Vascular responses in canine subcutaneous adipose tissue to hypothalamic stimulation.

The present studies investigated vascular responses to electrical stimulation of the posterior hypothalamus in isolated but perfused and innervated subcutaneous adipose tissue in adult dogs. Three groups of dogs were distinguished: in one, electrical stimulation elicited vasodilation; in another, vasoconstriction, and in a third, neither significant vasodilation nor vasoconstriction occurred. Histological examination revealed that electrode placements were in the medial posterior hypothalamus, the lateral posterior hypothalamus, and the medial septal region, respectively. Hypothalamic stimulation failed to alter concentrations of free fatty acids or glycerol in venous blood from subcutaneous fat. Local beta-adrenergic block (propranolol) reversed the vasodilation to vasoconstriction while local alpha-adrenergic block (dihydroergotamine) abolished the vaso constrictor response. These results suggest that selective stimulation of the posterior hypothalamus results in neurogenic activation of both alpha- and beta-adrenergic mechanisms in adipose tissue vasculature. beta-Adrenergic vasodilation appears to predominate if the electrode is located medially, and alpha-adrenergic vasoconstriction appears to predominate if the electrode is located in the lateral posterior hypothalamus.     

Changes in ATP and cyclic nucleotide levels during sympathetic nerve stimulation in canine subcutaneous adipose tissue in situ.

Subcutaneous adipose tissue in fed, female dogs was isolated. Biopsies of the tissue (30-150 mg) were taken and rapidly frozen in liquid nitrogen before, during and after nerve stimulation (3-4 Hz). In unstimulated adipose tissue the levels of ATP1 were 74+/-7 nmol/g, of cyclic AMP 90 +/- 12 pmol/g and of cyclic PGMP 18 +/- 3 pmol/g (mean+/-S.E.). During sympathetic nerve stimulation the levels of ATP and cyclic GMP fell by 30 and 50% respectively (p less than 0.01), while the cyclic AMP content increased by 50% (p less than 0.05). After nerve stimulation there was a marked increase in glycerol release, and the levels of all three nucleotides returned to control. The fall in ATP during nerve stimulation was essentially eliminated by prior adrenergic alpha-receptor blockade. It is concluded that 1) sympathetic nerve stimulaton induces a rapid, reversible fall in tissue ATP content, which may be related to hypoxia secondary to the vasoconstriction, and 2) lipolytic responses to sympathetic nerve stimulation in vivo are preceeded by small increases in the tissue cyclic AMP level, and a 3-fold increase in the cyclic AMP/cyclic GMP ratio.     

Effect of reflex stimuli on vascular resistance and glycerol release in in vivo dog subcutaneous adipose tissue

Summary Although direct autonomic nerve stimulation and infusion of catecholamine has been shown to result in substantial amounts of lipolysis in dog subcutaneous adipose tissue, there is no evidence to indicate that reflex autonomic stimulation will result in qualitatively and quantitatively similar changes. The present studies were, performed to evaluate the effects of reflex autonomic stimulation on vascular resistance and glycerol release in isolated, innervated and blood-perfused subcutaneous fat pad. Autonomic nerve stimulation at physiological frequencies was performed and resulted in release of glycerol that was compatible with previously reported data. Reflex stimulation by moderate and severe hypoxemia did not result in a significant glycerol release, but a maximal reflex stimulus (ventricular fibrillation) did. Since the majority of these reflex stimuli resulted in large changes in vascular resistance, it would appear that reflex hemodynamic changes can occur in these preparations without concommitant changes in glycerol release. Alpha blockade of the vasoconstriction resulted in the appearance of rising glycerol output suggesting that vasoconstriction prevents lipolysis.Supported by: American Heart Association Grant 72-615 and NIH, Medical Cardiology Training Grant HL05635 (Drs. Croke and Longo) and by USPHS Career Developement Award I KOY HF46346 (Dr. Skinner).     

