold; however, prolonged fasting decreased plasma dopamine sulfate only slightly. L-DOPA infusion produced much larger increments in dopamine sulfate than in dopamine; the other drugs were without effect. Patients with L-aromatic amino acid decarboxylase deficiency had decreased dopamine sulfate levels, and patients with sympathetic neurocirculatory failure had normal levels. Decarboxylase-deficient patients undergoing dopamine infusion had a dopamine sulfate/dopamine ratio about 25 times less than that at baseline in volunteers. Surgery patients had large arterial-portal venous increments in plasma concentrations of dopamine sulfate, so that mesenteric dopamine sulfate production accounted for most of urinary dopamine sulfate excretion, a finding consistent with the localization of the dopamine sulfoconjugating enzyme to gastrointestinal tissues. The results indicate that plasma dopamine sulfate derives mainly from sulfoconjugation of dopamine synthesized from L-DOPA in the gastrointestinal tract. Both dietary and endogenous determinants affect plasma dopamine sulfate. The findings suggest an enzymatic gut-blood barrier for detoxifying exogenous dopamine and delimiting autocrine/paracrine effects of endogenous dopamine generated in a "third catecholamine system."
Assuntos
Dopamina/análogos & derivados , Jejum , Alimentos , Adulto , Descarboxilases de Aminoácido-L-Aromático/deficiência , Artérias , Doenças do Sistema Nervoso Autônomo/sangue , Western Blotting , Dopamina/sangue , Dopaminérgicos , Feminino , Neoplasias Gastrointestinais/sangue , Neoplasias Gastrointestinais/cirurgia , Humanos , Levodopa/administração & dosagem , Levodopa/sangue , Masculino , Nitroprussiato/administração & dosagem , Veia Porta , Trimetafano/administração & dosagemRESUMO
BACKGROUND: Alterations in glucose metabolism during early fasting may be an important trigger of the hormonal and metabolic responses to fasting. OBJECTIVE: The purpose of this study was to determine whether glucose metabolism in response to brief starvation differs in lean and abdominally obese women. DESIGN: We evaluated whole-body glucose metabolism by use of stable-isotope tracer methods and glucose uptake in subcutaneous abdominal adipose tissue by use of arteriovenous balance in 7 lean [58 +/- 2 kg; body mass index (BMI; in kg/m(2)): 21 +/- 5] and 6 abdominally obese (96 +/- 2 kg; BMI: 36 +/- 1) women after 14 and 22 h of fasting. RESULTS: Between 14 and 22 h of fasting, whole-body glucose production and disposal declined in both groups (P < 0.05), but the reduction was 50% greater in lean than in obese women (P < 0.05). The decline in glucose uptake at 22 h of fasting was also lower in obese (0.11 +/- 0.04 micromol*100 g(-1) x min(-1)) than in lean (0.26 +/- 0.03 micromol x 100 g(-1) x min(-1)) women (P < 0.05). Decreases in plasma insulin and leptin concentrations between 14 and 22 h of fasting were also lower in obese than in lean women (insulin: 20 +/- 3% and 32 +/- 5%; leptin: 18 +/- 3% and 37 +/- 6%; both P < 0.05). CONCLUSIONS: The normal decline in glucose production and uptake that occurs during early fasting is blunted in women with abdominal obesity. These alterations in glucose metabolism are associated with a blunted decline in circulating concentrations of both insulin and leptin, which may explain some of the differences in the metabolic response to fasting observed between lean and abdominally obese persons.
Assuntos
Tecido Adiposo/metabolismo , Metabolismo Energético , Jejum/metabolismo , Glucose/metabolismo , Obesidade/metabolismo , Abdome , Tecido Adiposo/anatomia & histologia , Tecido Adiposo/irrigação sanguínea , Adulto , Glicemia/metabolismo , Feminino , Humanos , Insulina/sangue , Cinética , Leptina/sangue , Obesidade/sangue , Fluxo Sanguíneo Regional , Fatores de TempoRESUMO
Arteriovenous differences for lactate and glycerol reported across the human forearm are inconsistent in direction and magnitude. Such inconsistency could represent the effects of differing forearm compositions. The hypothesis was tested by examination of 37 studies of forearm arteriovenous differences for lactate, glycerol, glucose, and oxygen (only measured in 25 studies) in 23 normal subjects after overnight fast. In 16 studies, glycerol was taken up rather than released by the forearm, and in 12 of these the arteriovenous difference was greater than could be accounted for by analytical variation. The arteriovenous differences for glycerol and lactate were positively correlated (r = .44, P less than .01). The hypothesis that glycerol and lactate uptake might reflect a more "oxidative" forearm was not borne out, since neither glycerol nor lactate arteriovenous differences correlated with that for oxygen, although oxygen and glucose arteriovenous differences and fluxes were correlated (fluxes: r = .60, P less than .01). The arteriovenous difference for glycerol was positively related to body mass index, arguing against a variable contribution from fat. The hypothesis that the direction of glycerol and lactate exchange would reflect the forearm composition was not borne out by the analysis of repeated studies on the same individual, which showed that the variation within subjects was not significantly less than that between subjects. Therefore, we conclude that in approximately 40% of studies in normal subjects after an overnight fast, the forearm will show glycerol uptake, although we have been unable to identify any physiological reason for this phenomenon. Peripheral glycerol uptake has implications for studies in which glycerol release is taken as a measure of lipolysis.
