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Wietse In het Panhuis, MSc

Prevention of cardiometabolic disorders related to circadian disturbances

Circadian disturbances (as occurring in for example shift work) have often been associated with metabolic and cardiovascular disorders. It is estimated that the prevalence of shift work in Europe is 15% and increasing. Shift work may therefore significantly contribute to public health issues, indicating the need for new interventions to reduce the adverse effects of circadian disruption.We have demonstrated that these associations may be causal as circadian disruption induced by prolonged light exposure led to adiposity in mice. Although the underlying cause remains to be determined, we suggest that that rhythm in brown adipose tissue (BAT) activity might be involved (Kooijman, PNAS USA 2015; van den Berg, Cell Reports 2018). BAT is characterized by its capacity to increase energy expenditure through thermogenesis by the uptake and combustion of glucose and fatty acids, thereby promoting lipid clearance from the circulation. This makes BAT a potential target for the prevention of cardiovascular disorders related to rhythm disturbances.

Alternatively, the effects of circadian disruption on atherosclerosis may be reduced by enhancing rhythm strength. Several environmental cues called zeitgebers signal the suprachiasmatic nucleus of the hypothalamus, also referred to as the master clock, which in turn regulates various metabolic processes. In case of rhythm disturbances, it takes a while for the circadian clock to adapt to a new rhythm. During this adaptation phase, alterations in metabolism result in an unfavourable metabolic profile. We hypothesize that increasing zeitgeber strength (e.g. by timing of physical activity and food intake) may enhance rhythm adaptation and thereby minimizes the adverse effects of circadian disruption.

My research focusses on the investigation of strategies to enhance rhythmic activity of BAT and rhythm adaptation. In preclinical setting I will evaluate if these strategies are able to alleviate the effects of circadian disruption on atherosclerosis.