棕色脂肪形成的研究进展

棕色脂肪组织在小型哺乳动物和新生儿中较丰富,有助于抵御寒冷。很久以来认为成年人缺乏棕色脂肪组织或甚至不存在也无关紧要。然而,最近的研究显示成人也存在有代谢活性的棕色脂肪组织,并在能量平衡中发挥重要作用。从临床的角度看,棕色脂肪组织是治疗肥胖及相关的代谢性疾病的潜在靶标。     

Fat metabolism in brown adipose tissue in vivo

1. Noradrenaline infusions (I.V. for 30 min) in new-born and 1-week-old unanaesthetized rabbits caused a rapid and sustained rise in oxygen consumption and an increase in blood glucose, free fatty acid and glycerol concentrations. Similar changes occurred in anaesthetized 1-week-old rabbits.2. A simple direct method was used to measure the net exchange of metabolites across brown adipose tissue in anaesthetized young rabbits. It was found that the brown adipose tissue of rabbits reared from birth in a thermoneutral environment and studied when their next feed was due took glucose from and released fatty acids and glycerol into the circulation.3. Similar rabbits kept unfed for a further 48 hr in a warm environment released fatty acids and glycerol from their brown adipose tissue at a far greater rate, but the rate of glucose uptake was reduced.4. On the other hand the brown adipose tissue of rabbits kept unfed in a cold environment (20 degrees C) took up circulating free fatty acids as well as glucose and did not release glycerol. The brown adipose tissue of these rabbits was depleted of fat.5. The rate of blood flow through brown adipose tissue and the exchange of all three metabolites increased fourfold during noradrenaline infusion in the three groups of rabbits.6. It is concluded (i) that brown adipose tissue releases significant amounts of fatty acids and glycerol into the circulation and that this contribution is greatly increased with noradrenaline infusion and presumably cold exposure, and (ii) that brown adipose tissue depleted of fat produces heat by drawing free fatty acids as well as glucose from the circulation.     

Noradrenaline-induced changes in rat brown adipose tissue glucagon

Brown adipose tissue (BAT) glucagon level was higher in cold-acclimated rats (CA) than in warm controls (WC). Noradrenaline (NA) injection increased BAT glucagon levels in both WC and CA with increases in plasma glucagon levels. The magnitude of increase was significantly greater in CA for plasma glucagon, while it did not differ for BAT between groups. However, BAT glucagon was kept at a higher level in CA after NA injection than in WC.     

Cold-induced changes in glucagon of brown adipose tissue

In order to evaluate the role of glucagon in brown adipose tissue (BAT) function under cold or stress, the changes in immunoreactive glucagon of BAT and plasma as well as uptake and metabolism of radioactive glucagon (125I-G) in this tissue were studied in rats. Glucagon per g fresh tissue was higher in the dorso-cervical BAT than in the interscapular BAT. In warm controls (WC), acute cold exposure (-5 degrees C, 15 min) (CE) or stress (immobilization, 30 min) (AS) elevated glucagon of both sites of BAT as well as plasma. In cold-acclimated animals (CA), the resting levels of BAT glucagon, but not plasma glucagon, were higher than WC. CE caused elevation of plasma glucagon, but not BAT glucagon in CA. AS did not affect glucagon levels in both plasma and BAT in CA. Cold acclimation did not influence 125I-G uptake by BAT, but resulted in a rather lower 125I-G level in plasma and liver. The present results suggest that BAT is a target tissue for glucagon to cause nonshivering thermogenesis in response to cold or stress and that turnover of glucagon is enhanced by cold acclimation.     

Catecholaminergic and peptidergic nerves in naturally occurring and pheochromocytoma-associated human brown adipose tissue

Noradrenergic and peptidergic innervations in naturally occurring and pheochromocytoma-associated human perirenal brown adipose tissue were demonstrated. The presence of both parenchymal and periarterial noradrenergic nerve plexuses was revealed by the sucrose-potassium-glyoxylic-acid (SPG) technique in all tissue samples. Immunohistochemical studies also indicated the presence of neuropeptide Y-like, calcitonin gene-related peptidelike, substance P-like, and bombesinlike immunoreactive nerves in the adventitia of both inter- and intralobular arteries. At a more peripheral level, only neuropeptide Y-like immunoreactive elements were observed in the parenchymal field. No somatostatinlike or enkephalinlike immunoreactivity was detected. The specific distributions of noradrenergic and peptidergic nerves were similar in both naturally occurring and pheochromocytoma-associated brown adipose tissue. Thus these findings indicate a plurality of innervation in human perirenal brown fat.     

