Determining the effects of low-dose ultraviolet radiation on the circadian rhythm of thermogenesis in brown adipose tissue of mice fed a high fat diet.

Obesity and its resulting co-morbidities place a huge burden on the Australian healthcare system and economy. Alterations to the body’s normal circadian rhythm increase the risk of developing obesity and metabolic dysfunction. Like most metabolically active tissues, circadian rhythm has been observed in brown adipose tissue (BAT) a site of thermogenesis, whereby heat is released via the process of uncoupled respiration, involving uncoupling protein-1 (UCP-1). Activation of thermogenesis in BAT has potential to treat metabolic dysfunction. We have previously shown that ongoing exposure to low dose ultraviolet radiation (UVR) curbed weight gain and limited metabolic dysfunction in mice fed a high fat diet through mechanisms involving skin release of nitric oxide(1). We hypothesised that regular exposure to low dose UVR (1 kJ/m2 UVB radiation, twice a week) would alter the circadian rhythm of thermogenesis in BAT of mice fed a high fat diet, through skin release of nitric oxide. The circadian rhythm of thermogenesis in BAT was examined by monitoring expression of the UCP-1, using UCP-1 luciferase transgenic (‘thermomouse’, FVB/NJ background, n=12/treatment) male mice. In this mouse, UCP-1 expression in the interscapular BAT (iBAT) was tracked by monitoring bioluminescence following their injection with the substrate luciferin. The circadian rhythm analyses involved measuring UCP-1 bioluminescence in iBAT, as well as blood glucose and and interscapular skin temperature at 4-6 hourly intervals over a 28 hours time-course. This was done at baseline, and after 6 and 12 weeks of feeding mice a high or low fat diet. There were four treatment groups in this 12-week study: 1. Mice fed a low-fat diet, and mock-irradiated (n=20); 2. Mice fed a high fat diet, and mock-irradiated (n=20); 3. Mice fed a high fat diet, and exposed twice a week to low dose UVR (1 kJ/m2)(n=20); or, 4. Mice fed a high fat diet and exposed twice a week to low dose UVR (1 kJ/m2) and topically treated with the nitric oxide scavenger, cPTIO (1 mM) (n=20). Signs of adiposity and metabolic dysfunction were also monitored by weighing mice, performing glucose and insulin tolerance tests, and measuring levels of liver steatosis via histopathology. Weak trends of circadian rhythmicity was noted in interscapular skin temperature during week 12. Ongoing UVR exposure to mice fed a high fat diet had moderately altered the level of UCP-1 expression in interscapular brown adipose tissue. Ongoing UVR exposure seemed to increase the potential of metabolic buffering in response to the high fat diet, and thus reducing the need for diet induced thermogenesis. More so, ongoing UVR suppressed the development of fatty liver disease in mice fed a high fat diet. The outcome of this study provides evidence that UVR exposure may suppress need for metabolic compensation in terms of diet-induced thermogenesis. The suppressive effects of UVR on signs of adiposity (e.g. hepatic steatosis and reduced WAT weights) were not linked with increased rates of thermogenesis in iBAT, in the absence of a circadian rhythm of UCP-1 expression in iBAT). And so if it is not the thermogenesis in BAT, it is important to examine the effects of UVR on other metabolic pathways and tissues as future focus.