植物次生代谢产物对哺乳动物生物钟的调节作用

生物钟是生物适应地球自转而形成的内在节律,哺乳动物体内生物钟与内分泌、代谢调控以及疾病均有着紧密联系。随着人类生活和工作模式的改变,生物钟紊乱已经逐渐影响到机体健康。研究发现,饮食在为机体提供物质能量的同时,也是调节生物钟的重要途径之一,并且不同物质的摄入对生物钟的调控也存在差异。现就几种植物次生代谢产物,如白藜芦醇、茶多酚和咖啡因等对生物钟调节的研究进展进行综述。     

哺乳动物营养代谢的时间生物学研究进展

时间生物学主要是研究生物体内生理和行为的时间机制的学科,而这种机制主要是由生物钟调控的。研究表明,营养代谢的各个方面如葡萄糖转运、糖原异生、脂质合成及降解、氧化磷酸化等作用都受到生物钟核心转录机制的调控,并具有时间敏感性;相反,代谢信号也可以反馈调节生物钟系统,包括生物钟基因表达和行为活动。生物钟的紊乱会造成诸如心血管疾病、肥胖、糖尿病等多种疾病。本文从代谢与生物钟的相互关系、各类营养信号和营养素对生物钟的作用以及生物钟与营养代谢相关疾病的关系等多方面综述了哺乳动物营养代谢的时间生物学研究进展。     

哺乳动物生物钟与能量代谢的相关研究进展

生物钟广泛存在于各种生物体中,是生命体的一种内源调节机制。哺乳动物生物钟系统与机体营养代谢和能量平衡有着密切的关系。概述了生物钟系统通过营养途径、限速酶途径、核受体途径对哺乳动物机体代谢活动和能量平衡的调控,以及哺乳动物代谢稳态对生物钟系统的影响,从而为从生物钟调控的角度治疗和防控代谢综合征提供新的思路。     

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。     

生物钟节律与肝脏代谢稳态

生物钟(circadian clock)是机体内在的自主性计时系统,包括视交叉上核(suprachiasmatic nucleus, SCN)中枢生物钟与各组织外周生物钟。分子生物钟的核心机制包括CLOCK/BMAL1二聚体诱导抑制因子CRYs和PERs的转录,CRYs/PERs复合物反馈抑制前者转录活性,进而使这些生物钟核心因子以及节律输出基因的转录水平呈24 h振荡的反馈调节核心环路,以及REV-ERBα和RORα调控BMAL1转录的补充环路。机体大约80%的蛋白编码基因表达呈现明显的昼夜节律性特征,生物钟系统使生物能够适应地球自转所产生的昼夜节律(近日节律),使机体的代谢平衡与能量相互协同。生物钟与代谢稳态相互依存、互为基础,使机体能够高效利用能量,协同机体不同组织,快速适应内外环境变化。肝脏作为机体代谢的中枢器官,其进行的各种生理活动几乎都受到生物钟的控制。生物钟与肝脏代谢调控之间存在多重交互调控机制,两者的交互平衡失调是代谢性疾病的高风险因素。本文主要就肝脏的糖、脂和蛋白质代谢的节律性调控进行了综述,并强调了线粒体功能的振荡,讨论了肝脏代谢对生物钟的反馈调节,并对生物钟研究方法和应用进行展望。     

生命中不能承受之轻——微重力条件下生物昼夜节律的变化研究

生物钟是地球上绝大多数生物经过长期演化形成的一种内在机制,可以调控生物的生理、代谢和行为的节律,以适应地球因自转而产生的近24小时的昼夜周期。人类在空间探索过程中由于环境因素与地表环境的巨大差异,生理和健康面临很大的压力。在诸多环境因子中,重力变化对生物钟具有重要的影响。迄今人们已对人及多种生物在微重力环境中的变化规律进行了研究,但微重力调控生物钟的分子机制仍很不清楚。现将对此方面的研究概况和进展进行综述。     

进食行为调控外周生物钟节律的研究进展

哺乳动物的生物钟包括位于下丘脑视交叉神经上核中的中枢生物钟(central clock)以及外周组织生物钟(peripheral clock)。节律正常时,由中枢时钟决定的外周生物钟同时具有一定程度的独立性。食物牵引实验(food entrainment)证明改变进食时间(白天给食)可以完全逆转外周组织的节律,因此,对于外周组织,进食是一个重要的授时因子(synchronizer)。目前已报道多种进食相关信号调控外周生物钟基因的表达及节律。现就进食行为影响外周生物钟等方面的研究进行综述。     

节律性转录因子驱动哺乳动物昼夜节律生物钟简

生物体通过内在的昼夜节律生物钟调整生理行为和代谢生化反应来适应昼夜环境周期性变化。哺乳动物的昼夜节律生物钟核心连锁环通过驱动特异性的转录因子来维持整个基因组转录的节律性。生物钟与代谢的内稳态密切相关,生物钟的紊乱会引起各种疾病,该领域的研究能够促进时间疗法的发展来维持生命的健康,甚至可以延缓衰老。     

生物钟基因介导卵巢功能调控的分子机制研究

地球的自转产生了以24 h为周期的昼夜节律,因此生物的生理过程和行为活动大都呈现一个近似24 h的周期节律改变,以适应环境的不断变化。昼夜节律在整体水平是一个系统性的调控,它的产生、维持和调控依赖于细胞内生物钟基因的震荡型转录翻译负反馈环路。研究表明,生物钟在卵巢动情周期和生殖系统发育过程中发挥重要作用。本篇综述主要阐述了自卵巢生物钟发现后的种种研究成果,包括卵巢生物钟对类固醇激素生成及排卵的影响,生物钟基因对生育能力的影响,以及生物钟调控与女性生殖系统疾病的相关性。     

