低氧运动干预肥胖模型大鼠下丘脑Nesfatin-1和Ghrelin水平

文题释义：Ghrelin：是一种含有28个氨基酸残基的短肽，于1999年被发现，主要由胃底分泌，在下丘脑中也有表达，其可促进摄食、减少能量消耗和增加体质量，是目前发现的唯一促食欲激素。 Nesfatin-1：是一种由82个氨基酸组成的神经肽，于2006年被发现，具有减少摄食、调节能量平衡和减轻体质量的作用。 背景：均衡饮食和科学运动是公认的安全、有效且经济的体质量管理干预方式，但运动本身有时却提升了减肥者食欲，如果将低氧环境刺激和有氧运动干预结合，可能会收到最好的减质量效果。下丘脑作为机体调控摄食和能量平衡的中枢，其调控因子与肥胖症发病机制之间的关系备受关注。 目的：观察低氧或/和运动后肥胖大鼠下丘脑nesfatin-1和ghrelin水平变化，探讨低氧或/和运动影响机体摄食和体质量的神经内分泌机制。 方法：60只营养性肥胖SD大鼠均分为常氧安静组、常氧运动组、16.3%低氧安静组、16.3%低氧运动组、13.3%低氧安静组和13.3%低氧运动组，进行8周的低氧或/和运动干预。低氧环境采用低氧发生器分别营造体积分数为16.3%氧气和13.3%氧气环境，低氧干预组大鼠每天12 h在低氧环境中生活和运动；运动干预采用跑台运动方案(跑速20 m/min、坡度0°)，持续时间40 min，5 d/周。记录干预期大鼠体质量、摄食量，计算干预前后Lee’s指数，用ELISA试剂盒检测干预后大鼠下丘脑nesfatin-1和ghrelin水平。 结果与结论：①干预后大鼠体质量与Lee’s指数：单纯低氧环境刺激对大鼠体质量、Lee’s指数的影响没有单纯有氧运动刺激明显，而当低氧和运动结合时，其效果优于单一刺激；②干预期间大鼠日均摄食量：常氧安静组保持平稳，其余各组均减少，尤以16.3%低氧运动组、13.3%低氧运动组明显；③下丘脑nesfatin-1和ghrelin水平：低氧结合运动可影响大鼠下丘脑nesfatin-1水平，其中13.3%低氧运动组的nesfatin-1水平最高；单纯的运动或低氧均可影响大鼠下丘脑ghrelin水平，而单一运动刺激效果强于单一低氧刺激，当二者结合时降低效果更明显；④双因素方差分析：体质量和ghrelin水平受运动的影响，体质量、Lee’s指数和摄食量受氧气体积分数的影响，体质量、nesfatin-1和ghrelin水平受运动×氧气体积分数的影响；⑤结果表明，8周低氧运动可能通过影响肥胖大鼠下丘脑nesfatin-1与ghrelin水平来减少大鼠的摄食量，抑制其体质量增长，降低其Lee’s指数，但具体机制需待进一步研究。 ORCID: 0000-0002-1519-7825(范锦勤) 中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程     

α—MSH抑制内毒素知症大鼠不同组织表达巨噬细胞移动抑制因子mRNA

目的 研究α－黑素细胞刺激素（α-MSH)对内毒素血症大鼠不同组织表达炎症反应介质巨噬细胞移动抑制因子（MIF）的影响，以探讨α-MSH的抗炎作用机理。方法 SD大鼠腹腔注射LPS建立内毒素血症动物模型，静脉给予α-MSH处理，采用半定量RT－PCR和northern印迹杂交的方法，检测大鼠不同组织MIF mRNA的表达。结果 内毒素血症大鼠垂体、下丘脑、海马、大脑皮层及肾上腺和脾脏MIF mRNA的表达与正常大鼠比较明显增强，α－MSH对大鼠垂体、海马、肾上腺和脾脏MIF mRNA的表达具有明显的抑制作用，但对大脑皮层和下丘脑部位MIF mRNA的表达无明显影响。结论 α－MSH能抑制中枢神经系统和外周器官表达MIF可能在其抗全身炎症反应中起重要作用。     

