Novel modulators for body weight changes induced by fasting and re-feeding in mice

Catch-up weight gain after malnutrition is a risk factor for metabolic syndrome. Here we show that social isolation enhanced fasting-induced weight loss and suppressed weight gain induced by re-feeding for 6 days following a 24-h fast in prepubertal wild-type mice. These effects of social isolation on weight gain were not associated with significant changes in daily average food consumption. Under the same housing condition, genetic deletion of β-endorphin reduced the fasting-induced weight loss and enhanced the re-feeding-induced weight gain in prepubertal mice. These effects of social isolation or genetic deletion of β-endorphin on these weight changes were attenuated and reversed in postpubertal mice. Moreover, genetic deletion of β-endorphin attenuated these effects of social isolation on the catch-up weight gain in prepubertal mice and reversed them in postpubertal mice. Thus, social isolation, endogenous β-endorphin, and age can be novel modulators for body weight changes induced by fasting and re-feeding in mice.     

中华蟾蜍体重及脏器大小对禁食和重喂食处理的响应

两栖动物的体重和内脏器官大小可随环境条件而变化,具有表型可塑性,但实验例证较少,尤其缺乏与可变的食物可利用性有关的研究。本研究以捕自安徽省定远县县郊的雌、雄中华蟾蜍(Bufo gargarizans)为研究对象,测定了自由取食组、禁食1周组、禁食2周组、重喂食1周组和重喂食2周组其体重、内脏器官湿重和干重的变化情况。1)中华蟾蜍的体重、胴体湿重和干重均无明显的性别(P0.05)和组间(P0.05)差异。2)雌蟾胃的湿重、干重和大肠湿重高于雄蟾(P0.05),其他内脏器官(小肠、胸腺、心、肝、肺、脂肪体、脾和肾)的湿重和干重均无性别差异(P0.05);雄蟾上述指标均无组间差异(P0.05);雌蟾的胃湿重和大肠湿重均无组间差异(P0.05),但胃干重自由取食组高于重喂食1周组(P0.05)。禁食2周组的小肠湿重下降,低于自由取食组、重喂食1周和2周组(P0.05)。3)禁食1周组的心湿重高于重喂食2周组(P0.05)。结果表明,中华蟾蜍在整体水平不受短期禁食和重喂食处理的影响,器官水平可能主要依赖适度饥饿而导致的心肌功能的提升和消化道的可塑性来应对变化的食物条件。     

In vivo differential effects of fasting, re-feeding, insulin and insulin stimulation time course on insulin signaling pathway components in peripheral tissues

Background: Components of the insulin receptor signaling pathway are probably some of the best studied ones. Even though methods for studying these components are well established, the in vivo effects of different fasting regimens, and the time course of insulin receptor phosphorylation and that of its downstream components in insulin-sensitive peripheral tissues have not been analyzed in detail. Rationale: When assessing insulin signaling, it may be beneficial to drive insulin levels as low as possible by performing an overnight fast before injecting a supra-physiological dose of insulin. Recent studies have shown however that 5 or 6 h fast in mice is sufficient to assess physiological responses to insulin and/or glucose in glucose tolerance tests [1], insulin tolerance tests [2], [3] and [4] and euglycemic hyperinsulinemic clamp studies [5] and [6]. Moreover, mice are nocturnal feeders, with ∼70% of their daily caloric intake occurring during the dark cycle [5], and their metabolic rate is much higher than humans. Therefore, an overnight fast in mice is closer to starvation than just food withdrawal. Thus our aim was to assess insulin signaling components from the insulin receptor to downstream targets IRS1, Akt/PKB, GSK3, Erk1/2 and ribosomal protein S6 in muscle, liver and adipose tissue in 5 h versus 16 h (overnight) fasted mice, and the time course (0-30 min) of these phosphorylation events. We also assessed whether re-feeding under 5 h and 16 h fasting conditions was a more robust stimulus than insulin alone. Conclusions: Our study determines that a short food withdrawal from mice, for a period of 5 h, results in a similar insulin-stimulated response in phosphorylation events as the long overnight fast, presenting a more physiological experimental set up. We also demonstrate that in vivo, insulin-stimulated phosphorylation of its signaling components is different between different peripheral tissues, and depending on the tissue(s) and protein(s) of interest, an appropriate time course should be chosen.     

