Effects of beacon on the rat pituitary-adrenocortical axis response to stress

Beacon is a peptide expressed in the rat hypothalamus and adrenal cortex, which is involved in the central regulation of feeding and inhibits basal and agonist-stimulated glucocorticoid secretion from adrenocortical cells. In vivo studies on beacon have not yet been carried out, and therefore we investigated the effects of a subcutaneous (sc) injection of beacon on the response of rat hypothalamo-pituitary-adrenal axis to stress. Handling and sc injection per se elicited a moderate increase in the plasma concentrations of ACTH and corticosterone, which was counteracted by beacon. Similarly, beacon dampened ACTH and corticosterone responses to ether stress. In contrast, beacon did not affect ACTH response to cold stress, although it was able to induce a moderate lowering in the corticosterone response. Taken together, these findings allow us to draw the following conclusions: i) beacon inhibits handling/injection- and ether stress-activated, but not cold stress-activated, neural mechanism(s) responsible for stimulation of ACTH secretion and the ensuing increase in corticosterone production; and ii) the beacon-induced dampening in corticosterone response to stress also involves a direct inhibitory effect on the adrenal-cortex secretory activity. The physiological relevance of beacon as endogenous anti-stress agent remains to be evaluated.     

Effects of chronic central leptin infusion on proopiomelanocortin and neurotensin gene expression in the rat hypothalamus

Leptin signaling in the hypothalamus is critical for normal food intake and body weight regulation. While hyperleptinemia in obese people suggests a state of leptin resistance, the mechanism is not clearly understood. In a rat model of central leptin infusion in which animals develop resistance to the satiety action of leptin, orexigenic peptide producing neuropeptide Y neurons in the hypothalamus develop leptin resistance. However, it is still unknown if increased hypothalamic leptin tone caused by central leptin infusion results in the development of leptin resistance in anorexigenic peptide producing proopiomelanocortin (POMC) and neurotensin (NT) neurons. To this end, male rats were infused chronically with leptin (160 ng/h) or vehicle into the lateral cerebroventricle for 16 days. On day 4 of leptin infusion when food intake was decreased, POMC and NT mRNA levels, as determined by RNAse protection assay, were significantly increased as compared to control. By contrast, on day 16 of leptin infusion, when food intake was mostly normalized, both POMC and NT mRNA levels remained unchanged compared with control. These findings suggest the development of leptin resistance in the POMC and NT neurons following chronic elevation of hypothalamic leptin tone, which may be involved in the development of resistance to the satiety action of leptin following central infusion of this peptide hormone.     

Effects of prolonged voluntary wheel-running on muscle structure and function in rat skeletal muscle

We examined the effects of prolonged voluntary wheel-running on skeletal muscle functional and/or structural characteristics in rats. Male Sprague-Dawley rats (5 weeks old) were divided into five groups: (1) 15W-SC, sedentary controls housed in normal plastic cages until age 15 weeks; (2) 15W-VE, housed in a voluntary-exercise (running-wheel) device equipped with housing space until age 15 weeks; (3) 35W-SC, housed in normal plastic cages until age 35 weeks; (4) 35W-VE, housed in the voluntary-exercise device until age 35 weeks, and (5) 35W-MVE, housed in normal plastic cages until age 15 weeks, then in the voluntary-exercise device from age 16 weeks to 35 weeks (middle age). At the end of each rats experimental period, the plantaris muscle was dissected from each hindlimb for analysis of the muscles functional and/or structural characteristics. Total running distance was similar in 15W-VE and 35W-VE, both being significantly greater than in 35-MVE. The percentage of type IIb myosin heavy chain isoform was significantly lower in each VE group than in the corresponding SC group. This shift from type IIb was significantly greater for 35W-VE than for the other VE groups, which were similar to each other. The cross-sectional area of type IIx fibers was significantly greater in 35W-VE than in 35W-SC, but this was not true for 15W-VE versus 15W-SC or for 35W-MVE versus 35W-SC. No significant difference in citrate synthase activity was detected between any VE group and the corresponding SC group. These results suggest that a prolongation of voluntary wheel-running leads to some advantageous enhancements of functional and/or structural characteristics in rat plantaris.     

Effect of prolonged angiotensin II infusion on thirst.