下丘脑室旁核外源性orexin-A对肥胖大鼠摄食的影响及NPY受体信号的调控

目的:探讨饮食诱导肥胖(DIO)大鼠神经肽Y(NPY)受体信号通路是否参与下丘脑室旁核(PVN)外源性注射食欲素A(orexin-A)对摄食和葡萄糖敏感(GS)神经元兴奋性的调控。方法:采用荧光免疫组织化学实验观察PVN中orexin-A受体(即食欲素1型受体,OX1R)和NPY受体Y5(NPY-5R)的表达;采用单细胞外放电记录观察orexin-A对PVN内GS神经元兴奋性的影响;分别于SD大鼠和DIO大鼠PVN埋置套管,经套管注射orexinA、OX1R拮抗剂SB-334867和NPY-5R拮抗剂CGP-71683,观察大鼠0~2 h和0~4 h摄食量。结果:DIO大鼠PVN中OX1R和NPY-5R的表达显著高于SD大鼠。Orexin-A抑制PVN内葡萄糖抑制性(GI)神经元,兴奋葡萄糖兴奋性(GE)神经元,但是orexin-A对GS神经元的兴奋或抑制效应可被NPY-5R拮抗剂CGP-71683部分阻断,且与SD大鼠相比,orexin-A对DIO大鼠PVN内GS神经元兴奋或抑制效应更加明显。PVN内注射orexin-A可增加SD大鼠和DIO大鼠摄食量。但是orexin-A诱导的促摄食效应被NPY-5R拮抗剂CGP-71683部分阻断。与SD大鼠相比,orexin-A诱导的促摄食效应在DIO大鼠中更加明显。结论:PVN内外源性注射orexin-A可能主要通过OX1R信号通路参与大鼠摄食和GS神经元兴奋性调控,NPY-5R信号也参与了该过程调控,在DIO大鼠中更敏感。     

Ghrelin对脑缺血再灌注大鼠脑水肿和水通道蛋白4表达的影响

 目的： 探讨ghrelin对脑缺血再灌注大鼠脑水肿、血脑屏障通透性及水通道蛋白4（AQP4）表达的影响。方法： 成年SD雄性大鼠随机分为3组:sham组、大脑中动脉阻塞（MCAO）组和ghrelin处理组。采用线栓法复制MCAO模型（缺血2 h,再灌注22 h）。Ghrelin组大鼠于再灌开始时经股静脉注射ghrelin 10 nmol/kg。TTC染色观察脑梗死体积,神经功能评分判断脑功能障碍程度,分别以体积计算和干湿重法检测脑肿胀程度和脑含水量的变化,收集脑血管外伊文思蓝(EB)来评估血脑屏障的破坏程度,免疫组化和Western blotting检测AQP4的表达变化。结果： 与MCAO组比较,ghrelin处理组的脑梗死体积较小（P<0.01）,神经功能评分较低（P<0.01）,脑组织中的EB渗出量较少（P<0.01）。Ghrelin处理组大鼠的脑肿胀体积、脑含水量和AQP4表达明显低于MCAO组（P<0.05）。结论： Ghrelin减轻大鼠脑缺血/再灌注损伤,减轻脑水肿和血脑屏障的破坏,抑制脑组织中AQP4的表达。AQP4在ghrelin的脑保护机制中可能发挥重要作用。     

奥沙利铂对大鼠下丘脑及外周血中Ghrelin表达的影响

目的:研究化疗药物奥沙利铂对大鼠下丘脑中神经肽Ghrelin表达水平的影响。方法:SD大鼠分为对照组和奥沙利铂处理组,观察各组大鼠摄食量变化。real-time RT-PCR检测各组大鼠下丘脑中Ghrelin mRNA表达变化,免疫组化和Western Blot方法检测大鼠下丘脑中Ghrelin蛋白的表达水平。结果:奥沙利铂化疗后,大鼠第2～4 d摄食量减少。奥沙利铂化疗后大鼠血浆酰化Ghrelin浓度显著下降。化疗后第3 d大鼠血浆酰化ghrelin为52. 5±2. 1 pmol/l,显著低于NS对照组86. 5±4. 7 pmol/l(P 0. 05)。奥沙利铂化疗后大鼠下丘脑内Ghrelin mRNA及蛋白表达水平在第1、3 d和5 d均下降,其中第3 d下降最显著。结论:奥沙利铂化疗可降低大鼠食欲,降低Ghrelin在下丘脑中的表达。     