节律性转录因子驱动哺乳动物昼夜节律生物钟

生物体通过内在的昼夜节律生物钟调整生理行为和代谢生化反应来适应昼夜环境周期性变化。哺乳动物的昼夜节律生物钟核心连锁环通过驱动特异性的转录因子来维持整个基因组转录的节律性。生物钟与代谢的内稳态密切相关,生物钟的紊乱会引起各种疾病,该领域的研究能够促进时间疗法的发展来维持生命的健康,甚至可以延缓衰老。     

Metabolism as an integral cog in the mammalian circadian clockwork

Abstract

Circadian rhythms are an integral part of life. These rhythms are apparent in virtually all biological processes studies to date, ranging from the individual cell (e.g. DNA synthesis) to the whole organism (e.g. behaviors such as physical activity). Oscillations in metabolism have been characterized extensively in various organisms, including mammals. These metabolic rhythms often parallel behaviors such as sleep/wake and fasting/feeding cycles that occur on a daily basis. What has become increasingly clear over the past several decades is that many metabolic oscillations are driven by cell-autonomous circadian clocks, which orchestrate metabolic processes in a temporally appropriate manner. During the process of identifying the mechanisms by which clocks influence metabolism, molecular-based studies have revealed that metabolism should be considered an integral circadian clock component. The implications of such an interrelationship include the establishment of a vicious cycle during cardiometabolic disease states, wherein metabolism-induced perturbations in the circadian clock exacerbate metabolic dysfunction. The purpose of this review is therefore to highlight recent insights gained regarding links between cell-autonomous circadian clocks and metabolism and the implications of clock dysfunction in the pathogenesis of cardiometabolic diseases.     

Adaptive Significance of Circadian Clocks

Circadian clocks are ubiquitous and are found in organisms ranging from bacteria to mammals. This ubiquity of occurrence implies adaptive significance, but to date there has been no rigorous empirical evidence to support this. It is believed that an organism possessing circadian clocks gains fitness advantage in two ways: (i) by synchronizing its behavioral and physiological processes to cyclic environmental factors (extrinsic adaptive value); (ii) by coordinating its internal metabolic processes (intrinsic adaptive value). There is preliminary circumstantial evidence to support both. Several studies using organisms living in constant environments have shown that these organisms possess functional circadian clocks, suggesting that circadian clocks may have some intrinsic adaptive value. Studies to assess the adaptive value of circadian clocks in periodic environments suggest that organisms may have a fitness advantage in those periodic environments, which closely match their own intrinsic periodicity. Furthermore, evidence from organisms living in the wild, selection studies, and studies on latitudinal clines suggest that circadian clocks may have an extrinsic adaptive value as well. In this paper, I have presented several hypotheses for the emergence of circadian clocks and have reviewed some major empirical studies suggesting adaptive significance of circadian clocks.     

Adaptive significance of circadian clocks

Circadian clocks are ubiquitous and are found in organisms ranging from bacteria to mammals. This ubiquity of occurrence implies adaptive significance, but to date there has been no rigorous empirical evidence to support this. It is believed that an organism possessing circadian clocks gains fitness advantage in two ways: (i) by synchronizing its behavioral and physiological processes to cyclic environmental factors (extrinsic adaptive value); (ii) by coordinating its internal metabolic processes (intrinsic adaptive value). There is preliminary circumstantial evidence to support both. Several studies using organisms living in constant environments have shown that these organisms possess functional circadian clocks, suggesting that circadian clocks may have some intrinsic adaptive value. Studies to assess the adaptive value of circadian clocks in periodic environments suggest that organisms may have a fitness advantage in those periodic environments, which closely match their own intrinsic periodicity. Furthermore, evidence from organisms living in the wild, selection studies, and studies on latitudinal clines suggest that circadian clocks may have an extrinsic adaptive value as well. In this paper, I have presented several hypotheses for the emergence of circadian clocks and have reviewed some major empirical studies suggesting adaptive significance of circadian clocks.     

To be or not to be rhythmic? A review of studies on organisms inhabiting constant environments

Abstract

Circadian clocks are endogenous time keeping mechanisms that drive near 24-h behavioural, physiological and metabolic rhythms in organisms. It is thought that organisms possess circadian clocks to facilitate coordination of essential biological events to the external day and night (extrinsic advantage) so as to enhance Darwinian fitness. However, on Earth, there are a number of habitats that are not subject to such robust daily cycling of geo-physical factors. Do organisms living under such conditions exhibit rhythmic behaviours that are driven by endogenous circadian clocks? We attempt to critically survey studies of rhythms (or the lack of them) in organisms living in a range of constant environments. Many such organisms do show rhythms in behaviour and/or physiological variables. We suggest that such presence of rhythms may be indicative of an underlying clock that facilitates, (a) internal synchrony among rhythms, and (b) temporal partitioning of incompatible cellular processes (intrinsic advantage). We then highlight reasons that limit our interpretations about the presence (or absence) of clocks in such organisms living under constant conditions, and suggest possible methods to conclusively test whether or not rhythms in these organisms are driven by endogenous circadian clocks with the hope that it may enhance our understanding of circadian clocks in organisms under constant environments.