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1.
The innervation of rat interscapular brown adipose tissue has been studied by light and fluorescence microscopy and electron microscopy after treatment with "false" adrenergic neurotransmitters 5- and 6-hydroxydopamine. The vascular markers neoprene latex and thioflavin S were used to define the blood vascular arrangements within the around the tissue. Catecholaminergic innervation was revealed by fluorescence microscopy at both parenchymal and vasomotor sites. In animals injected with 6-hydroxydopamine, this catecholaminergic fluorescence was extinguished in the parenchymal nerve distribution and markedly reduced in the vasomotor plexus. Identification of an extensive network of noradrenergic vasomotor and parenchymal nerve terminals was established by electron microscopy after 5- and 6-hydroxydopamine administration, but unmarked terminals were also observed in both distributions. These unmarked terminals might represent an additional nonnoradrenergic nerve supply to interscapular brown adipose tissue. The thoracodorsal veins draining the fat pads are directly tributary to a large median perforating vein, which joins the azygos vein, and are also continuous with the axillary vein. In addition to the recognized vascular distribution pattern of lobular arteries supplying an abundant capillary plexus drained by lobular veins, direct arteriovenous anastomoses were observed within the interscapular brown fat pad. It is postulated that these additional vascular arrangements are determinant in the phenomenal increase in blood flow through brown adipose tissue during metabolic stimulation.  相似文献   

2.
The relationship between brown adipose tissue (BAT) and its sympathetic innervation during development was investigated by transplantation of undifferentiated (white fat-like) hamster BAT into the anterior eye chamber of adult hamsters. Such transplants are known to be revascularized and reinnervated by the vessels and the nerves of the host iris. The morphology of the BAT transplants was analysed during the post-operative weeks by light and electron microscopy, and the ingrowth of sympathetic nerve fibres from the iris was followed by radioautography. BAT appeared to differentiate in oculo, i.e. presented increasing amounts of adipocytes with multilocular fat deposits and abundant, well-developed mitochondria, but only after a delay of approx. 10 days, and remained much fatter than in situ. The establishment of the sympathetic innervation was not synchronous with the revascularization process. It occurred simultaneously with the morphological differentiation of the BAT transplants, and the nerve fibre density remained low. In the absence of sympathetic innervation, i.e. when the host irides were sympathectomized prior to transplantation, BAT still differentiated, but the process was further delayed and the proportion of differentiated brown adipocytes after 20 days in oculo was clearly lower than in control transplants. It is concluded that the sympathetic innervation in BAT is involved in the regulation of differentiating activity in the tissue, but is not obligatory for differentiation to occur.  相似文献   

3.
Heat production in brown adipose tissue (BAT) and brown adipocyte recruitment depend heavily on BAT vascular and parenchymal sympathetic and sensory innervation. The expression and distribution of Sema3a, a recently discovered chemorepellent neuronal factor active on both sympathetic and sensory peripheral nerves, were studied in interscapular rat BAT. In rats maintained in thermoneutral conditions, brown adipocytes produced both active isoforms of Sema3a and showed a distinct peripheral polarized immunostaining pattern. This suggests a role for Sema3a secreted by brown adipocytes in the guidance of axons toward their correct targets. In cold-acclimated rats, where parenchymal nerve density is higher, both the expression and the immunostaining of the two active isoforms were slightly but significantly reduced and the distinct staining pattern was not observed. These data suggest that the secretion of Sema3a is inhibited in the brown adipocytes of cold-acclimated rats. Thus, Sema3a could play a role in the plastic adjustment of BAT innervation observed in different conditions of functional demand.  相似文献   

4.
Liver tissue from 12 different mammalian species was studied with a fluorescence histochemical technique for the cellular localization of amines (Falck-Hillarp technique) and with a chemical method for the determination of norepinephrine (HPLC-technique). Adrenergic nerve plexus were found in interlobular blood vessels derived from the portal vein and hepatic artery. Varicose adrenergic nerve fibres were, generally, seen to branch from the fibres around the blood vessels and to enter the liver parenchyma, where they formed a randomly distributed intralobular network. The density of these intralobular fibres showed marked species variation. Human liver and liver from the rhesus monkey, baboon, cynomolgus monkey and guinea pig showed a high density of parenchymal adrenergic nerves. Rabbit, cat, pig, cow and horse liver formed an intermediate group, having fewer varicose adrenergic nerve fibres but an unequivocal distribution of these nerves to the liver parenchyma. In rat and mouse liver no parenchymal innervation could be demonstrated. The density of the parenchymal innervation generally correlated with the concentration of norepinephrine in the liver tissue.  相似文献   