下丘脑室旁核CRH神经元激活在慢性充血性心力衰竭中的交感兴奋作用

目的:观察慢性心衰时下丘脑室旁核(PVN)内促肾上腺皮质激素释放激素(CRH)表达变化及其与交感神经活动之间的关系。方法:健康雄性SD大鼠,冠脉结扎制备心衰模型,侧脑室插管渗透压泵持续给药。假手术组和心衰组给予人工脑脊液0.25μL/h,心衰给药组给予CRH抑制剂αh-CRH 15 mg/h。同时,选取健康雄性体内CRH合成不足的Lewis大鼠与同源纯种Fischer 344大鼠分别制备心衰模型和假手术对照进行对比研究。4周后,测定左室舒张末压(LVEDP)、左室内压最大上升和下降速率(±dp/dtmax)、右心室/体重比(RV/BW)、肺/体重比(lung/BW)、肾交感神经放电活动(RSNA)、血浆去甲肾上腺素(NE)浓度和PVN内CRH阳性神经元数目。血浆促肾上腺皮质激素(ACTH)含量。结果:与假手术组相比,SD心衰大鼠PVN内CRH阳性神经元数目明显增加,血浆ACTH浓度升高,RSNA增强,血浆NE浓度增加,LVEDP、lung/BW和RV/BW增加,±dp/dtmax降低;心衰模型后给予αh-CRH可明显逆转上述各种变化(P0.05)。Fisher 344大鼠心衰组和假手术对照相比,PVN内CRH阳性神经元数目明显增加,血浆ACTH浓度升高,RSNA增强,外周血NE浓度升高,LVEDP、RV/BW和lung/BW增加,±dp/dtmax下降(P0.05)。但Lewis大鼠心衰组和假手术对照相比,以上各指标改变均不明显。结论:慢性心衰时,下丘脑室旁核CRH神经元被激活,激活的CRH神经元可增强外周交感神经活动,加重心功能恶化。     

不同游泳训练方式对大鼠下丘脑室旁核c-fos表达的影响

为了观察游泳运动后大鼠下丘脑室旁核(PVN)内c-fos mRNA及Fos免疫阳性神经元的表达变化,探讨下丘脑PVN对不同形式运动的调节机制,本实验将60只雄性SD大鼠随机分为对照组(n=10)和运动组(n=50),建立大鼠游泳运动模型(持续训练和间歇训练)。在运动结束后0、0.5、1、2、4h等不同时间点,冰水浴分离新鲜脑组织或用多聚甲醛灌注固定取脑,前者经RT-PCR反应,半定量分析运动后下丘脑PVN内c-fos mRNA的含量变化,后者经冰冻切片、免疫组织化学染色,观察Fos免疫阳性神经元的定位和分布情况。结果显示:(1)对照组大鼠下丘脑PVN内c-fos mRNA表达极低,而运动结束后c-fos mRNA表达明显升高。持续运动组逐渐升高,1h时达到最大值;间歇训练结束后2h,c-fos mRNA表达最强,然后回落,运动结束4h组c-fos mRNA仍较对照组显著增多(P<0.05);(2)运动大鼠Fos免疫阳性神经元的数目明显增多,特别是在PVN处。在室旁核小细胞部(pPVN),持续组游泳结束后1hFos阳性神经元的数目显著升高达峰值,而间歇组在运动结束后2h达峰值,同一时刻间歇组的表达高于持续运动组;室旁核大细胞部(mPVN)内,持续组Fos阳性神经元数在运动结束后持续升高,2h后显著下降,而间歇组各时刻阳性神经元的表达变化无统计学差异(P>0.05)。以上结果提示,下丘脑PVN在运动后机体调节中起重要作用,不同的运动方式可以产生不同的影响,且pPVN对不同形式运动性应激反应具有较高灵敏度。     