随机饥饿和重喂食对小鼠能量代谢和行为的影响

为阐明能量代谢和行为的可塑性对动物适应食物资源变化的意义,将成年雄性KM 小鼠随机饥饿驯化4
周,再重喂食驯化4 周。采用食物平衡法测定摄食量、封闭式流体压力呼吸计测定基础代谢率(BMR) 和非颤
抖性产热(NST)、观察法测定行为。随机饥饿使摄食量、消化道重量显著增加,BMR 和NST 显著降低。与对照
组相比,饥饿组休息行为显著增加,活动显著降低。重喂食后,上述指标均恢复到对照组水平,表现出显著的
可塑性。研究结果表明,动物适应难以预测的食物资源短缺的主要策略包括:增加自由取食期间的摄食量;降
低BMR、NST 和活动行为,从而保存身体贮存的能量。能量代谢和活动行为在较短的时间尺度内表现出显著的
可塑性对小鼠适应不可预测的食物资源短缺的应激环境具有重要意义。     

Effect of starvation on glucose transport and membrane fluidity in rat intestinal epithelial cells

Studies on the surface area of microvilli (MV), fluidity of brush border membranes (BBM) and -glucose uptake were carried out in rat intestinal epithelial cells (IEC) during progressive starvation and under re-feed conditions. The surface area of MV, fluidity of BBM and -glucose transport through IEC membranes showed an increase during starvation when compared to well-fed controls. Re-feeding experiments restored the control values of all the three parameters within a short time. The results showed that the increase in -glucose transport through IEC membranes during starvation is due to increased surface area of MV and increased fluidity of BBM.     

摄食不同淀粉含量饲料对军曹鱼血清生化指标的影响

实验旨在研究经过10周投喂不同淀粉含量的饲料的养殖实验后, 禁食1d后再投喂对170 g军曹鱼血清生化指标的影响. 饲料以鱼粉为蛋白源, 鱼油、豆油、大豆卵磷脂为脂肪源, 分别添加0%(对照组)、6%、12%、18%、24%和30%的小麦淀粉(以微晶纤维素调平), 养殖实验期间每天饱食投喂2次. 结果表明, 饥饿再投喂饲料后各处理组军曹鱼血糖含量均在(0-5)h升高, 在5h时达到峰值, 并显著高于其他时间组, 摄食5h后开始下降, 7h时基本恢复到投喂前水平; 血清总蛋白含量在不同处理组以及同一处理组的不同时间点上均没有显著差异; 血清中甘油三酯含量在(0-5)h显著升高, 5h后其含量开始下降, 7h时基本恢复到投喂前水平. 其中0%、6%和12%组, 摄食5h后其甘油三酯含量显著高于摄食前与摄食后7h和24h, 而在18%、24%和30%组中, 其含量无显著差异; 0%淀粉组血清中胆固醇含量在(0-2)h显著升高, 2h时达到峰值, 在(2-7)h呈下降趋势, 之后趋于平稳. 其他处理组都是在(0-5)h升高, 5h后开始下降, 在7h时基本恢复到投喂前水平. 18%-30%组, 摄食后5h血清中胆固醇含量显著高于摄食前与摄食后24h. 军曹鱼血清中低密度脂蛋白-胆固醇在(0-5)h显著升高, 摄食5h后其含量开始下降, 7h时基本恢复到投喂前水平, 但各组不同时间点间均无显著性差异. 而血清中高密度脂蛋白-胆固醇含量除在24%添加组中, 摄食后5h显著高于摄食前(0h)及投喂结束后24h处理组, 其他处理之间无显著差异. 综上所述: 170 g军曹鱼禁食再摄入不同含量的小麦淀粉后其血清中血糖含量先升高后降低, 随着饲料中糖添加量的增加, 其峰值先增加, 后趋于平稳. 军曹鱼血清甘油三酯和胆固醇的含量会升高, 对其血清中低密度脂蛋白-胆固醇及高密度脂蛋白-胆固醇影响不显著.       

Mechanism of fasting heterothermia and re-feeding normothermia in mice

Mice subjected to caloric restriction (CR) typically display heterothermia characterized by hypothermia in the daytime and normothermia at night. The possible thermoregulatory mechanisms that mediate the CR-induced daytime hypothermia or the recovery of core temperature upon re-feeding are not well understood. In the present study drugs that inhibit three different pathways of thermogenesis were applied before, during and after CR in mice, while core temperature was monitored by biotelemetry. The time course of core temperature during complete CR and re-feeding was not modified by administration of the postganglionic adrenergic blocker guanethidine (10 mg/kg/day). Administration of the centrally acting muscle relaxant mephenesin (42 mg/kg/day) exacerbated the CR-induced hypothermia. Administration of the nonspecific opioid antagonist naloxone (20 mg/kg/day) also exacerbated the CR-induced hypothermia. None of the drugs had any effect on the rate of the rise in core temperature during re-feeding after a fast. It is concluded that mice may rely on the heat from motor activity to remain normothermic during the first night of complete fasting. Shivering thermogenesis appears to be critical in thermoregulation during fasting. Furthermore, opiate-dependent thermogenesis may also contribute to the regulation of body temperature during the second night of fasting.