5.
Histochemistry and electron microscopy were used to study the adrenergic innervation of subcutaneous adipose tissue in fetal pigs. Adrenergic innervation was present around arteries, arterioles, and adipocyte-associated capillaries. Nerve fibers were infrequently observed around veins, venules, and adipocytes. Ultrastructural features of nerves included mitochondria, clear synaptic vesicles, and a small number of vesicles with a core of electron-dense material. Innervation of adipose tissue was similar in 70-, 90-, and 110-day-old fetuses. Examination of fetuses decapitated at 45 days of gestation and removed at 110 days showed that adrenergic innervation was absent in adipose tissue of decapitated fetuses. Adrenergic innervation was also absent in adipose tissue from fetuses hypophysectomized at 72-73 days of gestation and examined at 110 days. These data indicate that fetal porcine adipose tissue may be under neural control by day 70 of gestation. Furthermore, an intact pituitary is necessary for the development of adrenergic innervation in fetal adipose tissue.  相似文献   

6.
In the mammalian adipose organ cold exposure not only activates typical brown adipose tissue, but also induces browning, that is the formation of thermogenic multilocular adipocytes in white, or predominantly white, adipose depots such as subcutaneous fat. Unlike typical brown adipocytes, newly formed thermogenic adipocytes have been reported not to express the gene zinc finger of the cerebellum 1 (Zic1). Here, a time course approach enabled us to document a significant increase in Zic1 messenger RNA in inguinal subcutaneous fat from acutely (24 hr) cold-exposed mice, which was paralleled by an increase in multilocular and paucilocular uncoupling protein 1-positive adipocytes and in parenchymal noradrenergic innervation. This transient, depot-specific molecular signature was associated not to Zic1 promoter demethylation, but to chromatin remodeling through an H3K9me3 histone modification. These findings challenge the notion that Zic1 is exclusively expressed by typical brown adipocytes and suggest its involvement in brown adipocyte precursor differentiation and/or white-to-brown adipocyte transdifferentiation.  相似文献   

7.
The adrenergic innervation of structures in the gills of brown and rainbow trout was studied with catecholamine fluorescence histochemistry. In the arterio-arterial vascular pathway, there was an innervation of the afferent and efferent lamellar arterioles, but the afferent and efferent filamental arteries and the secondary lamellae were devoid of any fluorescent nerve fibres. In S. trutta only, there was an additional innervation of the afferent and efferent branchial arteries and the base of the efferent filamental artery. The innervation of the arterio-venous vascular pathway was similar in both trout species. Many fluorescent nerve fibres were found on nutritive arterioles in the gill arch and interbranchial septum, and in the core of each filament between the surface epithelium and the wall of the filament venous sinus. No fluorescent nerve fibres were observed at the origins of the capillaries arising from the efferent filamental artery. The sympathetic nerve supply is provided to the gills mainly through the posttrematic nerve, with an occasional small contribution through the pretrematic nerve. The presence of adrenergic nerves in the gills is discussed in relation to the regulation of blood flow through the arterio-arterial and arterio-venous pathways.  相似文献   

8.
An autoimmune model for in utero immunosympathectomy of fetal rabbits was developed. Non-pregnant, female rabbits were injected with purified nerve growth factor and then bred after confirmation of high titers of anti-nerve growth factor antiserum. Fetuses were delivered and sacrificed at 27 and 31 days gestation and tissue norepinephrine concentration was used as an index of sympathetic innervation. There were significant reductions in tissue norepinephrine at both gestational ages. At 31 days there was a 32% reduction in lung norepinephrine concentration, 46% in the heart and 60% in brown adipose tissue. Corresponding reductions at 27 days were 68% for lung, 44% for heart and 49% for brown adipose tissue. Adrenal catecholamine content was unaffected but para-aortic gland catecholamines were slightly increased. Pulmonary beta adrenergic receptors showed a 30% up regulation in response to dennervation. Carcass weight was reduced 15% to 11% in the dennervated animals. These results demonstrate that dependence of organ sympathetic innervation on nerve growth factor can be demonstrated as early as 27 days gestation. This is a useful model to study the timing and dependence of organ sympathetic innervation on nerve growth factor and the factors which regulate this dependence.  相似文献   

