中药纤体组方加左旋肉碱酒石酸盐的减肥作用及对血糖的影响

目的探讨中药纤体组方(XTA)和中药纤体组方加左旋肉碱酒石酸盐(XTB)对营养性肥胖大鼠的减肥作用及对血糖的影响。方法通过高脂饲料饮食建立营养性肥胖大鼠模型,观察体质量、摄食量、脂肪质量、体长、Lee′s指数和空腹血糖、糖耐量来评价受试品对肥胖大鼠的影响。结果造模后高脂组大鼠的体质量显著高于正常组(P<0.05),提示造模成功;与模型组相比,XTA高剂量组大鼠体质量显著降低(P<0.05);低、中、高剂量组脂肪质量、Lee′s指数显著降低(P<0.05)。与模型组相比,XTB中、高剂量组大鼠的体质量显著降低(P<0.05);低、中、高剂量组大鼠脂肪质量、Lee′s指数显著降低(P<0.05)。糖负荷60min时,XTA低、中剂量组大鼠的血糖含量低于模型组(P<0.05);糖负荷120min时,XTB中剂量组血糖含量显著低于模型组(P<0.05)。结论中药纤体组方加左旋肉碱酒石酸盐对营养性肥胖大鼠有减肥作用,并具有调节血糖的作用,且XTB有优于XTA的趋势。     

吴茱萸碱对肥胖并发血管肥厚的作用研究

目的研究吴茱萸碱对大鼠肥胖症及并发血管肥厚的预防作用。方法高脂饮食诱导肥胖大鼠模型;形态测量法动态观察大鼠体重、体长和Lee’s指数;ELISA法测定大鼠血清和组织降钙基因相关肽(CGRP)含量;免疫组化测定血管组织和背根神经节(DRG)TRPV1表达;比色法测定大鼠血清总胆固醇、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇和甘油三酯含量。结果吴茱萸碱和辣椒素干预大鼠13周后,降低肥胖大鼠体重和Lee’s指数,降低肥胖大鼠内脏脂肪重量和内脏脂肪重量指数,并降低肥胖大鼠血清总胆固醇和甘油三酯含量。吴茱萸碱能逆转肥胖并发的血管肥厚;与正常大鼠相比,肥胖大鼠胸主动脉组织和DRG中TRPV1表达降低,血清和腹主动脉CGRP增加。吴茱萸碱和辣椒素能增加胸主动脉组织和DRG中TRPV1的表达;吴茱萸碱能降低血清和腹主动脉中CGRP含量。结论吴茱萸碱对高脂饮食诱导的肥胖具有良好的预防作用,其作用机制可能与调节血清、血管组织和DRG中CGRP和TRPV1的表达有关,其具体机制值得进一步的深入研究。     

大豆黄素衍生物LRXH609的减肥作用及机理探讨

目的：探讨大豆黄素衍生物IRXH609（LRX）的减肥作用和可能的机理。方法：以高脂饮食诱导肥胖大鼠,测量体重、Lee’s指数、腹腔脂肪重量、摄食量、血脂和血糖,检验LRX灌服30d后的减肥效果;体外培养诱导分化3T3-L1前脂肪细胞,观察药物对脂肪细胞增殖、脂质合成和分解的影响。结果：LRX显著降低高脂饮食诱导的肥胖大鼠体重、Lee’s指数、腹腔脂肪重量;降低血液中TC和游离脂肪酸（FFA）含量;抑制3T3-L1前脂肪细胞增殖;显著提高3T3-L1前脂肪细胞内激素敏感脂酶（HSL）活性,促进脂肪分解释放甘油（Gly）,减少细胞内TG含量。结论：LRXH609有显著的减肥和调血脂作用,可能的机理是通过抑制前脂肪细胞增殖和分化,激活HSL促进脂肪细胞内TG分解,降低脂肪细胞内TG存储量。     