脂肪组织工程研究进展

组织工程为临床疑难问题的解决提供了新的思路 ,而工程化脂肪组织具有组织重建与填充作用 ,广泛应用于外科领域。本文就脂肪组织工程涉及的前脂肪细胞生长分化、分子调控、聚合物支架及细胞外基质、微环境等方面进行综述     

The antilipolytic effect of endogenous and exogenous adenosine in canine adipose tissue in situ

The effects of adenosine, 2-Cl-adenosine, two adenosine uptake inhibitors (dipyridamole and dilazep) and the adenosine deaminase (ADA) inhibitor erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA) were studied on basal and stimulated lipolysis in subcutaneous adipose tissue. The basal lipolysis was unaffected by all agents. Lipolysis induced by nerve stimulation (4 Hz, 5 min) was dose-dependently antagonized (up to 100%) by close i.a. infusions of adenosine (1–40 μM in blood); if the nerve induced vasoconstriction was prevented by α-adrenoceptor-blockade. 2-Cl-adenosine was a more potent antilipolytic agent than adenosine. EHNA (3–10 μM in blood) did not inhibit stimulated lipolysis in vivo possibly because of the low ADA activity in fat cells. Dipyridamole (0.5-1.5 μM in blood) in combination with EHNA increased the venous plasma concentration of adenosine from 0.3±0.05 to 0.7±0.1 μM and enhanced the tissue concentration close to 3-fold. Lipolysis induced by nerve stimulation (4 Hz) was reduced by about 40% by dipyridamole + EHNA and that induced by close i.a. noradrenaline injection (20 nmol) by approximately 60%. It is concluded that adenosine is an antagonist of stimulated lipolysis in subcutaneous adipose tissue in situ in concentrations that are reached during prolonged sympathetic nerve stimulation.     

Resistin increases islet blood flow and decreases subcutaneous adipose tissue blood flow in anaesthetized rats

Aim: Resistin is an adipokine which has been suggested to participate in the induction of insulin resistance associated with type 2 diabetes. The aim of the present study was to investigate whether acute administration of resistin influences tissue blood perfusion in rats. Methods: Resistin was administered as an intravenous infusion of 7.5 μg h^?1 (1.5 mL h^?1) for 30 min to rats anaesthetized with thiobutabarbital. A microsphere technique was used to estimate the blood flow to six different depots of white adipose tissue (WAT), brown adipose tissue (BAT), as well as to the pancreas, islets, duodenum, colon, kidneys, adrenal glands and liver. Results: Resistin administration led to an increased blood flow to the pancreas and islets and a decrease in subcutaneous WAT and BAT. Intra‐abdominal white adipose tissue blood flow and that to other organs were not affected. Conclusion: Acute administration of resistin markedly affects the blood perfusion of both the pancreas and subcutaneous white adipose tissue depots. At present it is unknown whether resistin exerts a direct effect on the vasculature, or works through local or systemic activation of endothelial cells and/or macrophages. The extent to which this might contribute to the insulin resistance caused by resistin is yet unknown.     

Influence of adenosine on responses to vagal nerve stimulation in the anesthetized rabbit

The influence of local adenosine infusion into the celiac artery on the gastric contractile responses to centrifugal vagal nerve stimulation was studied in anesthetized rabbits, and was compared with the effects of systemic administration of equivalent amounts of adenosine. Close arterial infusion of adenosine caused a marked reduction of gastric contractions induced by nerve stimulation, whereas corresponding responses to close arterial infusions of acetylcholine were enhanced during adenosine. The comparison with systemic adenosine administration revealed that the influence on gastric neurotransmission was not related to the hypotensive effect of the compound. No effects of adenosine were seen on bronchial activity as measured by insufflation pressure. Variable effects were obtained on cardiac responses to vagal stimulation. Gastric smooth muscle contractions elicited in vitro by transmural nerve stimulation were affected by adenosine in a biphasic manner, initial inhibition followed by potentiation of the apparently cholinergic responses. It is suggested that adenosine may modulate cholinergic neurotransmission in vivo by a dual effect, prejunctional inhibition and postjunctional enhancement.     