9.
Tyrosine hydroxylase (TH) mRNA and activity and concentrations of 3,4-dihydroxyphenylalanine (DOPA) and catecholamines were examined as markers of sympathetic innervation and catecholamine synthesis in peripheral tissues of sympathectomized and intact rats. Chemical sympathectomy with 6-hydroxydopamine (6-OHDA) markedly decreased norepinephrine and to a generally lesser extent TH activities and dopamine in most peripheral tissues (stomach, lung, testis, duodenum, pancreas, salivary gland, spleen, heart, kidney, thymus). Superior cervical ganglia, adrenals and descending aorta were unaffected and vas deferens showed a large 92% decrease in norepinephrine, but only a small 38% decrease in TH activity after 6-OHDA. Presence of chromaffin cells or neuronal cell bodies in these latter tissues, indicated by consistent expression of TH mRNA, explained the relative resistance of these tissues to 6-OHDA. Stomach also showed consistent expression of TH mRNA before, but not after 6-OHDA, suggesting that catecholamine synthesizing cells in gastric tissue are sensitive to the toxic effects of 6-OHDA. Tissue concentrations of DOPA were mainly unaffected by 6-OHDA, indicating that much of the DOPA in peripheral tissues is synthesized independently of local TH or sympathetic innervation. The differential effects of chemical sympathectomy on tissue catecholamines, DOPA, TH mRNA and TH activity demonstrate that these variables are not simple markers of sympathetic innervation or catecholamine synthesis. Other factors, including presence of neuronal cell bodies, parenchymal chromaffin cells, non-neuronal sites of catecholamine synthesis and alternative sources of tissue DOPA, must also be considered when tissue catecholamines, DOPA and TH are examined as markers of sympathetic innervation and local catecholamine synthesis.  相似文献   

10.
Chronic adrenergic activation leads to the emergence of beige adipocytes in some depots of white adipose tissue in mice. Despite their morphological similarities to brown adipocytes and their expression of uncoupling protein 1 (UCP1), a thermogenic protein exclusively expressed in brown adipocytes, the beige adipocytes have a gene expression pattern distinct from that of brown adipocytes. However, it is unclear whether the thermogenic function of beige adipocytes is different from that of classical brown adipocytes existing in brown adipose tissue. To examine the thermogenic ability of UCP1 expressed in beige and brown adipocytes, the adipocytes were isolated from the fat depots of C57BL/6J mice housed at 24°C (control group) or 10°C (cold-acclimated group) for 3 weeks. Morphological and gene expression analyses revealed that the adipocytes isolated from brown adipose tissue of both the control and cold-acclimated groups consisted mainly of brown adipocytes. These brown adipocytes contained large amounts of UCP1 and increased their oxygen consumption when stimulated with norepinephirine. Adipocytes isolated from the perigonadal white adipose tissues of both groups and the inguinal white adipose tissue of the control group were white adipocytes that showed no increase in oxygen consumption after norepinephrine stimulation. Adipocytes isolated from the inguinal white adipose tissue of the cold-acclimated group were a mixture of white and beige adipocytes, which expressed UCP1 and increased their oxygen consumption in response to norepinephrine. The UCP1 content and thermogenic ability of beige adipocytes estimated on the basis of their abundance in the cell mixture were similar to those of brown adipocytes. These results revealed that the inducible beige adipocytes have potent thermogenic ability comparable to classical brown adipocytes.  相似文献   

11.
Catecholamines are an important regulator of lipolysis in adipose tissue. Here we show that rat adipocytes, isolated from mesenteric adipose tissue, express genes of catecholamine biosynthetic enzymes and produce catecholamines de novo. Administration of tyrosine hydroxylase inhibitor, alpha-methyl-p-tyrosine, in vitro significantly reduced concentration of catecholamines in isolated adipocytes. We hypothesize that the sympathetic innervation of adipose tissues is not the only source of catecholamines, since adipocytes also have the capacity to produce both norepinephrine and epinephrine.  相似文献   