甘草甜素对实验性肥胖大鼠减肥作用及机制探讨

目的探讨甘草甜素（glycyrrhizin）的减肥作用及其可能的作用机制。方法高脂饮食诱导肥胖大鼠模型,通过测量体重、Lee＇s指数、腹腔脂肪分布及重量、摄食量、血脂和血糖,检验甘草甜素灌服4周后的减肥效果;体外培养诱导分化3T3-L1前脂肪细胞,观察药物对脂肪细胞增殖,脂质合成和分解的影响。结果甘草甜素能显著降低高脂饮食诱导的肥胖大鼠体重和Lee’s指数,使其腹腔脂肪减少,降低血液中胆固醇（TC）和游离脂肪酸（FFA）含量,抑制前脂肪细胞增殖,促进脂肪分解,减少甘油三酯（TG）堆积。结论甘草甜素有显著的减肥和调血脂作用,其可能的机制是抑制前脂肪细胞增殖和分化,促进细胞内脂肪分解,降低脂肪细胞内TG存储量。     

茶多酚对奥氮平诱导肥胖大鼠的减肥作用及其机制

目的探讨茶多酚对奥氮平诱导肥胖大鼠的减肥作用及其机制。方法 SD雌性大鼠50只,随机分为正常对照组(10只)和奥氮平诱导肥胖模型组(40只)。肥胖模型组于黑暗时相前1h奥氮平1.2 mg·kg~(-1)·d~(-1)灌胃,正常对照组给予等容量蒸馏水,连续2 wk。于wk 3开始,再将肥胖模型大鼠随机分为4组:模型组、西布曲明(2.5 mg·kg~(-1)·d~(-1))组、茶多酚低(150 mg·kg~(-1)·d~(-1))剂量组和茶多酚高(300 mg·kg~(-1)·d~(-1))剂量组,每组10只。连续给药5 wk。观察大鼠体重、肾和子宫周围脂肪湿重,计算Lee's指数和脂肪系数,测定血清瘦素、脂联素水平以及超氧化物歧化酶(SOD)活性和丙二醛(MDA)含量。结果与正常对照组相比,模型组大鼠体重和脂肪湿重及Lee's指数和脂肪系数均增加,血清瘦素水平升高,脂联素水平降低(P<0.05)。与模型组比较,茶多酚低、高剂量组大鼠体重和脂肪湿重降低,Lee's指数、脂肪系数降低,SOD活性增加,MDA含量减少(P<0.05)。与模型组比较,茶多酚高剂量组血清脂联素水平升高(P<0.05),瘦素水平无显著差异(P>0.05)。结论茶多酚对奥氮平诱导的肥胖大鼠有减肥作用,其作用机制可能与增强脂联素的调节和提高抗氧化能力有关。     

针刺对单纯性肥胖大鼠下丘脑神经肽Y mRNA表达的影响

针刺具有明显的减肥效应，已在临床运用和实验研究中得到广泛证实。研究显示能量摄入(摄食)与消耗的精细平衡是保持正常体重的关键，肥胖是最常见的能量失衡状态，而下丘脑是调节摄食行为和能量平衡的关键部位。本文拟通过针刺对肥胖大鼠下丘脑神经肽Y(NPY)和瘦素(Leptin)受体(OB-Rb)mRNA表达的影响研究，探讨针刺对食源性肥胖大鼠下丘脑能量调节网络的干预作用。     

茶多酚对抗精神病药物奥氮平诱致肥胖大鼠作用与机制研究

目的探讨茶多酚对抗神经病药物奥氮平诱致肥胖大鼠的作用以及机制。方法本次研究选取64只健康的雌性大鼠作为研究对象,对其进行茶多酚对抗神经病药物奥氮平治疗,观察其对大鼠肥胖的作用以及机制。结果模型对照组和正常组进行比较,发现大鼠在体重、食物的摄取量、Lee’s指数、脂肪系数、脂肪湿重、5-HT、DA、DOPAC含量、血清瘦素含量、FFA含量方面均有所增加,夜晚距离和平均速度、脂联素含量明显降低,相比差异具有统计学意义(P<0.05);饮水量、白天自主行为、夜晚慢速运动时间和快速运动时间及休息时间、TC、TG、LDL-C、HDL-C含量、血糖、胰岛素含量、ALT、AST、SOD活性、MDA含量无明显变化,相比差异均无统计学意义(P>0.05);高剂量和低剂量组与模型对照组相比,在体重、饮食量、饮水量、白天休息时间、Lee’s指数、脂肪系数、脂肪湿重、DA、DOPAC含量、FFA含量、LDL-C含量、血糖、胰岛素含量、ALT、AST、MDA含量方面均有所减少,相比差异具有统计学意义(P<0.05);5-HT含量、血清瘦素含量无明显变化,相比差异均无统计学意义(P>0.05);白天时距离和快速运动时间及平均速度、夜晚距离和平均速度、5-HIAA、NA含量、脂联素含量、SOD活性明显增加,相比差异具有统计学意义(P<0.05);其中低剂量组夜晚快速运动的时间显著增加,并且休息的时间相对减少,体内TC含量降低,相比差异具有统计学意义(P<0.05)。结论茶多酚能够有效的抑制肥胖大叔的食物摄取量,减少了它的饮水和进食量,引导肥胖大鼠多进行自主活动,缩短了其休息时长,增加在黑暗时的运动量以及运动速度,促进下丘脑递质对5-HT的诱导分泌,拉升5-HIAA和NA水平,降低DA的水平,抑制食欲提高了运动量,通过脂肪细胞因子的调节,体内血清脂联素的含量增加,并且体美高脂肪酸的氧化程度和能量消耗更多,脂代谢速度加快,体内FFA、LDL-C和TC的含量明显降低,在提升SOD活性的同时,降低MDA的含量,达到提升机体抗氧化能力的效果。     

