Characterising nitric oxide-mediated metabolic benefits of low-dose ultraviolet radiation in the mouse: a focus on brown
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ARTICLE
Characterising nitric oxide-mediated metabolic benefits of low-dose ultraviolet radiation in the mouse: a focus on brown adipose tissue Gursimran K. Dhamrait 1 & Kunjal Panchal 1 & Naomi J. Fleury 1 & Tamara N. Abel 1 & Mathew K. Ancliffe 1 & Rachael C. Crew 2 & Kevin Croft 3 & Bernadette O. Fernandez 4 & Magdalena Minnion 4 & Prue H. Hart 1 & Robyn M. Lucas 5,6 & Peter J. Mark 2 & Martin Feelisch 4 & Richard B. Weller 7 & Vance Matthews 3 & Shelley Gorman 1 Received: 21 March 2019 / Accepted: 29 August 2019 # Springer-Verlag GmbH Germany, part of Springer Nature 2019
Abstract Aims/hypothesis Exposure to sunlight has the potential to suppress metabolic dysfunction and obesity. We previously demonstrated that regular exposure to low-doses of ultraviolet radiation (UVR) reduced weight gain and signs of diabetes in male mice fed a high-fat diet, in part via release of nitric oxide from skin. Here, we explore further mechanistic pathways through which lowdose UVR exerts these beneficial effects. Methods We fed mice with a luciferase-tagged Ucp1 gene (which encodes uncoupling protein-1 [UCP-1]), referred to here as the Ucp1 luciferase transgenic mouse (‘Thermomouse’) a high-fat diet and examined the effects of repeated exposure to low-dose UVR on weight gain and development of metabolic dysfunction as well as UCP-1-dependent thermogenesis in interscapular brown adipose tissue (iBAT). Results Repeated exposure to low-dose UVR suppressed the development of glucose intolerance and hepatic lipid accumulation via dermal release of nitric oxide while also reducing circulating IL-6 (compared with mice fed a high-fat diet only). Dietary nitrate supplementation did not mimic the effects of low-dose UVR. A single low dose of UVR increased UCP-1 expression (by more than twofold) in iBAT of mice fed a low-fat diet, 24 h after exposure. However, in mice fed a high-fat diet, there was no effect of UVR on UCP-1 expression in iBAT (compared with mock-treated mice) when measured at regular intervals over 12 weeks. More extensive circadian studies did not identify any substantial shifts in UCP-1 expression in mice exposed to low-dose UVR, although skin temperature at the interscapular site was reduced in UVR-exposed mice. The appearance of cells with a white adipocyte phenotype (‘whitening’) in iBAT induced by consuming the high-fat diet was suppressed by exposure to low-dose UVR in a nitric oxide-dependent fashion. Significant shifts in the expression of important core gene regulators of BAT function
Gursimran K. Dhamrait and Kunjal Panchal contributed equally to this study. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00125-019-05022-5) contains peer-reviewed but unedited supplementary material, which is available to authorised users. * Shelley Gorman [email protected]
4
Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton, UK
5
National Centre for Epidemiology and Population Health,
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