Abstract
摘要:由於每日二十四小時明暗周期的存在,幾乎所有地球上之生物體都發展出自發性的生物時鐘,預知每天轉換的環境以配合生理運作。因此,許多生理上的功能包括生物活動、荷爾蒙分泌、體溫,細胞週期以及代謝都受到生理時鐘的控制。大多數現代人,特別是有許多夜間工作者,以及旅人,因為夜晚暴露在光線中的時間延長,增加了夜間活動及飲食,而干擾了生理時鐘的運作,可知大眾的健康議題已引起相當的重視。在加上近年來的研究顯示,這些夜間工作者及旅人產生肥胖等健康問題的風險較高,且導致糖尿病、心血管疾病等等許多代謝相關之疾病。綜上所述,了解光線如何透過生理時鐘影響能量代謝將是十分重要的課題。
影響能量代謝及平衡有許多因素,其一即是腸道中的菌相。近年文獻指出,於一天中不同時期,腸內菌和宿主之間會有不同程度的交互作用,進而影響小腸上皮的生理恆定,而腸道內含菌與否也會影響腦內神經細胞的代謝產物。除此之外,腸內菌相的組成也對人類及小鼠的體重有所影響。
我們研究的初步結果表示,小鼠腸內不同細菌其菌量隨日夜周期有高低變化,顯示出腸內菌的組成會受到宿主生理時鐘調控的可能性。另外,已知自主感光神經膠細胞負責非景物成像的光線訊息,並控制這些訊息影響的生理功能,包括日夜周期及瞳孔光反射(Nature 476, 2011)。因此,自主感光神經膠細胞有可能會透過生理時鐘來調節腸內菌相,進而影響體重增減。藉上述原因,我們的計畫目標如以下三點:
(1)推斷光線如何透過與生理時鐘的作用影響體重增減
(2)檢視腸內菌相的組成如何受到光線以及宿主生理時鐘的調控
(3)推斷光線和腸內菌之間影響生物體能量代謝的機制
藉由探究光線影響生理時鐘的途徑,以及生理時鐘調控腸內菌組成的機制,我們將進一步了解生理時鐘受干擾如何危害健康,導致代謝性疾病。同時也有助我們提供更良好的夜間工作環境,希望可以減低夜間工作者因日夜節律失調而造成的健康危害。
Abstract: The 24 hours light dark cycle promotes the development of an intrinsic biological clock in almost all living organism on earth that help them anticipate the daily environmental oscillation. Thus, many physiological functions including activity cycle, hormone release, body temperature, cell cycle and metabolism are under control of circadian clock system. People who live in modern society, especially shift workers, have prolonged nighttime light exposure, increased nighttime activity and feeding. The disrupted light dark cycle may contribute to health problems, rising a significant concern on public health issue. Recent studies have shown that shift workers, world travelers have high risk of health problems such as cancer and obesity. And obesity could lead to metabolic diseases including diabetes and cardiovascular disease. Therefore, it is important to understand how light and circadian clock influence our energy balance.
The body metabolism and energy balance is under control of many factors including the bacteria in our digestive tract. Recent studies show that gut microbes interact with host in a circadian dependent manner to influence homeostasis of the intestinal epithelium. They also affect the metabolome in the brain. Moreover, the composition of gut microbiota has profound impact on the body weight of human and mouse. Our preliminary data shows that the concentration of different gut bacteria in mice fluctuated during the daily cycle, which suggest that the composition of microbiota in the gut may under the control of host circadian clock. Since intrinsically photosensitive retinal ganglion cells (ipRGCs) control many non-image forming light dependent functions including circadian clock and pupillary light reflex (Nature 476, 2011), they may also modulate gut microbes through circadian clock system, which influence the body weight with unknown mechanism. Therefore, our goals in this proposal are:
(1) Determine the effect of light and circadian interaction on body weight
(2) Reveal the composition of microbiota under the regulation of circadian clock and light
(3) Determine the mechanism of how circadian clock and microbiota influence the body metabolism
By determining the circuitry of light and circadian interaction and the circadian modulation of microbiota composition, we could further understand how disrupted light dark cycle leads to health problems. This information could also help us provide better environmental condition for people who work in special hours to reduce public health problems that due to disrupted daily cycle.
Keyword(s)
感光視神經
視黑質
糖尿病
體重
intrinsic photosensitive retinal ganglion cell melanopsin obesity