孤束核参与室旁核加压素能神经元对大鼠胃缺血-再灌注损伤的调控作用

目的：探讨孤束核（NTS）在下丘脑室旁核（PVN）加压素能神经元对大鼠胃缺血-再灌注损伤（GI-RI）调控中的作用。方法：复制夹闭大鼠腹腔动脉30 min，松开动脉夹血流复灌1 h的GI-RI模型，观察核团内微量注射、电刺激、损毁等对其影响。结果：PVN内注射精氨酸加压素（AVP）能明显减轻GI-RI，且具有剂量-效应依赖关系（r=-0.477, P<0.05）；损毁双侧NTS或NTS内给予AVP受体阻断剂均能取消电刺激PVN对GI-RI的减轻作用；NTS内注射AVP的作用与PVN内注射AVP的效应相似。结论：NTS参与下丘脑室旁核加压素神经元对大鼠胃缺血-再灌注损伤的调控作用，并且是通过其中的AVP受体来实现的。     

CCK—8对内毒素休克大鼠肺泡巨噬细胞吞噬及p38MAPK 表达的影响

目的研究八肽胆囊收缩素(CCK-8)对脂多糖(LPS)引起的内毒素性休克(ES)大鼠脾脏和肺脏的TNF-α基因表达的影响,进一步探讨CCK-8的受体作用机制.方法尾静脉注入LPS(8mg/kgiv)复制大鼠ES模型、LPS注入前10min尾静脉注入CCK-8(40μg/kgiv)、单独注入CCK-8(40μg/kgiv)或生理盐水(对照)的四组大鼠分别于LPS注入后30min、2h和6h取脾脏和肺脏进行RT-PCR检测TNF-αmRNA表达.LPS注入后2h、6h和12h取脾脏进行RT-PCR检测CCKA/B受体mRNA表达.结果CCK-8可抑制LPS注入后30min和2h引起的脾脏和肺脏TNF-αmRNA表达的上调,注入LPS后6hTNF-αmRNA的表达与对照组比较没有显著差异.LPS注入后2h、6h和12hES大鼠脾脏CCK-8受体表达较对照组上调,以2h上调作用最为显著.讨论和结论TNF-α是一个早期的重要炎症介质,由于TNF-α能促进IL-1和IL-6等炎症介质的产生,而引起级链式的炎症反应,引起持续损害,LPS组6h尽管TNF-α下降,但病理损害仍比2h明显加重.我室以往研究已证实CCK-8有抗ES的作用.脾脏和肺脏是产生TNF-α的重要器官,CCK-8能抑制TNF-α的产生,可能通过抑制其转录而起作用.LPS诱导脾脏CCK受体表达增加,属疾病状态下的受体、配体间的正向调节.LPS致机体损伤的同时也启动了机体的保护机制,CCKA/B受体表达增加,是该保护机制之一.这些发现提示CCK-8逆转ES可能与其抑制TNF-α基因表达的作用有关;LPS可上调脾脏CCKA/B受体表达,说明CCK-8保护作用的受体机制.     

Ghrelin及其与肥胖和2型糖尿病的关系

Ghrelin是生长激素促泌物受体的第一个内源性配体。具有促进生长激素分泌、促进摄食、参与能量代谢等多种作用。对 ghrelin的深入研究 ,有望为肥胖和 2型糖尿病诊断和治疗开辟一条新途径。     

