生物钟与肠道菌群调控哺乳动物能量代谢研究进展

生物钟作为哺乳动物进化过程中产生的一种适应机体内外环境昼夜变化的内在机制,控制着机体的睡眠-觉醒及进食等生理活动,使生物体在每个昼夜周期的能量需求和营养供给呈现出与环境相适应的节律性变化。哺乳动物的肝脏、骨骼肌、胰腺、心血管等组织的葡萄糖代谢、脂质代谢和激素分泌等都受到生物钟的调控。作为宿主特殊的“器官”,肠道菌群在共同进化过程中与宿主微环境(组织、细胞、代谢产物)构成了一个微生态系统,在宿主对营养物质的消化和吸收过程中发挥重要作用。近年来的一些研究证据表明,肠道菌群的构成、数量、定植以及功能活动均具有显著的昼夜节律性变化,而这与生物钟调控下的各种生理功能变化是密切相关的。此外,有研究发现肠道菌群可通过分解宿主无法消化的膳食纤维等营养物质产生短链脂肪酸等代谢产物,部分代谢产物具有调节宿主生物钟并影响代谢的功能。本文将重点阐述生物钟与肠道菌群的互作及其对哺乳动物能量代谢的影响,以期为代谢性疾病的预防和治疗提供新的线索和思路。     

昼夜节律钟调控代谢的研究进展

生理和行为的昼夜节律性调控对健康生活是必需的。越来越多的流行病学和遗传学证据显示昼夜节律的破坏与代谢紊乱性疾病相关联。在分子水平上,昼夜节律受到时钟蛋白组成的转录一翻译负反馈环的调控。时钟蛋白通过以下两种途径调节代谢：首先,时钟蛋白作为转录因子直接调节一些代谢关键步骤的限速酶和代谢相关核受体的表达,其次作为代谢相关核受体的辅调节因子来激活或抑制其转录活性。虽然时钟蛋白对代谢途径的调节导致代谢物水平呈昼夜节律振荡,但是产生的代谢物反过来又可以影响昼夜节律钟基因的表达,进而影响昼夜节律钟。深入研究昼夜节律钟与代谢的交互调节可能为治疗某些代谢紊乱性疾病提供新的治疗方案。     

白头鹎体温、体重及能量代谢的昼夜节律

动物的生理昼夜节律是对环境昼夜变化的一种重要适应。为探讨白头鹎(Pycnonotus sinensis)体温、体重及能量代谢的昼夜节律变化,采用数字式温度计、电子天平及封闭式流体压力呼吸仪,测定了白头鹎的日体温、日体重和昼夜基础代谢率(BMR)。结果发现:白头鹎日体温及日体重变化存在显著差异,其中夜间体温明显低于白昼,并在4:00时体温呈现最低值;而白头鹎夜间体重显著低于白昼,在4:00时达到最小值,在18:00时达到最大值。另外,白头鹎的BMR也表现出了明显的昼夜差异,夜间BMR显著低于白昼。表明白头鹎体温、体重及能量代谢存在显著的昼夜节律变化,并调节达到自身生理能量平衡,从而适应昼夜环境变化。     

昼夜节律系统与成人昼夜节律睡眠觉醒障碍

昼夜节律是存在于所有生命体中、接近24小时的内源性生物节律。昼夜节律与社会或环境节律的长期不同步,会引起睡眠、情绪等一系列变化。本文阐述了昼夜节律系统与睡眠之间的联系,重点介绍成人昼夜节律睡眠觉醒障碍疾病的临床研究成果,以期加强临床医生对该病的认识和诊治。     

肠道菌群昼夜节律与宿主生物节律相互作用的研究进展

为了适应地球昼夜更替对机体的影响,哺乳动物进化出了一套内在的适应性计时机制,由此形成了生物钟系统（circadian clock）。昼夜节律作为该系统中的重要部分可与机体的代谢过程同步变化[1]。肠道菌群作为与机体共生的生物群落,在肠道功能方面发挥着重要作用。对肠道菌群的昼夜节律性波动以及与宿主生物节律之间的相互作用进行研究有重要意义。本文将着重阐述肠道菌群昼夜节律与宿主生物节律的相互作用,以及这种相互作用对宿主代谢的影响。     