12.
Brown adipose tissue (BAT), a major site for mammalian non‐shivering thermogenesis, could be a target for prevention and treatment of human obesity. Transient receptor potential vanilloid 2 (TRPV2), a Ca2+‐permeable non‐selective cation channel, plays vital roles in the regulation of various cellular functions. Here, we show that TRPV2 is expressed in brown adipocytes and that mRNA levels of thermogenic genes are reduced in both cultured brown adipocytes and BAT from TRPV2 knockout (TRPV2KO) mice. The induction of thermogenic genes in response to β‐adrenergic receptor stimulation is also decreased in TRPV2KO brown adipocytes and suppressed by reduced intracellular Ca2+ concentrations in wild‐type brown adipocytes. In addition, TRPV2KO mice have more white adipose tissue and larger brown adipocytes and show cold intolerance, and lower BAT temperature increases in response to β‐adrenergic receptor stimulation. Furthermore, TRPV2KO mice have increased body weight and fat upon high‐fat‐diet treatment. Based on these findings, we conclude that TRPV2 has a role in BAT thermogenesis and could be a target for human obesity therapy.  相似文献   

13.
Thermogenesis in brown adipocytes, conferred by mitochondrial uncoupling protein 1 (UCP1), is receiving great attention because metabolically active brown adipose tissue may protect humans from metabolic diseases. In particular, the thermogenic function of brown‐like adipocytes in white adipose tissue, known as brite (or beige) adipocytes, is currently of prime interest. A valid procedure to quantify the specific contribution of UCP1 to thermogenesis is thus of vital importance. Adrenergic stimulation of lipolysis is a common way to activate UCP1. We here report, however, that in this frequently applied setup, taking control over intracellular fatty acid levels is essential for the analysis of thermogenic function in cultured brown and brite adipocytes. By the application of these findings, we demonstrate that UCP1 is functionally thermogenic in intact brite adipocytes and adrenergic UCP1 activation is largely dependent on adipose triglyceride lipase (ATGL) rather than hormone sensitive lipase (HSL).  相似文献   

14.
The adipose organ   总被引:1,自引:0,他引:1  
In mammals, the adipose tissues are contained in a multi-depot organ: the adipose organ. It consists of several subcutaneous and visceral depots. Some areas of these depots are brown and correspond to brown adipose tissue, while many are white and correspond to white adipose tissue. The organ is rich of vessels and parenchymal nerve fibers, but their density is higher in the brown areas. White areas contain a variable amount of brown adipocytes and their number varies with age, strain and environmental conditions. All adipocytes of the adipose organ express a specific adrenoceptor: ss3AR. Recent data have stressed the plasticity of the adipose organ in adult animals, and in parallel with the cytological variations there are also vascular as well as neural variations. Of note, treatment of genetically and diet induced obese rats with ss3 adrenoceptor agonists ameliorate their pathological condition and this is accompanied by the appearance of brown adipocytes in white areas of the adipose organ. This drug-induced modification of the anatomy of the organ is also obtained by the treatment with PPARgamma agonists in rats and dogs. We have previously shown that the transformation of white adipose tissue into brown adipose tissue in rats treated with ss3 adrenoceptor agonists is due to a direct transformation of differentiated unilocular adipocytes (transdifferentiation). We recently also showed that the absence of ss3 adrenoceptors strongly depress this type of plasticity in the adipose organ. All together these experiments strongly suggest the possibility to modulate the plasticity of the adipose organ with therapeutic implications for obesity and related disorders.  相似文献   