PVN-hindbrain pathway involved in the hypothalamic hyperphagia-obesity syndrome

This study examined the involvement of caudal brainstem projections of the hypothalamic paraventricular nucleus (PVN) in the medial hypothalamic (MH) hyperphagia-obesity syndrome. Experiment 1 demonstrated that a unilateral parasagittal knife cut in the MH combined with a contralateral coronal knife cut in either the ventrolateral pons (vP) or ventrolateral medulla (vM) significantly increased food intake and body weight in adult female rats. Overeating and overweight were also produced by a unilateral MH knife cut combined with a contralateral oblique cut under the nucleus of the solitary tract and dorsal motor nucleus of the vagus complex (NST/DX). In contrast, an MH cut x dorsolateral medullary cut combination did not increase food intake or body weight compared to a MH cut alone or sham surgery. Experiment 2 demonstrated that the hyperphagia/obesity effect of MH x vP knife cuts was comparable to that obtained with bilateral PVN lesions, but less than that produced by bilateral MH knife cuts. Bilateral vP cuts also increased body weight but the effect was less than that obtained with the other experimental treatments. Feeding the rats a high-fat diet rather than chow potentiated the hyperphagia and obesity syndromes produced by the various lesion conditions. Taken together, these findings suggest that the medial hypothalamic hyperphagia and obesity syndrome is due, in part, to damage to PVN projections to the caudal brainstem, the NST/DX complex in particular. The functional significance of this PVN-hindbrain "feeding" pathway and the identity of extra-PVN components of the hyperphagia-obesity syndrome remain to be established.     

Paraventricular nucleus lesions in weanling female rats result in normophagia, normal body weight and composition, linear growth and normal levels of several plasma substrates

Female weanling rats received small (1 mAmp for 5 sec) electrolytic lesions in the paraventricular nuclei. Sham-operated rats served as controls. The rats were maintained for 42 days and body weight, linear growth, Lee Index, food intake and efficiency of food utilization were determined throughout the study. Plasma glucose, glycerol, free fatty acids, total protein and carcass fat and protein were determined at sacrifice. There was no significant difference between the lesioned and the sham-operated rats in any of the parameters measured. The findings are interpreted to mean that the PVN of the weanling rat is not functionally mature or alternatively, that there exists a sex difference in weanling rats in response to PVN lesions.     

The rise, fall, and resurrection of the ventromedial hypothalamus in the regulation of feeding behavior and body weight

Early researchers found that lesions of the ventromedial hypothalamus (VMH) resulted in hyperphagia and obesity in a variety of species including humans, which led them to designate the VMH as the brain's "satiety center." Many researchers later dismissed a role for the VMH in feeding behavior when Gold claimed that lesions restricted to the VMH did not result in overeating and that obesity was observed only with lesions or knife cuts that extended beyond the borders of the VMH and damaged or severed the ventral noradrenergic bundle (VNAB) or paraventricular nucleus (PVN). However, anatomical studies done both before and after Gold's study did not replicate his results with lesions, and in nearly every published direct comparison of VMH lesions vs. PVN or VNAB lesions, the group with VMH lesions ate substantially more food and gained twice as much weight. Several other important differences have also been found between VMH and both PVN and VNAB lesion-induced obesity. Concerns regarding (a) motivation to work for food and (b) the effects of nonirritative lesions have also been addressed and answered in many studies. Lesion studies with weanling rats and adult pair-tube-fed rats, as well as recent studies of knockout mice deficient in the orphan nuclear receptor steroidogenic factor 1, indicate that VMH lesion-induced obesity is in large part a metabolic obesity (due to autonomic nervous system disorders) independent of hyperphagia. However, there is ample evidence that the VMH also plays a primary role in feeding behavior. Neuroimaging studies in humans have shown a marked increase in activity in the area of the VMH during feeding. The VMH has a large population of glucoresponsive neurons that dynamically respond to blood glucose levels and numerous histamine, dopamine, serotonin, and GABA neurons that respond to feeding-related stimuli. Recent studies have implicated melanocortins in the VMH regulation of feeding behavior: food intake decreases when arcuate nucleus pro-opiomelanocortin (POMC) neurons activate VMH brain-derived neurotrophic factor (BDNF) neurons. Moderate hyperphagia and obesity have also been observed in female rats with damage to the efferent projections from the posterodorsal amygdala to the VMH. Hypothalamic obesity can result from damage to either the POMC or BDNF neurons. The concept of hypothalamic feeding and satiety centers is outdated and unnecessary, and progress in understanding hypothalamic mechanisms of feeding behavior will be achieved only by appreciating the different types of neural and blood-borne information received by the various nuclei, and then attempting to determine how this information is integrated to obtain a balance between energy intake and energy output.     