加味苓桂术甘汤对奥氮平诱导肥胖大鼠的减肥作用及其机制

目的:探讨加味苓桂术甘汤(LGSG)对奥氮平诱导肥胖大鼠的减肥作用及其机制。方法:SD雌性大鼠70只,取其中10只为对照组,其余60只ig奥氮平2周。将造模成功的40只肥胖大鼠随机分为模型组、盐酸西布曲明组、LGSG低、高剂量组,每组10只。动物继续ig奥氮平,同时ig上述药物5周,利用SMART video-tracking system测定大鼠黑暗时相的自主活动,并于药物处理结束时测定大鼠体质量、Lee's指数、肾和子宫周围脂肪垫湿重、脂肪系数、血清瘦素和脂联素含量。结果:LGSG处理肥胖大鼠5周后,饮食量和体质量明显低于模型组大鼠,脂肪湿重和脂肪系数明显减少(P<0.05或0.01),其中高剂量LGSG还能明显降低肥胖大鼠的Lee's指数(P<0.05),但血清瘦素含量与模型组比较无明显变化,脂连素含量较模型组略有升高,但无明显统计学差异(P>0.05)。高剂量LGSG能显著增加大鼠的自主行为(P<0.05或0.01)。结论:LGSG对奥氮平诱导的肥胖大鼠有显著减肥作用,但其减肥作用可能与瘦素和脂联素的调节无关。     

胰岛素抵抗大鼠体内儿茶酚胺含量变化机制研究

目的：观察由高脂饲料诱导的胰岛素抵抗（IR）大鼠中枢与外周儿茶酚胺（CA）含量的变化并探讨其机制。方法：用空腹血糖、空腹血胰岛素、胰岛素敏感指数、IR指数等指标来评估IR动物模型的形成;用血清皮质酮反映IR形成过程中糖皮质激素的变化;用套尾法测量血压;用下丘脑、脑干、血清、肾上腺组织中多巴胺（DA）、肾上腺素（E）和去甲肾上腺素（NE）的变化来评价IR大鼠体内中枢与外周CA交感神经活性的变化。结果：高脂饲料喂养8周后大鼠出现IR并伴SBP升高,中枢与外周CA的含量明显升高（P〈0．01）;给予米非司酮和罗格列酮后血压明显改善,中枢与外周CA的含量明显下降（P〈0．05）。结论：高脂饲料诱发的IR状态大鼠中枢与外周CA的升高与血浆中糖皮质激素的改变有关。     