To determine the effect of prolonged angiotensin II (A-II) infusion on thirst, daily water intake by drinking was measured in dogs during a 4-day control period, a 4-day period of vehicle infusion without A-II, a 10-day period of A-II infusion, and a 4-day recovery period of vehicle infusion without A-II. During the control period and the periods of vehicle infusion in the absence of A-II, daily water intake by drinking in four dogs averaged 118 +/- 20 ml/day (mean +/- SE). During the 10-day period of A-II infusion at the rate of 13.0 ng/kg per min drinking increased to 269 +/- 49 ml/day (paired t; P less than 0.05). Angiotensin II infusion at the rate of 26.0 ng/kg per min produced a sustained increase in water intake in two dogs during an 8-day period of infusion. These results demonstrate that in dogs, prolonged infusion of angiotensin II stimulates the thirst mechanism and that the effect lasts for more than a few days.     

Effects of continuous lumbar intrathecal infusion of leptin in rats on weight regulation

Intracranial leptin alters food consumption and body weight. To systematically characterize the effects of extended continuous spinal intrathecal delivery on such regulation, female rats received continuous lumbar spinal infusion (14 days) through catheters connected to osmotic minipumps of a vehicle or one of several doses of recombinant murine leptin (0.03–10 μg/day). The following observations were made. (1) Leptin resulted in a dose-dependent suppression in body weight and food consumption at doses above 0.3 μg/day. (2) Food consumption was initially reduced. Weight fell for 7 days and then plateaued at a level proportional to dose. (3) The ratio of food consumed to body weight was constant for control animals across the study. Leptin-infused rats slowed the initial fall in weight by increasing food consumption, such that the food to body weight ratio returned to that of control values. Rats were thus regulating food consumption to sustain body weight as defined by leptin dose. (4) On day 14, cisternal cerebrospinal fluid was obtained and leptin measured. Concentrations covaried in a log linear fashion with infusion dose. Body weight and food consumption covaried similarly with cisternal leptin concentrations across dose groups.

Our data suggest that steady state infusions of leptin induce a degree of appetite suppression that leads to a steady state level of body weight loss and not simply to a simple block of consumatory behavior. The unexpected potency of the observed effects of intrathecal leptin relative to doses that are required after i.c.v. delivery suggests that at least a portion of the effects of intrathecal leptin may reflect a medullary action. The observed correlation of cisternal leptin levels with the behavioral effects is also consistent with a reliable distribution of the infused leptin to target supraspinal sites.     

Effects of proadrenomedullin N-terminal 20 peptide on the rat pituitary-adrenocortical axis under basal and stressful conditions

Proadrenomedullin N-terminal 20 peptide (PAMP) derives, along with adrenomedullin (AM), from prepro-AM. AM has been reported to modulate the activity of the hypothalamic-pituitary-adrenal (HPA) axis, and this study aimed at ascertaining whether PAMP exerts similar effects. PAMP was subcutaneously administered to non-stressed and stressed rats, and the plasma concentrations of ACTH and corticosterone were measured by radioimmune assay. In non-stressed rats, PAMP raised ACTH and corticosterone blood levels at 60 min, and ACTH plasma concentration at 120 min. Ether and cold stresses increased the plasma levels of both ACTH and corticosterone, and PAMP dampened HPA axis response to cold stress, without affecting that to ether stress. The conclusion is drawn that PAMP i) stimulates rat HPA axis, through a mechanism similar to that of ether stress; and ii) interferes with the neural pathways involved in the cold stress-induced activation of HPA axis.     

瘦素的生物学功能

瘦素的发现是基于对肥胖基因的研究,最初使它受关注的是它减少动物摄食和降低体内脂肪沉积的作用.然而近年来对它的一系列研究已远远超出了这个单一的领域,瘦素对肝肾等全身多种重要器官生理的活动、整体水平的糖脂代谢甚至机体生长发育的调控作用被陆续发现.虽然其中仍有许多机制待阐明,但各种研究成果不断.本文主要归纳介绍瘦素调节脂肪代谢的基本作用及其对骨骼、神经、消化、心血管以及内分泌系统的调控作用的一些较重要的研究发现,并对其机制作初步探讨.     

Effects of prolonged administration of chlorphentermine on the rat lung

Prolonged administration of the anorexigen chlorphentermine hydrochloride to young male Wistar albino rats for up to one year failed to induce in them either right ventricular hypertrophy or hypertensive pulmonary vascular disease. There was, however, the development of a pronounced pulmonary histiocytosis. Studies by light and electron microscopy showed that these histiocytes disintegrated to liberate their lamellar inclusions into the alveolar spaces, producing a picture reminiscent of alveolar proteinosis. Fibrosing alveolitis occurred in only one animal and was thought to be related to inflammatory changes rather than as a development of the pulmonary histiocytosis. Attention is drawn to the fact that thick-walled large pulmonary arteries are entirely normal in rats and should not be misinterpreted as evidence of hypertensive pulmonary vascular disease in test animals.     