Assuntos
Antebraço/irrigação sanguínea , Glicerol/sangue , Lactatos/sangue , Adulto , Análise de Variância , Artérias , Glicemia/análise , Feminino , Humanos , Ácido Láctico , Masculino , Pessoa de Meia-Idade , Oxigênio/sangue , VeiasRESUMO
We have examined the regulation of lipid and glucose metabolism in the postabsorptive and postprandial states in six subjects with insulin-treated diabetes mellitus, and compared them with eight nondiabetic subjects. Blood or plasma concentrations of metabolites and fluxes across forearm and subcutaneous adipose tissue were studied after an overnight fast and for 6 hours after a mixed meal (3.1 MJ, 41% from fat). In the postabsorptive state, regulation of lipid metabolism in the two groups appeared basically similar except that a wider spread of plasma (free) insulin concentrations in the diabetic group led to a wider range of values of plasma nonesterified fatty acid (NEFA) release from adipose tissue, plasma NEFA concentrations, and blood ketone body concentrations. Extraction of ketone bodies across adipose tissue was positively correlated with arterial concentration in both groups (as it was in the forearm), confirming the ability of human adipose tissue to utilize ketone bodies. A single subcutaneous injection of insulin before the meal in the diabetic group produced a plasma free-insulin profile that was blunted and prolonged compared with the postprandial response in the control group. Postprandial forearm glucose uptake followed very closely the plasma (free) insulin concentration. Postprandial suppression of NEFA release from adipose tissue was essentially normal in the diabetic group, and the normal postprandial decrease in plasma NEFA concentrations was reproduced extremely closely. Forearm and adipose tissue blood flow did not differ between the groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Diabetes Mellitus Tipo 1/metabolismo , Alimentos , Insulina/uso terapêutico , Metabolismo dos Lipídeos , Tecido Adiposo/metabolismo , Adulto , Glicemia/metabolismo , Peptídeo C/sangue , Diabetes Mellitus Tipo 1/tratamento farmacológico , Jejum , Ácidos Graxos não Esterificados/sangue , Ácidos Graxos não Esterificados/metabolismo , Feminino , Humanos , Insulina/sangue , Corpos Cetônicos/metabolismo , Lipídeos/sangue , Masculino , Pessoa de Meia-IdadeRESUMO
The objective of this study was to demonstrate directly, by measurement of arteriovenous concentration differences, the interconversion of steroid hormones in human subcutaneous adipose tissue in vivo. Simultaneous arterial (or arterialized) and adipose tissue-venous plasma samples were collected from eight men and seven women, for measurement of estradiol, estrone, testosterone, and androstenedione concentrations by radioimmunoassay. Despite the heterogeneity of the groups (premenopausal and postmenopausal women, one subject with insulin-dependent diabetes mellitus), some very consistent findings emerged. Both estrogens were added to plasma during passage through adipose tissue in almost all subjects (P less than .01 for each hormone). In all the men but one, testosterone was removed from plasma, and the arteriovenous difference was correlated with the arterial concentration (r = .70, P = .05). In all the women but one (in whom there was no change), the testosterone concentration increased during passage through adipose tissue. The handling of androstenedione was less consistent. This study demonstrates the feasibility of direct measurement of the peripheral production or utilization of steroid hormones, and confirms the belief that adipose tissue is an important site for such interconversions.
Assuntos
Tecido Adiposo/metabolismo , Hormônios Esteroides Gonadais/metabolismo , Tecido Adiposo/irrigação sanguínea , Adulto , Idoso , Artérias , Feminino , Hormônios Esteroides Gonadais/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Concentração Osmolar , VeiasRESUMO
Measurements of arteriovenous differences across subcutaneous abdominal tissue (mainly adipose) and deep forearm tissue (mainly muscle) were made on 25 occasions in normal subjects after an overnight fast. Adipose tissue was shown to be strongly lipolytic (releasing nonesterified fatty acids and glycerol), to clear circulating triacylglycerol, glucose, ketone bodies and acetate, and to produce lactate. Uptake of circulating carbohydrate and ketones was sufficient to account for only 51% of the adipose tissue oxygen consumption, implying that adipose tissue utilizes fuel(s) stored within it. The mean fractional re-esterification rate of fatty acids in adipose tissue was 13% to 19%. Arteriovenous differences were converted to fluxes of carbon atoms to compare the movements of different fuels. (Amino acids were not included in these calculations.) Adipose tissue after an overnight fast was a net exporter of carbon, whereas in resting muscle the uptake of carbon atoms from circulating carbohydrate and lipid fuels approximately balanced the CO2 production. Fatty acids were the main form in which carbon left adipose tissue, and the main source of carbon atoms entering the resting forearm.