酮替芬对高糖高脂饮食诱导肥胖模型大鼠的减肥作用简

目的：探讨酮替芬对高糖高脂饮食诱导的大鼠肥胖模型的减肥作用及其机制。方法：SD大鼠随机分成肥胖模型组、酮替芬干预组和正常对照组,肥胖模型组和酮替芬干预组以高糖高脂饲料饲喂,正常对照组以基础饲料饲喂,酮替芬干预组每天灌胃给予酮替芬0．09mg／kg,持续12周。称重,计算Lee’s指数,检测空腹血糖（FBG）、空腹胰岛素（FINS）、瘦素（LEP）、游离脂肪酸（FFA）、甘油三酯（TG）、低密度脂蛋白胆固醇（LDL—C）、白介素-6（IL-6）、肿瘤坏死因子-α（TNF—α）;检测白色脂肪解偶联蛋白2（UCP2）mRNA的表达。结果：酮替芬明显降低肥胖模型大鼠的体质量及Lee’S指数（P〈0．05）,降低FBG、FINS和LEP水平（P〈0．05）,降低FFA、TG和LDL—C水平（P〈0．05）和IL-6、TNF—α水平（P〈0．05）,而增加UCP2mRNA的表达水平（P〈0．05）。结论：酮替芬能够降低肥胖模型大鼠炎症介质和游离脂肪酸水平,减轻高胰岛素血症和高瘦素血症,促进脂肪组织能量代谢,实现减肥作用。     

Localized effects of naloxone on local cerebral glucose utilization in rat cerebral nuclei with Met-enkephalinergic neurons

The alterations of local glucose utilization in 101 cerebral nuclei following the subcutaneous administration of the specific opioid antagonist naloxone were measured using the quantitative autoradiographic 14C-deoxy-D-glucose technique in conscious rats. Met5-enkephalin-like immunoreactivity (MELI) and ME receptor binding (MERB) levels in 82 cerebral nuclei were assayed quantitatively by microdensitometry of fluorescence micrographs and autoradiographs of the brain slices. Naloxone administration significantly reduced glucose utilization rate in 18 lower brainstem nuclei including the n. tractus solitarii, n. dorsalis nervi vagi, substantia grisea centralis, n. parabrachialis dorsalis and ventralis, and n. interpeduncularis. These nuclei contained ME perikarya with high levels of MELI and MERB. However, naloxone did not alter glucose utilization of other lower brainstem nuclei containing ME neurons and all thalamic, epithalamic, hypothalamic and limbic nuclei with ME perikarya. The distribution and magnitude of the neuronal response of cerebral nuclei to naloxone were apparently not related to the distributions of ME neurons. The present study offers direct evidence for the selective action of naloxone per se in some lower brainstem nuclei with ME perikarya.     

Pharmacological characterization of presynaptic alpha-adrenoceptors in the nucleus tractus solitarii and the cerebral cortex of the rat

The presynaptic alpha-adrenoceptors mediating inhibition of K+-induced release of [3H]noradrenaline (NA) from superfused slices and synaptosomes obtained from the nucleus tractus solitarii (NTS) region were characterized pharmacologically and compared to those in the cerebral cortex. Clonidine concentration-dependently (pD2 7.80) reduced the K+-induced [3H]NA release from slices and synaptosomes from the nucleus tractus solitarii of both normotensive and spontaneously hypertensive rats; 10(-6) M clonidine inhibited the [3H]NA release induced by 10 mM K+ to 40% of control. This inhibitory effect of clonidine was antagonized by the alpha2-adrenoceptor antagonist yohimbine (10(-7) M), but not by the alpha1-adrenoceptor antagonist prazosin (10(-7) M). The rank order of apparent affinities of agonists for the presynaptic alpha-adrenoceptors mediating inhibition of [3H]NA release from slices of nucleus tractus solitarii induced by 20 mM K+, was: oxymetazoline greater than clonidine greater than adrenaline greater than alpha-methylnoradrenaline greater than noradrenaline much greater than methoxamine. A similar rank order was found for cerebral cortex slices. The rank order of intrinsic activities in both brain regions was found to be: noradrenaline approximately equal to alpha-methylnoradrenaline approximately equal to adrenaline greater than clonidine greater than oxymetazoline much greater than methoxamine. The data indicate that presynaptic alpha-adrenoceptors mediating inhibition of NA release both in the nucleus tractus solitarii and the cerebral cortex belong to the alpha2-type. The presynaptic alpha2-adrenoceptors in the two brain regions appear to be similar both functionally and pharmacologically. It is suggested that these receptors in the nucleus tractus solitarii may play a role in the hypotensive effect of clonidine.     