Effects of intracerebroventricularly administered leptin on protein selection in the rat

The effect of centrally administered rat leptin on selection of 5 and 30% protein diets was investigated in male Sprague-Dawley rats with indwelling i.c.v. cannulas. Leptin (0 vs 2.5 microg/day) was administered for 4 consecutive days, followed by an 8-day withdrawal period. Total intake was reduced to approximately 50% of that in the vehicle injected group during each day following leptin administration. Intake of both the 5 and 30% diets was reduced. Vehicle-treated rats selected a 13-15% CP diet. Diet selection in leptin-treated rats was not different during the first day, but on Days 2-4, leptin-treated rats selected a 10% CP diet. Intake began to normalize within 24-48 h after the last treatment, and was not different by Day 3 of the withdrawal period. Body weight was reduced by leptin treatment, and despite the normalization of food intake, did not recover during the withdrawal period. Rats were sacrificed at the end of the 8-day withdrawal period. Despite the reduction in body and carcass weights, liver, kidney, heart, and soleus muscle weights were not different between control and leptin-treated groups when expressed on an absolute or relative basis. However, epididymal and retroperitoneal fat pad weights were still reduced 56 and 78%, respectively, in rats that had been previously treated with leptin for 4 days and then not treated for 8 days. In addition, circulating T3 levels remained elevated in rats that had been treated with leptin. Centrally administered leptin has little effect on muscle mass, but had potent effects on intake of nonobese rats and a sustained effect on adipose tissue mass, thyroid hormone status, and body weight after withdrawal. Results from rats selecting between diets varying in protein content suggest that leptin may cause avoidance of protein.     

Effects of glucose ingestion or glucose infusion on fuel substrate kinetics during prolonged exercise

To determine if bypassing both intestinal absorption and hepatic glucose uptake by intravenous glucose infusion might increase the rate of muscle glucose oxidation above 1 g · min^–1, ten endurance-trained subjects were studied during 125 min of cycling at 70% of peak oxygen uptake (VO_{2 peak}). During exercise the subjects ingested either a 15 g · 100 ml^–1 U-¹⁴C labelled glucose solution or H₂O labelled with a U-¹⁴C glucose tracer for the determination of the rates of plasma glucose oxidation (Rox) and exogenous carbohydrate (CHO) oxidation from plasma¹⁴C glucose and¹⁴CO₂ specific activities, and respiratory gas exchange. Simultaneously, 2-³H glucose was infused at a constant rate to measure glucose turnover, while unlabelled glucose (25% dextrose) was infused into those subjects not ingesting glucose to maintain plasma glucose concentration at 5 mmol · l^–1. Despite similar plasma glucose concentrations [ingestion 5.3 (SEM 0.13) mmol · l^–1; infusion 5.0 (0.09) mmol · l^–1], compared to glucose infusion, CHO ingestion significantly increased plasma insulin concentrations [12.9 (1.0) vs 4.8 (0.5) mU · l^–1;P<0.05], raised total Rox values [9.5 (1.2) vs 6.2 (0.7) mmol · 125 min^–1 kg fat free mass^–1 (FFM);P<0.05] and rates of CHO oxidation [37.2 (2.8)vs 24.1 (3.9) mmol · 125 min^–1 kg FFM^–1;P<0.05]. An increased reliance on CHO metabolism with CHO ingestion was associated with a decrease in fat oxidation. Whereas the contribution from fat oxidation to energy production increased to 51 (10)% with glucose infusion, it only reached 18 (4)% with glucose ingestion (P<0.05). Despite these differences in plasma insulin concentration and rates of fat oxidation, the rates of glucose oxidation by muscle were similar after 125 min of exercise for both trials [ingestion 93 (8); infusion 85 (5) mol · min^–1 kg FFM^–1], suggesting that peak rates of muscle glucose oxidation were primarily dependent on blood glucose concentration which, in turn, regulated the hepatic appearance of ingested CHO.     