Comparison of radio-frequency and electrolytic lesions of the paraventricular hypothalamic nucleus

Radio-frequency and anodal electrolytic lesions of the paraventricular nucleus (PVN) were found to produce equal and dramatic increases in body weight in female rats. Neither of the groups with lesions had significantly elevated plasma insulin levels during a period of food restriction, but individual values varied greatly. Both groups displayed marked basal hyperinsulinemia after 30 days of food ad lib. It is concluded that radio-frequency and electrolytic PVN lesions produce similar obesity syndromes.     

The effect of cholecystokinin-octapeptide on food intake and consummatory behavior in lactating rats.

Rats are less sensitive to the satiating effect of CCK-8 during some reproductive states such as estrus and proestrus, and in ovariectomized rats following the administration of estradiol and progesterone. The sensitivity of rats to CCK-8's effect on food intake decreases as lactation progresses. During lactation, prolactin and progesterone levels are elevated. Implantation of ectopic pituitaries increases prolactin levels in males and females as well as progesterone levels in females. To evaluate whether or not prolactin elevation modifies CCK's effect on feeding, we studied the effect of CCK-8 on food intake during the early dark cycle in male and female rats implanted with ectopic pituitaries. As previously demonstrated, prolactin levels were elevated in both male and female pituitary-implanted rats and progesterone levels were elevated in the female rats. CCK-8 inhibited food intake in sham-operated male rats, but did not reliably decrease early dark cycle food intake in sham-operated or pituitary-implanted female rats or pituitary-implanted male rats. Thus an elevation in prolactin levels does not appear to modify the effect of CCK-8 on food intake in female rats. We also evaluated the effect of CCK on consummatory and maternal behavior in lactating rats. CCK-8 altered the meal patterns of lactating rats primarily by decreasing the rate of food consumption and increasing the latency to the first meal. The latency to the first meal of rats receiving CCK was increased during early and mid-lactation and the PW period, but not during late lactation compared to that of the saline-injected rats. CCK-8 did not modulate any of the maternal behaviors studied.(ABSTRACT TRUNCATED AT 250 WORDS)     

Feeding studies in weanling rats with dorsomedial hypothalamic lesions: maintenance of competence to compensate for additional calories.

Weanling rats received bilateral electrolytic lesions in the dorsomedial hypothalamus primarily destroying the dorsomedial hypothalamic nuclei (DMN). Sham-operated rats served as controls. After a 14 day postoperative period during which food intake (lab chow) and body weight were recorded, each of the above groups were subdivided into 2 groups. One DMN group and one sham-operated control group were continued on lab chow alone throughout the remainder of the study. The other DMN group and the second control group were given additional calories in the form of a liquid diet by stomach tube during 2 separate periods of 10 and 14 days, respectivly, to increase their caloric intake beyond that taken in spontaneously. Both tube-fed groups reduced their ad lib caloric intake from chow considerably and to the same extent. Body weight gains were similar in tube-fed versus non-tube-fed rats, whether with or without DMN lesions. After the second, 14-day-long tube feeding period, however, DMN rats regulated their body weight somewhat less precisely than the controls. This may be related to their reduced food intake during that time period. The data indicate that weanling rats with DMN lesions, despite their basic hypophagia, do not show a deficit in caloric metering and gross body weight regulation.     

Opiates and medial hypothalamic knife cuts cause hyperphagia through different mechanisms

Several experiments were performed to determine whether the hyperphagia caused by medial hypothalamic knife cuts and that induced by opiate agonists are mediated by a common mechanism. In the first set of experiments, male Sprague-Dawley rats were given bilateral parasagittal medial hypothalamic knife cuts or a sham procedure and fed a high-fat Crisco-chow diet. Knife-cut and sham-operated rats were approximately equally sensitive to the suppressive effects of naloxone on food intake. The kappa opiate receptor agonist ketocyclazocine generally increased daytime food intake in sham-operated rats; in contrast, the normal hyperphagia of knife-cut rats was in most cases either unchanged or decreased by ketocyclazocine. In a second set of experiments, neither diet composition nor hypothalamic knife cuts significantly affected the feeding responses to naloxone or the stimulatory effects of the kappa agonist butorphanol tartrate. It was hypothesized that the differential effects of ketocyclazocine in knife-cut and sham-operated rats are a consequence of the sedative effects of the drug combined with the elevated baseline of the knife-cut subjects. This hypothesis was supported by a third experiment, in which ketocyclazocine also reduced nocturnal intake in unoperated rats and butorphanol increased intake. That feeding responses to naloxone and butorphanol were essentially unchanged by hypothalamic knife cuts suggests that the opioid feeding system is independent of the longitudinal feeding inhibitory pathway believed to be involved in knife-cut-induced hyperphagia.     