Ethanol inhibition of stress-related tachycardia involves medullary NMDA receptors

In rats, neurons in the perifornical area of the hypothalamus send descending projections to the commissural part of the nucleus tractus solitarii as demonstrated by an anterograde tracer study. In urethane-anaesthetised rats, stimulation of neurons in the perifornical area by microinjection of bicuculline or 6-OH-saclofen causes tachycardia and inhibits baroreflex bradycardia. The effects elicited from the perifornical area are similar in magnitude to those elicited from the adjacent dorsomedial nucleus, also called the hypothalamic defense area. Microinjection into the nucleus tractus solitarii of the NMDA (N-methyl- -aspartate) receptor antagonist, AP-7 (2-amino-7-phosphonoheptanoic acid), inhibits the tachycardic response to stimulation of the perifornical area. Injection of ethanol intravenously or into the nucleus tractus solitarii also inhibits this tachycardic response, but causes no further inhibition when combined with AP-7. We conclude that the perifornical area is part of the hypothalamic defense area, and it is under strong, tonic GABAergic inhibition mediated by both GABA_A and GABA_B receptors. Furthermore, descending input from the perifornical area to the nucleus tractus solitarii is via an NMDA synapse, and ethanol inhibits stress-related tachycardia by inhibiting these NMDA receptors in the nucleus tractus solitarii.     

Catecholamine utilization in distinct mouse brain nuclei during acute morphine treatment, morphine tolerance and withdrawal syndrome

The steady-state levels and utilization (alpha-MPT-induced disappearance) of noradrenaline (NA) and dopamine (DA) were measured in distinct mouse brain nuclei after acute morphine challenge, in mice rendered tolerant to morphine, and during the naloxone-precipitated morphine withdrawal syndrome. Mouse brain nuclei containing mainly the cell body areas and some terminal projections of major NA- and DA-containing pathways were selected (nucleus tractus solitarii, locus coeruleus, substantia nigra, area tegmentalis ventralis and nucleus caudatus, nucleus accumbens, gyrus dentatus hippocampi, nucleus raphe dorsalis respectively). Acute morphine treatment reduced the utilization of NA in all brain nuclei but the substantia nigra. In morphine-tolerant mice, all changes characteristic for acute morphine treatment disappeared. Instead, an increased NA utilization was observed in the nucleus tractus solitarii and the area tegmentalis ventralis in the tolerant animals. During morphine withdrawal, an abrupt decrease was observed in the utilization of NA in the nucleus tractus solitarii, whereas the NA utilization in the gyrus dentatus abruptly increased, as compared to the tolerant state. Acute morphine challenge decreased the utilization of DA in the nucleus caudatus, locus coeruleus and nucleus raphe dorsalis. In the tolerant mouse, an increased utilization of DA was observed in the nucleus tractus solitarii. During morphine withdrawal, DA utilization was decreased in the substantia nigra and the area tegmentalis ventralis, while in the nucleus accumbens withdrawal resulted in an increase of DA utilization. The data suggest that acute effects of morphine as well as morphine tolerance/dependence are accompanied by, and likely to be associated with, distinct changes in the catecholamine metabolism of specific mouse brain nuclei.     

Reciprocal regulation of nitric oxide and glutamate in the nucleus tractus solitarii of rats

Nitric oxide (NO) and glutamate are both important mediators of the central cardiovascular regulation in the nucleus tractus solitarii. Our previous studies revealed that the central cardiovascular effects of NO in the nucleus tractus solitarii could be inhibited by glutamate receptor blockade. On the other hand, nitric oxide synthase (NOS) inhibitor attenuated the cardiovascular effects of glutamate. Thus, NO and glutamatergic systems appear to interact in central cardiovascular regulation. The present study examined whether NO and glutamate may affect each other's release/production in the nucleus tractus solitarii. A microdialysis probe was implanted into the nucleus tractus solitarii of male Sprague-Dawley rats, and the changes in the extracellular levels of glutamate and NO were determined by high performance liquid chromatography coupled with electrochemical detection and an NO analyzer, respectively. The results showed that NO solution elicited >10 fold increases in the extracellular level of glutamate, which returned to normal 60 min after the end of NO perfusion. The NO donor N-acetyl-penicillamine (SNAP) had an effect similar to NO solution. Furthermore, the glutamate level was reduced to 61% of basal value by perfusion with the NOS inhibitor, N(G)-monomethyl-L-arginine (L-NMMA). When glutamate receptor agonist N-methyl-D-aspartic acid (NMDA) or alpha-amino-3-hydroxy-5-methylixoxazole-4-propionic acid (AMPA) was administered into the nucleus tractus solitarii, the extracellular NO level was increased by 70-100%, whereas glutamate receptor antagonists (MK-801 hydrogen maleate and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX)) did not alter the basal levels of NO. These results suggest that NO and glutamate may enhance each other's release/production in the nucleus tractus solitarii. This reciprocal regulation of NO and glutamate may be important in central cardiovascular control in the nucleus tractus solitarii.     