Effects of leptin and leptin fragments on steroid secretion and proliferative activity of regenerating rat adrenal cortex

Leptin, an adipose tissue-secreted hormone, acts via several isoforms of specific receptors (Ob-Rs), which may variously interact with the native leptin molecule and its fragments. Evidence has been provided that leptin affects rat adrenal functions, but the results were rather conflicting depending on the experimental condition examined (e.g. regenerating vs. mature or immature adrenal gland). Hence, we investigated the effects of three subcutaneous injections of murine leptin(1-147) and several leptin fragments (3 nmol/100 g body weight; 28, 16 and 4 h before the sacrifice) on the secretory activity and growth of regenerating rat adrenal cortex. The following leptin fragments were tested: murine leptin(116-130), and human leptin fragments 150-167, 138-167, 93-105, 22-56 and [Tyr]26-39. Leptin(1-147) enhanced plasma concentration of both aldosterone and corticosterone. The blood level of aldosterone was raised by leptin(116-130), leptin(138-167) and leptin(93-105), and that of corticosterone by leptin(93-105) and Tyr-leptin(26-39). Metaphase index (stachmokinetic method with vincristine) was unaffected by leptin(1-147), and lowered by leptin(116-130), leptin(150-167) and leptin(138-167). Collectively, our findings allow us to conclude that leptin and leptin fragments enhance the secretory activity and inhibit the growth of regenerating rat adrenal cortex, the biological activity of leptin being located in the C-terminal segment of its molecule.     

Effects of prolonged adrenaline infusion and of mental stress on plasma minerals and parathyroid hormone

The role of the sympatho-adrenal system for the secretion of PTH in humans is not established. Previous studies on the effects of adrenaline on plasma mineral homeostasis have focused on injections or short-term infusions of adrenaline, and conflicting results concerning calcium and parathyroid hormone (PTH) responses have been reported. We therefore infused adrenaline or placebo continuously for 3 h to 10 healthy volunteers and studied several plasma minerals, as well as PTH levels. Venous plasma adrenaline concentrations increased to the upper physiological range (5 nmol l-1) during adrenaline infusion. Another nine volunteers were exposed for 25 min to mental stress (a colour word conflict test; CWT), which causes marked circulatory changes and raises plasma catecholamine concentrations. Plasma ionized and total calcium, and magnesium concentrations were slowly and gradually reduced during infusion of adrenaline, but there was only a small increase in PTH. Plasma potassium was decreased by adrenaline within 30 min and thereafter did not change further during infusion. There was a marked but transient increase in the plasma free fatty acids concentration, which were not related to the reduction of the calcium or magnesium levels. The adrenaline-induced decrements in calcium, magnesium and potassium, and increases in heart rates persisted 30 min after the infusion, despite a rapid decrease in plasma adrenaline concentrations within 5 min of termination of the infusion. Plasma phosphate concentrations were lowered during the first 90 min of adrenaline infusion, but after 3 h they had returned to baseline despite continued infusion. CWT induced small increments of the plasma ionized calcium and PTH concentrations. Plasma potassium levels were raised despite increases in plasma adrenaline at the beginning of the stress test, while phosphate values were reduced at the end of the test. Thus, long-lasting elevations of circulating adrenaline lower plasma ionized and total calcium, phosphate, magnesium and potassium, but the time courses for these changes differed markedly. Despite the reduction of plasma ionized calcium there was only little increase in PTH and thus no indication that sustained elevations of circulating adrenaline stimulates the secretion of PTH in vivo in humans. Responses to acute mental stress and adrenaline infusion differed qualitatively, indicating that adrenaline responses to stress are of minor importance in this respect.     

瘦素在糖代谢中的作用与机制

瘦素是重要的脂肪细胞因子。近年发现瘦素及其受体参与了胰岛素抵抗(IR)。瘦素本身可造成脂肪组织的IR，减少脂肪合成，增加脂肪分解，从而引起肝脏和肌肉的IR，使胰岛素依赖的糖处理效率受到削弱，与2型糖尿病的形成与发展密切相关。     

瘦素对生殖调节的研究进展

近年来 ,肥胖机制的研究不断深入 ,先后完成了肥胖基因 (ｏｂｅｓｅｇｅｎｅ ,ｏｂｇｅｎｅ )的克隆 ,肥胖基因产物———瘦素 (ｌｅｐｔｉｎ )的发现 ,以及ｌｅｐｔｉｎ受体基因的克隆。Ｌｅｐｔｉｎ最初是作为调节机体重量平衡的因子被认识的。它由脂肪组织产生 ,分泌 ,进入血流 ,到达下丘脑 ,传递体内脂肪含量的信号给中枢神经系统 ,从而抑制摄食 ,增加能量消耗 ,进而减轻体重 ,控制能量平衡。随着研究的加深 ,人们发现 ,ｌｅｐｔｉｎ在生殖方面有许多重要的调节作用。本文综述ｌｅｐｔｉｎ对生殖的调节作用。1　肥胖基因及其产物195 0年…