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视交叉上核驱动餐后甘油三酯摄入骨骼肌和棕色脂肪组织的昼夜变化。

The suprachiasmatic nucleus drives day-night variations in postprandial triglyceride uptake into skeletal muscle and brown adipose tissue.

作者信息

Moran-Ramos Sofía, Guerrero-Vargas Natali N, Mendez-Hernandez Rebeca, Basualdo Maria Del Carmen, Escobar Carolina, Buijs Ruud M

机构信息

Department of Anatomy, Faculty of Medicine, Universidad Nacional Autonóma de México, Mexico City, Mexico.

Department of Cell Biology and Physiology, Institute for Biomedical Research, Universidad Nacional Autonoma de Mexico, Mexico City, Mexico.

出版信息

Exp Physiol. 2017 Dec 1;102(12):1584-1595. doi: 10.1113/EP086026. Epub 2017 Nov 7.

DOI:10.1113/EP086026
PMID:29113012
Abstract

What is the central question of this study? What are the factors influencing day-night variations in postprandial triglycerides? What is the main finding and its importance? Rats show low postprandial plasma triglyceride concentrations early in the active period that are attributable to a higher uptake by skeletal muscle and brown adipose tissue. We show that these day-night variations in uptake are driven by the suprachiasmatic nucleus, probably via a Rev-erbα-mediated mechanism and independent of locomotor activity. These findings highlight that the suprachiasmatic nucleus has a major role in day-night variations in plasma triglycerides and that disturbances in our biological clock might be an important risk factor contributing to development of postprandial hyperlipidaemia. Energy metabolism follows a diurnal pattern, mainly driven by the suprachiasmatic nucleus (SCN), and disruption of circadian regulation has been linked to metabolic abnormalities. Indeed, epidemiological evidence shows that night work is a risk factor for cardiovascular disease, and postprandial hyperlipidaemia is an important contributor. Therefore, the aim of this work was to investigate the factors that drive day-night variations in postprandial triglycerides (TGs). Intact and SCN-lesioned male Wistar rats were subjected to an oral fat challenge during the beginning of the rest phase (day) or the beginning of the active phase (night). The plasma TG profile was evaluated and tissue TG uptake assayed. After the fat challenge, intact rats showed lower postprandial plasma TG concentrations early in the night when compared with the day. However, no differences were observed in the rate of intestinal TG secretion between day and night. Instead, there was a higher uptake of TG by skeletal muscle and brown adipose tissue early in the active phase (night) when compared with the rest phase (day), and these variations were abolished in rats bearing bilateral SCN lesions. Rev-erbα gene expression suggests this as a possible mediator of the mechanism linking the SCN and day-night variations in TG uptake. These findings show that the SCN has a major role in day-night variations in plasma TGs by promoting TG uptake into skeletal muscle and brown adipose tissue. Consequently, disturbance of the biological clock might be an important risk factor contributing to the development of hyperlipidaemia.

摘要

本研究的核心问题是什么?影响餐后甘油三酯昼夜变化的因素有哪些?主要发现及其重要性是什么?大鼠在活跃期早期餐后血浆甘油三酯浓度较低,这归因于骨骼肌和棕色脂肪组织的摄取增加。我们发现,这些摄取的昼夜变化由视交叉上核驱动,可能通过一种由Rev-erbα介导的机制,且与运动活动无关。这些发现突出表明,视交叉上核对血浆甘油三酯的昼夜变化起主要作用,并且我们生物钟的紊乱可能是导致餐后高脂血症发生的一个重要风险因素。能量代谢遵循昼夜模式,主要由视交叉上核(SCN)驱动,昼夜节律调节的破坏与代谢异常有关。事实上,流行病学证据表明,夜间工作是心血管疾病的一个风险因素,而餐后高脂血症是一个重要促成因素。因此,本研究的目的是探究驱动餐后甘油三酯(TGs)昼夜变化的因素。在休息期(白天)开始或活跃期(夜间)开始时,对完整的和视交叉上核损伤的雄性Wistar大鼠进行口服脂肪激发试验。评估血浆TG谱并测定组织TG摄取。脂肪激发试验后,与白天相比,完整大鼠在夜间早期餐后血浆TG浓度较低。然而,白天和夜间肠道TG分泌速率未观察到差异。相反,与休息期(白天)相比,活跃期(夜间)早期骨骼肌和棕色脂肪组织对TG的摄取更高,并且在双侧视交叉上核损伤的大鼠中这些变化消失。Rev-erbα基因表达表明其可能是连接视交叉上核与TG摄取昼夜变化机制的介质。这些发现表明,视交叉上核通过促进TG摄取到骨骼肌和棕色脂肪组织中,在血浆TG的昼夜变化中起主要作用。因此,生物钟紊乱可能是导致高脂血症发生的一个重要风险因素。

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