Effect of ventromedial hypothalamic stimulation on blood flow of brown adipose tissue in rats

The changes in regional blood flows to the rat's interscapular brown adipose tissue and several other tissues during electrical stimulation of the ventromedial hypothalamus (VMH) were studied using radioactively labelled microspheres. Measurement of blood flow was carried out, along with monitoring heart rate, under anesthesia and at thermoneutrality. During VMH stimulation the heart rate was clearly augmented and cardiac output increased about 45%. Regional blood flows were significantly increased in response to VMH stimulation in interscapular brown adipose tissue, adrenal glands, diaphragm and gastrocnemius muscles. The response of interscapular brown adipose tissue was the most prominent (approx. fiftyfold increase). Blood flows tended to decrease in spleen, lungs and kidneys during VMH stimulation, but did not change in liver or in other visceral organs. These observations suggest that the VMH is concerned with the regulation of regional blood flow to brown adipose tissue and contributes to thermogenesis in this tissue.     

Ⅱ型固有淋巴细胞在白色脂肪棕色化中的作用

正Ⅱ型固有淋巴细胞(typeⅡinnate lymphoid cells,ILC2s)于2001年被发现,由共同淋巴样祖细胞发育而来,广泛分布在血液、肠道、气管、肺脏、脾脏、肝脏、动物脂肪和皮肤等部位,经白细胞介素(interleukin,IL)-25或IL-33刺激后可产生IL-5和IL-13等2型辅助性T(type 2 helper T,Th2)细胞因子,在Th2     

Dissociation between brown adipose tissue thermogenesis and sympathetic activity in rats with high plasma levels of oestradiol

It has been shown previously that high plasma levels of oestradiol inhibit brown adipose tissue thermogenesis. Since rats and mice show a close association between thermogenic activity in and sympathetic discharge to brown fat, we measured the noradrenaline turnover in rats with high plasma levels of oestradiol to establish whether the observed inhibition of thermogenic activity is brought about by a reduction in the sympathetic drive to brown adipocytes. Oestradiol-filled Silastic capsules were implanted subcutaneously in female rats previously acclimated either to thermoneutrality or to cold. Control rats received empty implants. After 15 days treatment, noradrenaline turnover was measured by blocking its synthesis with -methyl-p-tyrosine. As expected, noradrenaline turnover was higher in cold-acclimated rats than in rats kept at thermoneutrality. The presence of high plasma oestradiol levels did not alter sympathetic activity in any of the treated groups despite reducing thermogenic activity. This result reveals that oestradiol dissociates the thermogenic activity of brown adipose tissue from its sympathetic activation. Such dissociation has never been previously reported in rats, although it seems to be common in Syrian hamsters. However the causative factor in this species is unknown.A preliminary report of this work was presented to the XXXIIth International Congress of Physiological Sciences, Glasgow, August 1993 and appears as abstract No. 287.6/P.     

大鼠白色和棕色脂肪来源的间充质干细胞成脂分化特性的比较

目的探讨白色脂肪组织(WAT)和棕色脂肪组织(BAT)来源的间充质干细胞成脂分化特性的差异。方法雄性SD大鼠15只,3只用于细胞分离培养,12只用于细胞移植。体外分离培养WAT和BAT两种来源的脂肪干细胞,用油红O染色检测两种干细胞的成脂分化率,用免疫荧光技术检测成脂诱导、分化后的细胞是棕色脂肪细胞还是白色脂肪细胞。4’6-二脒基-2-苯基吲哚(DAPI)标记两种来源的干细胞后移植至腹股沟区,分别在第1、2、3周取材,免疫荧光技术检测植入细胞的分化趋向。结果 WAT来源的干细胞增殖速度明显快于BAT来源的干细胞,前者成脂分化率为0.205±0.069,后者为0.165±0.053,两种干细胞的成脂诱导率差异无统计学意义(P0.05)。两种干细胞分别植入体内后,在第1、2、3周发现,两种干细胞均表达棕色脂肪特异性蛋白解耦联蛋白1(UCP1)。结论 WAT和BAT来源的干细胞在体外及体内诱导成脂后均分化为棕色脂肪细胞。