15.
Stimulation of brown adipocytes by their sympathetic innervation plays a major role in body energy homeostasis by regulating the energy- wasting activity of the tissue. The norepinephrine released by sympathetic activity acts on adrenergic receptors to activate a variety of metabolic and membrane responses. Since sympathetic stimulation may also release vesicular ATP, we tested brown fat cells for ATP responses. We find that micromolar concentrations of extracellular ATP initiates profound changes in the membrane trafficking of brown adipocytes. ATP elicited substantial increases in total cell membrane capacitance, averaging approximately 30% over basal levels and occurring on a time scale of seconds to minutes. The membrane capacitance increase showed an agonist sensitivity of 2-methylthio-ATP > or = ATP > ADP > > adenosine, consistent with mediation by a P2r type purinergic receptor. Membrane capacitance increases were not seen when cytosolic calcium was increased by adrenergic stimulation, and capacitance responses to ATP were similar in the presence and absence of extracellular calcium. These results indicate that increases in cytosolic calcium alone do not mediate the membrane response to ATP. Photometric assessment of surface-accessible membrane using the dye FM1- 43 showed that ATP caused an approximate doubling of the amount of membrane actively trafficking with the cell surface. The discrepancy in the magnitudes of the capacitance and fluorescence changes suggests that ATP both activates exocytosis and alters other aspects of membrane handling. These findings suggest that secretion, mobilization of membrane transporters, and/or surface membrane expression of receptors may be regulated in brown adipocytes by P2r purinergic receptor activity.  相似文献   

16.
  • 1.1. Fluorescence and electron microscopy were used to visualize differences between avian adipose tissue (AAT) collected from clavicular and abdominal regions of the great tit, the willow tit, the house sparrow and the Japanese quail, and interscapular brown adipose tissue (BAT) obtained from the Djungarian dwarf hamster.
  • 2.2. Multilocular fat cells were found in AAT. The prerequisite for multilocularity, however, was not simply winter acclimatization [short photophase 4L:20D and low ambient temperature (< −20°C in January in Oulu)] or cold-acclimation (−25°C). Multilocular adipocytes were found during autumn and in unacclimated control birds as well. Mitochondria in the AAT were fewer and about one-sixth the length of those in BAT. This finding was associated with low cytochrome oxidase (COX) activity in the tissue homogenate and isolated mitochondrial fraction of the AAT (< 5.2% of that in BAT).
  • 3.3. Catecholamine fluorescence was seen only around arteries in the AAT. Signs of sympathetic parenchymal innervation were found neither in winter- nor in cold-acclimated birds, but typically, sympathetic nerve fibers forming a basket-like network around every cell were seen in the brown fat of the hamster.
  • 4.4. Our results show that AAT in the adult birds resembles white adipose tissue more than brown. Multilocularity of adipocytes may improve lipolysis to deliver fatty acids for muscle fuel of shivering or NST.
  相似文献   

17.
To examine whether cold-induced vascular endothelial growth factor (VEGF) gene expression in brown adipose tissue involved generation of hypoxic oxygen levels by thermogenic processes, we cold-exposed wild-type mice, as well as uncoupling protein-1 (UCP1)-ablated mice in which no thermogenesis in brown adipocytes can be induced. Cold exposure stimulated VEGF expression in both wild-type and UCP1-ablated mice. Unexpectedly, the effect was 3-fold higher in UCP1-ablated animals, whereas cultured brown adipocytes from both genotypes responded identically to norepinephrine stimulation. These results demonstrate that generation of low oxygen levels does not contribute to cold-induced VEGF expression in brown adipose tissue, but the results are consistent with an adrenergic regulation of expression.  相似文献   

18.
The adrenergic innervation of the urinary bladder of normal female and pregnant rats has been studied using a fluorescence histochemical method. The bladder is richly innervated by adrenergic nerve fibres as is evidenced by the presence of numerous adrenergic nerves in the adventitia, musculosa and submucosa. However, adrenergic nerve cells could not be observed. During pregnancy, adrenergic nerve fibres showed signs of degeneration, as most of the nerve fibres disappeared and the surviving fibres were much swollen. 10 days after parturition the pattern and density of adrenergic innervation became almost similar to those of the control animals.  相似文献   