The effect of moxonidine on feeding and body fat in obese Zucker rats: role of hypothalamic NPY neurones.

The antihypertensive agent moxonidine, an imidazoline Ii-receptor agonist, also induces hypophagia and lowers body weight in the obese spontaneously hypertensive rat, but the central mediation of this action and the neuronal pathways that moxonidine may interact with are not known. We studied whether moxonidine has anti-obesity effects in the genetically-obese and insulin-resistant fa/fa Zucker rat, and whether these are mediated through inhibition of the hypothalamic neuropeptide Y (NPY) neurones. Lean and obese Zucker rats were given moxonidine (3 mg kg(-1) day(-1)) or saline by gavage for 21 days. Moxonidine decreased food intake throughout by 20% in obese rats (P<0.001) and by 8% in lean rats (P<0.001), and reduced weight gain that final body weight was 15% lower in obese (P<0.001) and 7% lower in lean (P<0.01) rats than their untreated controls. Plasma insulin and leptin levels were decreased in moxonidine-treated obese rats (P<0.01 and P<0.05), but unchanged in treated lean rats. Uncoupling protein-1 gene expression in brown adipose tissue was stimulated by 40-50% (P< or =0.05) in both obese and lean animals given moxonidine. Obese animals given moxonidine showed a 37% reduction in hypothalamic NPY mRNA levels (P = 0.01), together with significantly increased NPY concentrations in the paraventricular nucleus (P<0.05), but no changes in the arcuate nucleus or other nuclei; this is consistent with reduced NPY synthesis in the arcuate nucleus and blocked release of NPY in the paraventricular nucleus. In lean animals, moxonidine did not affect NPY levels or NPY mRNA. The hypophagic, thermogenic and anti-obesity effects of moxonidine in obese Zucker rats may be partly due to inhibition of the NPY neurones, whose inappropriate overactivity may underlie obesity in this model.     

A cholecystokinin-1 receptor agonist (CCK-8) mediates increased permeability of brain barriers to leptin

BACKGROUND AND PURPOSE: Leptin regulates energy expenditure and body weight by acting both on the hypothalamus and on peripheral targets. Central actions of leptin are enhanced by cholecystokinin (CCK). The interaction between leptin and CCK makes physiological sense, as rats lacking CCK1 receptors are resistant to peripheral leptin but not to leptin directly infused into the brain. We have recently reported that CCK enhances leptin effects by increasing the entry of leptin into the CNS. The aim of this work was to further characterize the effect of CCK (10 microg kg(-1)) on leptin kinetics as well as the CCK receptor subtype involved in the interaction between CCK and leptin. EXPERIMENTAL APPROACH: Experiments were carried out both in free-feeding and in fasted rats receiving a single dose of leptin (100 microg kg(-1); i.p.). Parameters analysed over the next 6 h were plasma and cerebrospinal fluid concentrations of leptin. KEY RESULTS: We observed that CCK-8 depressed the increase in plasma leptin that followed the i.p. injection and simultaneously increased leptin concentration in the cerebrospinal fluid from 92+/-25 to 230+/-24 pg mL(-1) (P<0.05). The effect of CCK-8 was totally prevented by the CCK1 receptor antagonist, SR-27,897 (0.3 mg kg(-1), s.c.), but not by the CCK2 receptor antagonist, L-365,260 (1 mg kg(-1)). CONCLUSIONS AND IMPLICATIONS: These results show that CCK plays a role in regulating the access of leptin to the brain and suggest that CCK analogues, acting on CCK1 receptors, might be useful drugs in improving leptin actions within the brain.     