Differential responses of white adipose tissue and brown adipose tissue to caloric restriction in rats

Caloric restriction (CR) slows the aging process and extends longevity, but the exact underlying mechanisms remain debatable. It has recently been suggested that the beneficial action of CR may be mediated in part by adipose tissue remodeling. Mammals have two types of adipose tissue: white adipose tissue (WAT) and brown adipose tissue (BAT). In this study, proteome analysis using two-dimensional gel electrophoresis combined with MALDI-TOF MS, and subsequent analyses were performed on both WAT and BAT from 9-month-old male rats fed ad libitum or subjected to CR for 6 months. Our findings suggest that CR activates mitochondrial energy metabolism and fatty acid biosynthesis in WAT. It is likely that in CR animals WAT functions as an energy transducer from glucose to energy-dense lipid. In contrast, in BAT CR either had no effect on, or down-regulated, the mitochondrial electron transport chain, but enhanced fatty acid biosynthesis. This suggests that in CR animals BAT may change its function from an energy consuming system to an energy reservoir system. Based on our findings, we conclude that WAT and BAT cooperate to use energy effectively via a differential response of mitochondrial function to CR.     

The occurrence of brown adipose tissue in outdoor workers

Summary Histochemical reactions and activities of mitochondrial enzymes in adipose tissue around the neck arteries and in pericardium were studied in men who had been outdoor workers in northern Finland. The purpose was to study the occurrence of brown fat in workers having been exposed to cool or cold ambient temperature. Indoor workers of the same age were used as controls.Histochemically, no mitochondrial enzyme reactions were seen in the adipose tissues taken from the indoor workers, whereas some outdoor workers had some multilocular adipose tissue, mostly around the neck arteries. Biochemical parameters also showed increased enzyme activities of aerobic energy metabolism in the adipose tissue of these people.The present results suggest that working in the cold can retain brown adipose tissue in strategic places in human adults.     

Long-term alcohol consumption and brown adipose tissue in man

Summary The purpose of the present work was to study whether long-term alcohol consumption in man affects the develeopment of brown adipose tissue. The adipose tissue around the thoracic aorta and common carotid arteries was collected at medicolegal autopsies on adults with a positive record of heavy alcohol consumption. Adults without any evident history of alcohol consumption served as controls. Histochemical reactions of the oxidative mitochondrial enzymes, cytochrome oxidase and succinate dehydrogenase were studied in samples of this adipose tissue and the activities of the enzymes were measured biochemically.There was histological evidence of some multilocular adipose tissue around the thoracic aorta and common carotid arteries of the alcohol consumers, whereas the adipose tissue from the non-drinkers was mostly unilocular resembling white adipose tissue. Histochemical evidence of brown adipose tissue was found in all alcohol consumers, but also in some of the controls. Biochemical cytochrome oxidase (CYO) and succinate dehydrogenase measurements in isolated mitochondria showed activity in 70% of the cases of drinkers and in one of the eight controls. Activity of CYO was measurable in the mitochondria from two other controls. The protein content of the samples from the alcoholics was twice that of the controls. The results suggest that chronic alcohol intake may induce a change in the white adipose tissue around the thoracic aorta and common carotid arteries of human adults into brown fat.     

Interscapular brown adipose tissue blood flow in the rat

The xenon clearance method was adapted to continuous measurement of interscapular brown adipose tissue (ISBAT) blood flow in anaesthetized rats.The ISBAT-blood partition coefficient for xenon was determined to 3.6 ml·g^–1. The blood flow values obtained by Xe clearance were compared with flow values obtained concomitantly by the microsphere technique in 17 cold acclimated rats, at ISBAT blood flows between 0.1 and 6 ml·g^–1·min^–1. Variations in blood flows were obtained by infusion of noradrenaline at different rates.The blood flow values obtained from the xenon clearance method showed a close correlation to the blood flow values determined with microspheres.Y=0.98.X+0.15 (r=0.96,P<0.001).The Xe clearance method has the advantages compared to the microsphere technique that it permits continuous monitoring of the blood flow and does not require the sacrifice of the animal.     

Intra- and interindividual variation in gene expression in human adipose tissue

Adipose tissue is a highly plastic tissue with an important endocrine and metabolic function. To understand its role in human health and disease, it is necessary to understand the extent of variation and the specific differences within and between different depots and subjects. We employed cDNA microarray analysis to investigate this in human subjects ranging from lean to mildly obese. We observe (1) high similarity between different samples of one adipose depot, (2) only small differences between the subcutaneous and visceral adipose tissue depot and (3) larger differences in gene expression between different individuals (per depot). The major variation within adipose depots can be attributed to differences in the non-adipocyte component of adipose tissue. Using only non-obese subjects, we identified genes that were consistently differentially expressed between subcutaneous and omental adipose tissue, despite the variation in gene expression between these subjects. Using quantitative real time polymerase chain reaction (PCR), fatty acid binding protein 4 (FABP4), vimentin (Vim), four and a half LIMs domains (FHL1), CD36 (all higher in subcutaneous adipose tissue) and Matrix Gla protein (MGP; lower in subcutaneous adipose tissue) were confirmed to be significantly differentially expressed between depots.