Role of exercise, cold, and the biological clock on energy balance in humansThe ACTIBATE study

Abstract

Cold exposure has been proposed as a potential tool to face obesity since it is able to increase energy expenditure (i.e., cold induced thermogenesis – CIT). This increase is partially mediated by brown adipose tissue (BAT). Nevertheless, little is known yet about how CIT (specially its non-shivering component) and BAT metabolic activity are regulated, and which are the clinical implications of harnessing them in humans. Furthermore, most physiological functions in our organism are under the control of the biological clock, which shows a tight link with disease in humans. However, to date it remains unknown whether CIT and BAT activity follow a diurnal/circadian rhythmicity, and whether they are related to the general functioning of the circadian system. Furthermore, whether exercise and physical activity are efficient strategies to recruit and activate BAT still need to be explored. Therefore, the overall aim of the present Doctoral Thesis was to study the role of cold and the biological clock on energy balance in humans as well as on BAT; and to investigate whether exercise and physical activity could be potential strategies to recruit and activate BAT in humans. Mild cold elicits a modest increase in CIT and prompts a fat oxidative metabolism, especially during the initial moments of cold exposure (Study I). In addition, subjects exposed to the coldest ambient temperature during their daily life have 3-5 times more BAT volume and activity - measured as 18F-fluordeoxygelucose (18F-FDG) uptake - compared to subjects who are exposed to a warmer ambient temperature (Study II). CIT and BAT 18F-FDG uptake do not seem to have diurnal variations (Study III), and the relationship between the daily rhythm of distal skin temperature - an overall indicator of the circadian system functioning - and BAT 18F-FDG uptake, is masked by the environmental temperature (Study II). In addition, sleep duration and quality are not related to human BAT metabolic activity (Study IV). An acute aerobic exercise does not induce significant changes in the protein concentrations of UCP-1 (and therefore BAT activity) in mice (Study VI). Accordingly, physical activity levels and sedentary time are not related to BAT 18F-FDG uptake in young human adults (Study VII), neither to the regulation of browning markers, suggesting a negligible role for exercise and physical activity as potential strategies to recruit and activate human BAT. The results from the present Doctoral Thesis increase our knowledge on the effects of cold on energy and BAT metabolism in humans, and on how the biological clock and related factors might affect them. In addition, it provides novel information on the search of potential strategies to improve BAT function and browning of specific adipose depots.