Weight loss and hypophagia after high-dose AT1-blockade is only observed after high dosing and depends on regular leptin signalling but not blood pressure

AT₁-blockade has been shown to induce weight loss in animals or patients. The aim of this study was to investigate whether weight reduction after AT₁-blockade is dependent on dose, blood pressure reduction and leptin signalling. Spontaneously hypertensive rats (SHR) and lean and obese Zucker rats were treated for 4?weeks with candesartan (0, 2, 6 or 16?mg/kg/day). Body weight, food intake and hypothalamic mRNA levels of (an)orexigenic peptides were determined. Obese Zucker rats served as a model of primary leptin resistance. In SHR, body mass index and food intake were decreased selectively by 16?mg/kg/day candesartan but not after using normal (2?mg/kg/day) or supranormal (6?mg/kg/day) doses. Correlation analysis between blood pressure and body weight indicated no relationship of hypotensive potency on weight loss. The hypothalamic mRNA levels of the orexigenic peptide MCH (melanin-concentrating hormone) were diminished in parallel. Consistent to the results in SHRs, 16?mg/kg/day candesartan revealed a decrease of body weight, food intake and hypothalamic MCH mRNA levels in lean Zucker rats. In obese Zucker rats, none of these parameters were reduced by candesartan. Loss of body weight and hypophagia are not general features of AT₁-blockers, since neither was seen after normal or moderately supranormal doses, but they were, after the highest doses. These actions of AT₁-blockers occur independently of their ability to lower blood pressure. They do depend on an intact leptin signalling, since they were absent in obese Zucker rats that feature a genetic mutation of the leptin receptor.     

L-3,4-dihydroxyphenylalanine-induced c-Fos expression in the CNS under inhibition of central aromatic L-amino acid decarboxylase

L-3,4-dihydroxyphenylalanine (DOPA) is a neurotransmitter candidate. To map the DOPAergic system functionally, DOPA-induced c-Fos expression was detected under inhibition of central aromatic L-amino acid decarboxylase (AADC). In rats treated with a central AADC inhibitor, DOPA significantly increased the number of c-Fos-positive nuclei in the paraventricular nuclei (PVN) and the nucleus tractus solitarii (NTS), and showed a tendency to increase in the supraoptic nuclei (SON), but not in the striatum. On the other hand, DOPA with a peripheral AADC inhibitor elevated the level of c-Fos-positive nuclei in the four regions, suggesting that DOPA itself induces c-Fos expression in the SON, PVN and NTS. In rats treated with 6-hydroxydopamine (6-OHDA) to lesion the nigrostriatal dopamine (DA) pathway, DOPA significantly induced c-Fos expression in the four regions under the inhibition of peripheral AADC. However, under the inhibition of central AADC, DOPA did not significantly increase the number of c-Fos-positive nuclei in the four regions, suggesting that DOPA at least in part induces c-Fos expression through its conversion to DA. It was likely that the 6-OHDA lesion enhanced the response to DA, but attenuated that to DOPA itself. In conclusion, we proposed that the SON, PVN and NTS include target sites for DOPA itself.     

The association of serum leptin with the reduction of food intake and body weight during electroacupuncture in rats

Previous studies indicate that acupuncture or electroacupuncture (EA) treatment reduces body weight and food intake in rats by increasing the level of anoretic peptides and decreasing that of orexigenic peptides in the hypothalamus. Considering a well-established role of leptin as a major regulator for feeding behavior in the hypothalamus, we hypothesized that EA might exert its effect via increasing serum leptin levels. In this study, we tested our hypothesis by evaluating the effects of EA on food intake and body weight, as well as on serum leptin levels in rats. Rats were randomly divided into 3 groups: AL (fed ad libitum with no treatments), Holder (fed ad libitum with daily holder restraint) and EA (fed ad libitum with daily holder restraint and 100 Hz EA stimulation) groups. During the four-week experimental period, daily food intake and body weight were measured. At the end of the experiment, levels of serum leptin and corticosterone, and plasma epinephrine (Epi) and norepinephrine (NE) were determined. Here we demonstrate that EA treatment indeed led to reduction of food intake and body weight, and to an increase of serum leptin levels. The level of Epi, NE, and corticosterone increased in the Holder group, but such increase in the level of aforementioned stress hormones was not observed in the EA group. Overall, our results suggest that EA treatment reduces food intake and body weight in rats possibly through increasing leptin levels, and that this effect of EA is not due to the stress caused by the daily holder restraint.