粘球藻固氮作用与几种能量代谢过程的关系

本文以单细胞蓝藻（粘球藻）为材料,研究了固氮作用与光合作用,呼吸代谢以及氢代谢等能量代谢过程的关系,发现光照是固氮作用的主要限制因子,在光下的有氧分解过程和氧化磷酸化反应是推动固氮作用的能量来源,抑制光合磷酸化或氧化磷酸化反应都能导至固氮作用的显著降低,但用DCMU抑制光系统II电子传递过程却意外地能大幅度提高固氮活性,在暗中的粘球藻固氮主要靠有氧分解过程支持,粘球藻与其它固氮生物相似,在没有可利用的还原底物存在或正常固氮作用被特异性和抑制时,可以将固氮酶所截获能量的大部分用于释放分子氢和回收氢,但未发现通过吸氢反应来推动固氮作用。     

果蝇昼夜节律的分子机制研究进展

果蝇由于遗传易操作性而成为一个研究昼夜节律分子机制的理想模式生物 . 到目前为止,通过遗传学和生物化学方法已经鉴定到 10 多个时钟基因 (clock genes) 和许多时钟相关基因,包括时钟输入基因和钟控基因 . 这些时钟基因以及它们的相应产物组成两个互相依赖的转录 / 翻译反馈环路,从而调节行为和生理的昼夜节律 . 果蝇这种核心钟的工作原理同样见于哺乳动物 .     

哺乳动物似昼夜节律研究概要

本文参阅了50年代以来有关昼夜节律研究的重要著作,并根据近年来国内外发表的节律研究论文综合整理写成。     

乳腺癌细胞能量代谢特点

乳腺癌是严重威胁女性健康的最常见的恶性肿瘤之一。在乳腺癌的恶性转化过程中,癌细胞能量代谢变化是癌细胞的主要特征并促进癌细胞增殖。乳腺癌细胞通过增加葡萄糖代谢产生能量。近年来,人们对代谢改变的复杂机制进行了深入研究,参与这些过程的基因被用作乳腺癌的临床治疗靶点。本文总结近年来与乳腺癌细胞异常代谢特征、调节机制、它们之间的联系以及相关治疗策略相关的最新发现,以期为乳腺癌的预防、诊断、及治疗提供新的思路。     

分析小鼠昼夜节律变化的行为学方法

昼夜节律是指生命活动以24小时为周期的内在性节律.为了适应昼夜环境周期性的变化,地球上几乎所有生物体,包括藻类、细菌、植物、动物等,都演化出一个特殊的系统——生物钟,用以指挥不同组织与器官来适应环境的昼夜交替,维持机体的生理稳态和行为与环境昼夜变化同步.生物钟是指由内源性分子时钟控制的日周生理振荡过程,人类生命活动的各...     

Circadian rhythms of indoleamines and serotonin N-acetyltransferase activity in the pineal gland

Conclusion The circadian rhythm of melatonin synthesis in the pineal glands of various species has been summarized. The night-time elevation of melatonin content is in most if not all cases regulated by the change of N-acetyltransferase activity. In mammals, the N-acetyltransferase rhythm is controlled by the central nervous system, presumably by suprachiasmatic nuclei in hypothalamus through the superior cervical ganglion. In birds, the circadian oscillator that regulates the N-acetyltransferase rhythm is located in the pineal glands. The avian pineal gland may play a biological clock function to control the circadian rhythms in physiological, endocrinological and biochemical processes via pineal hormone melatonin.     