19.
The bilateral lobe of interscapular brown adipose tissue of the Djungarian hamster was unilaterally denervated in order to study the role of the sympathetic innervation for maintenance and cold-induced increase of non-shivering thermogenesis. Denervation decreased the noradrenaline content of brown adipose tissue to less than 9% of the intact contralateral pad. This low noradrenaline level was maintained for 1–14 days after denervation. First, to study the role of the sympathetic innervation of brown adipose tissue in the maintenance of the high thermogenic capacity characteristic of the cold acclimated state, brown adipose tissue was denervated in hamsters either kept at thermoneutrality or acclimated to 5°C ambient temperature for 4 weeks. Cold-acclimated hamsters had elevated levels of uncoupling protein messenger ribonucleic acid (8.1-fold) and cytochrom-c oxidase-activity (3-fold). Denervation of brown adipose tissue decreased uncoupling protein-messenger ribonucleic acid level and cytochrom-c-oxidase-activity as compared to the intact pad in thermoneutral and in cold-acclimated hamsters. However, in cold-acclimated hamsters uncoupling protein-messenger ribonucleic acid level and cytochrom-c-oxidase-activity in denervated brown adipose tissue both were maintained on an elevated 6-fold higher levels as compared to thermoneutral controls. Second, to study the role of the sympathetic innervation of brown adipose tissue in the cold-induced increase in thermogenic capacity, hamsters were denervated prior to cold acclimation and responses were measured after 3 and 14 days of cold exposure. Uncoupling protein-messenger ribonucleic acid level and cytochrom-c-oxidase-activity of intact brown adipose tissue increased after 14 days cold acclimation. Denervation did not completely prevent a cold-induced 1.5-fold increase of cytochrom-c-oxidase-activity and a 3.2-fold increase of the uncoupling protein-messenger ribonucleic acid level in denervated brown adipose tissue after 14 days of cold acclimation. In conclusion, high levels of uncoupling protein-messenger ribonucleic acid and cytochrom-c-oxidase activity in brown adipose tissue of cold-acclimated hamsters can partially be maintained without intact sympathetic innervation, suggesting a considerable contribution of trophic factors not requiring sympathetic innervation for maintenance. The cold-induced increase of cytochrom-c-oxidase activity and expression of uncoupling protein-messenger ribonucleic acid largely depends upon sympathetic innervation of brown adipose tissue.Abbreviations ANOVA analysis of variance - BAT brown adipose tissue - COX cytochrom-c-oxidase - HPLC high performance liquid chromatography - mRNA messenger ribonucleie acid - NA noradrenaline - T a ambient temperature - UCP uncoupling protein  相似文献   

20.
The lean-to-fat ratio, that is, the relative masses of muscle and adipose tissue, is a criterion for the yield and quality of bovine carcasses and meat. This review describes the interactions between muscle and adipose tissue (AT) that may regulate the dynamic balance between the number and size of muscle v. adipose cells. Muscle and adipose tissue in cattle grow by an increase in the number of cells (hyperplasia), mainly during foetal life. The total number of muscle fibres is set by the end of the second trimester of gestation. By contrast, the number of adipocytes is never set. Number of adipocytes increases mainly before birth until 1 year of age, depending on the anatomical location of the adipose tissue. Hyperplasia concerns brown pre-adipocytes during foetal life and white pre-adipocytes from a few weeks after birth. A decrease in the number of secondary myofibres and an increase in adiposity in lambs born from mothers severely underfed during early pregnancy suggest a balance in the commitment of a common progenitor into the myogenic or adipogenic lineages, or a reciprocal regulation of the commitment of two distinct progenitors. The developmental origin of white adipocytes is a subject of debate. Molecular and histological data suggested a possible transdifferentiation of brown into white adipocytes, but this hypothesis has now been challenged by the characterization of distinct precursor cells for brown and white adipocytes in mice. Increased nutrient storage in fully differentiated muscle fibres and adipocytes, resulting in cell enlargement (hypertrophy), is thought to be the main mechanism, whereby muscle and fat masses increase in growing cattle. Competition or prioritization between adipose and muscle cells for the uptake and metabolism of nutrients is suggested, besides the successive waves of growth of muscle v. adipose tissue, by the inhibited or delayed adipose tissue growth in bovine genotypes exhibiting strong muscular development. This competition or prioritization occurs through cellular signalling pathways and the secretion of proteins by adipose tissue (adipokines) and muscle (myokines), putatively regulating their hypertrophy in a reciprocal manner. Further work on the mechanisms underlying cross-talk between brown or white adipocytes and muscle fibres will help to achieve better understanding as a prerequisite to improving the control of body growth and composition in cattle.  相似文献   

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