Throughout evolution, humans have lived in synchrony with the natural light-dark cycle. Our bodies were used to going to sleep a few hours after dark, and waking up just before dawn. However, in... Show moreThroughout evolution, humans have lived in synchrony with the natural light-dark cycle. Our bodies were used to going to sleep a few hours after dark, and waking up just before dawn. However, in modern society the unambiguous availability of artificial light has desynchronized our biological clock from the naturally occurring day and night, with large consequences for metabolic health. This thesis sheds light on the negative health consequences of a disturbed biological clock, and elucidates novel approaches to prevent disease associated with chronic rhythm disruption, as occurs in shift work. We have identified important mechanisms through which rhythm disruption contributes to (cardio)metabolic disease, namely by exacerbating vascular inflammation and by deregulating rhythm in glucocorticoid hormone, thereby affecting the metabolic activity of tissues such as brown fat and bone. We continued by investigating two main approaches to prevent diseases associated with circadian disturbances: (1) by limiting disruption of the circadian timing system, and (2) by directly targeting the affected tissues. We found that timed feeding (1) and stimulation of the metabolic activity of brown fat (2) are both promising strategies to prevent and/or reduce (cardio)metabolic disease risk in the ever-increasing population of individuals who suffer from circadian disturbances. Show less
Cardiovascular diseases (CVD) are the leading cause of death worldwide, and disturbances in day-night rhythms have recently been implicated as a novel risk factor for CVD. We investigated the... Show moreCardiovascular diseases (CVD) are the leading cause of death worldwide, and disturbances in day-night rhythms have recently been implicated as a novel risk factor for CVD. We investigated the effects of modulating circadian rhythms on energy metabolism using animal models and by studying plasma metaoblites and lipids in humans. Using animal studies we observed that brown adipose tissue (BAT) is strongly regulated by the biological clock, possibly via circadian glucocorticoid rhythms, and attenuated BAT activity through prolonged light exposure increases adiposity. Research focusing on the rhythm in human BAT, and regulation thereof, is necessary to confirm the translational value of our findings. We also observed that mistimed light exposure enhances atherosclerosis development, which may provide a mechanistic link between the known association between shift work and CVD. We anticipate that living according to the natural circadian rhythms presumably contributes to cardiometabolic health. Since disturbances in day-night rhythms are inevitable in modern society, in the future we may advise individuals at risk for development of CVD refrain from shift work and short sleep duration. In addition, data in this thesis may be useful to design strategies to avoid the disadvantageous metabolic effects of shift work. Show less