Assuntos
Tecido Adiposo/irrigação sanguínea , Glicemia/análise , Carboidratos/sangue , Jejum , Lipídeos/sangue , Músculos/irrigação sanguínea , Acetatos/sangue , Adulto , Artérias , Dióxido de Carbono/sangue , Feminino , Antebraço/irrigação sanguínea , Glicerol/sangue , Humanos , Corpos Cetônicos/sangue , Lactatos/sangue , Lipólise , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Oxigênio/sangue , Piruvatos/sangue , Triglicerídeos/sangue , VeiasRESUMO
Lipoprotein lipase (LPL) plays a pivotal role in very-low-density lipoprotein (VLDL) metabolism. Within the circulation, the VLDL population is heterogeneous with respect to both size and composition. Several studies have investigated the action of LPL in vitro on different VLDL subfractions, but little is known of the action of LPL in vivo. To investigate this, arterial and adipose tissue venous plasma samples were obtained from 16 normal male healthy volunteers (aged 24.4 +/- 1.8 years; body mass index, 23.5 +/- 0.7 kg.m-2) following an overnight fast. VLDL subfractions were isolated (VLDL1 of Sf 60 to 400 and VLDL2 of Sf 20 to 60) and characterized in terms of triacylglycarol (TAG) and apolipoprotein (apo) B, E, CI, CII, and CIII content. The apolipoprotein content of VLDL1 differed from that of VLDL2: the VLDL2 fraction contained significantly more apo B (0.018 +/- 0.004 v 0.011 +/- 0.003 mumol.L-1, p = .001) but the ratios of TAG:apo B and apo CI:B, and CII:B, and CIII:B were significantly higher in VLDL1 (48,200 +/- 7,980 v 13,860 +/- 2,420, 22.7 +/- 5.5 v 12.5 +/- 2.2, 45.0 +/- 6.3 v 14.9 +/- 2.0, and 0.434 +/- 0.077 v 0.357 +/- 0.054, respectively, molar ratios, all P < .05). The venous blood draining an adipose tissue depot contained less VLDL1-TAG than arterial blood (328 +/- 68 v 381 +/- 83 mumol.L-1, respectively, P < .01), whereas VLDL2-TAG exhibited an opposite tendency (199 +/- 46 v 172 +/- 31 mumol.L-1, NS). Concentrations of VLDL1-apo B, -apo CII, and -apo CIII were significantly less in adipose tissue venous blood compared with arterial blood (0.011 +/- 0.004 v 0.013 +/- 0.004, 0.38 +/- 0.08 v 0.43 +/- 0.10, and 1.33 +/- 0.35 v 1.58 +/- 0.38 mumol.L-1, respectively, all P < .05). These studies demonstrated novel differences in VLDL1 and VLDL2 in terms of composition and metabolism by human adipose tissue LPL in vivo.
Assuntos
Tecido Adiposo/metabolismo , Lipase Lipoproteica/metabolismo , Lipoproteínas VLDL/metabolismo , Adulto , Apolipoproteínas/análise , Apolipoproteínas/metabolismo , Artérias , Humanos , Lipoproteínas VLDL/sangue , Lipoproteínas VLDL/isolamento & purificação , Masculino , Triglicerídeos/análise , Triglicerídeos/metabolismo , VeiasRESUMO
Although excess ethanol consumption is often considered to lead to adiposity, the metabolic routes by which this might occur are not clear. We have investigated some metabolic consequences of acute ethanol ingestion by measuring arteriovenous differences across forearm muscle and subcutaneous adipose tissue for 6 hours after ingestion of 47.5 g ethanol, in seven normal subjects fasted overnight. The expected systemic effects of ethanol ingestion were observed: slight lowering of the plasma glucose concentration, depression of plasma nonesterified fatty acid (NEFA) concentrations, and elevation of the blood lactate/pyruvate and 3-hydroxybutyrate/acetoacetate ratios. There was a marked reduction in blood total ketone bodies in relation to plasma NEFA concentrations. However, the only major change observed in peripheral tissue metabolism was an increased uptake of acetate into forearm muscle, equivalent, in whole-body terms, to only 3% of the ethanol load. Adipose tissue appeared to show a reduced cytoplasmic state in that it exported an increased ratio of lactate to pyruvate after ethanol ingestion. However, this reduced state did not lead to increased fatty acid reesterification within adipose tissue. No mechanism was clearly identified whereby ethanol ingestion might lead to net deposition of triacylglycerol in adipose tissue.