Cingulate lesions and behavioral adaptation to amino acid imbalanced diets

The effect of anterior cingulate cortex lesions on dietary intake and adaptation of disproportionate amounts of amino acids was examined. Rats with bilateral electrolytic lesions in the anterior cingulate cortex and sham-operated rats were fed, in turn, amino acid basal, imbalanced or devoid diets involving threonine and isoleucine as the growth limiting amino acids, and then a low protein (6% casein) followed by a high protein (75% casein) diet. Lesions of the anterior cingulate cortex did not prevent the initial depression in food intake of the amino acid imbalanced diets, but shortened the duration of anorexia associated with dietary amino acid imbalances. Cingulate lesions did not influence the food intake of rats fed amino acid devoid diets. When switched from a low protein to a high protein diet, animals bearing lesions and sham-operated controls reduced markedly their initial food intake and adapted to the high protein diet in similar manner. It was concluded that the initial food intake depression associated with a dietary amino acid imbalance is a direct response to postingestive cues which influence food intake. Moreover, that the difference in adaptive intakes of the cingulate cortex lesioned animals who ingested a diet of imbalanced amino acids or of high protein, indicates that separate mechanisms act to control food intake of animals fed diets containing imbalanced amino acid mixtures or diets with excessive amounts of protein.     

Changes in brain met-enkephalin concentrations with peripheral CCK injections in Zucker rats

There is increasing evidence that peptides in the brain are important in the control of food intake. Administration of opioid and CCK peptides have elicited hunger and satiety, respectively. To evaluate the interaction of these peptides and their role in the central nervous system, concentrations of met-enkephalin were measured in the hypothalamus of rats following peripheral administration of CCK; in addition, effects of feeding and fasting and obesity were studied. In CCK- vs. saline-injected rats met-enkephalin concentrations were decreased in the paraventricular nucleus (PVN), suprachiasmatic nucleus (SC), supraoptic nucleus (SON), dorsomedial hypothalamus (DMH) and ventromedial hypothalamus (VMH). In fed compared with fasted rats met-enkephalin concentrations were higher in the anterior hypothalamus (AH) and lower in the SC; in obese compared with lean rats, concentrations were higher in the AH, PVN, SC, SON, DMH, lateral hypothalamus and VMH. These results show that peripheral injections of CCK can decrease concentrations of met-enkephalin in the brain and suggest a mechanism by which these peptides may interact to influence behavior. In addition, the findings support the hypothesis that the hyperphagia which is typical of obese rats may be due to increased concentrations of met-enkephalin.     

Lateral hypothalamic lesions and fenfluramine increase thermogenesis in brown adipose tissue

The effects of treatment with fenfluramine or electrolytic lesions in the lateral hypothalamus (LH) on binding of guanosine 5-diphosphate (GDP) by mitochondria from brown adipose tissue have been compared in 4 experiments. In 2 experiments the lesions were lateral to the anterior hypothalamic nucleus and in the other two they were lateral to the ventromedial hypothalamic nucleus. Binding of GDP to mitochondria was significantly increased 18 hours after an electrolytic lesion in either LH site. d,1-Fenfluramine, 20 mg/kg, also increased GDP binding in both acute experiments. In the other 2 experiments GDP binding was measured 11 days after the LH lesion or after 11 daily injections of fenfluramine. When the chronic lesions were lateral to the VMN, there was a transient drop in food intake and body weight. With more anterior lesions, body weight remained significantly lower than in sham-operated rats although food intake returned slowly to control levels. Fenfluramine-treated rats had lower body weights in both chronic experiments even after food intake returned to normal. GDP-binding to mitochondria from interscapular brown adipose tissue was elevated in both of the chronically-treated fenfluramine groups but was only increased in the LH-lesioned rats whose body weight remained below normal.