Circadian rhythms in the retina of rats with photoreceptor degeneration

Previous studies have demonstrated that the mammalian retina contains a circadian clock system that controls several retinal functions. In mammals the location of the retinal circadian clock is unknown whereas, in non-mammalian vertebrates, earlier work has demonstrated that photoreceptor cells contain the circadian clock. New experimental evidence has suggested that in mammals the retinal circadian clock may be located outside the photoreceptor cells. In this study we report that circadian rhythms in Aa-nat mRNA (in vivo) and melatonin synthesis (in vitro) are still present in the retina of rats lacking photoreceptors. The circadian pacemaker(s) controlling such rhythms is probably located in kainic acid sensitive neurons in the inner retina since kainic acid injections abolished the rhythmicity. These data are the first direct demonstration that circadian rhythmicity in the mammalian retina can be generated independently from the photoreceptors and the suprachiasmatic nuclei of the hypothalamus.     

The Role of Circadian Clocks in Metabolic Disease

The circadian clock is a highly conserved timing system, resonating physiological processes to 24-hour environmental cycles. Circadian misalignment is emerging as a risk factor of metabolic disease. The molecular clock resides in all metabolic tissues, the dysfunction of which is associated with perturbed energy metabolism. In this article, we will review current knowledge about molecular mechanisms of the circadian clock and the role of clocks in the physiology and pathophysiology of metabolic tissues.     

Social synchronization of circadian rhythms of metabolism in honeybees (Apis mellifera)

ABSTRACT. Groups of honeybee workers ( Apis mellifera Linn.; Hymenoptera: Apidae) show endogenous circadian rhythms in metabolic activity. Workers entrained to two different photoperiods, when put together in a group, coordinate their individual metabolic activity cycles into a synchronized group oscillation. Either physical interaction among workers, or a low volatility contact pheromone, is implicated in the control of this oscillating system.     

Circadian and seasonal rhythms in the behavior of spinner dolphins (Stenella longirostris)

The present study investigated both circadian and seasonal fluctuations in the daytime activities of the spinner dolphin, Stenella longirostris , from the Fernando de Noronha Archipelago in Brazil. The number of dolphins, and aerial, and reproductive activities were documented. The observations were carried out from January 1997 to December 2001. Temporal series and rhythmic characteristics (mesor, rhythmic percentage, and acrophase) were obtained by COSINOR analysis and later compared. The dolphins entered the bay in the morning, displayed aerial and reproductive activities during daytime, and left the bay in late afternoon to the open ocean. This study indicated that the rainy season affected the three behaviors investigated decreasing the rhythms parameter and advancing the beginning of these activities. The number of individuals was higher during the dry season and the animals stayed longer inside the bay. During the dry season, there was a bimodal expression of aerial activity, expressing a longer use of the temporal niche than in the rainy season. The phases with high frequencies of aerial activity seemed associated with those showing high reproductive activity, both with peak frequencies at about 0800. The results represent an important contribution to the advancement of chronobiological studies, and to the biology of cetaceans, considering that the existence of circadian and seasonal rhythms was proven in the behavior of spinner dolphins in an area of the SW Atlantic. Moreover, it allows restricting periods of the day for the activities of tourism as a form of minimizing the impacts of the boats on the dolphins.     

Comparative Circadian Metabolomics Reveal Differential Effects of Nutritional Challenge in the Serum and Liver

Diagnosis and therapeutic interventions in pathological conditions rely upon clinical monitoring of key metabolites in the serum. Recent studies show that a wide range of metabolic pathways are controlled by circadian rhythms whose oscillation is affected by nutritional challenges, underscoring the importance of assessing a temporal window for clinical testing and thereby questioning the accuracy of the reading of critical pathological markers in circulation. We have been interested in studying the communication between peripheral tissues under metabolic homeostasis perturbation. Here we present a comparative circadian metabolomic analysis on serum and liver in mice under high fat diet. Our data reveal that the nutritional challenge induces a loss of serum metabolite rhythmicity compared with liver, indicating a circadian misalignment between the tissues analyzed. Importantly, our results show that the levels of serum metabolites do not reflect the circadian liver metabolic signature or the effect of nutritional challenge. This notion reveals the possibility that misleading reads of metabolites in circulation may result in misdiagnosis and improper treatments. Our findings also demonstrate a tissue-specific and time-dependent disruption of metabolic homeostasis in response to altered nutrition.