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 low-dose 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 (Dio2, increased more than twofold), fatty acid transport (increased Fatp2 [also known as Slc27a2]), lipolysis (decreased Atgl [also known as Pnpla2]), lipogenesis (decreased Fasn) and inflammation (decreased Tnf), and proportions of macrophages (increased twofold) were observed in iBAT of mice exposed to low-dose UVR. These effects were independent of nitric oxide released from skin. CONCLUSIONS/INTERPRETATION Our results suggest that non-burning (low-dose) UVR suppresses the BAT 'whitening', steatotic and pro-diabetic effects of consuming a high-fat diet through skin release of nitric oxide, with some metabolic and immune pathways in iBAT regulated by UVR independently of nitric oxide.

中文翻译：

---

表征小鼠低剂量紫外线辐射的一氧化氮介导的代谢益处：着眼于棕色脂肪组织。

目的/假说暴露在阳光下有可能抑制代谢功能障碍和肥胖。先前我们证明了，低剂量的紫外线辐射（UVR）的定期暴露会降低饲喂高脂饮食的雄性小鼠的体重增加和糖尿病的征兆，部分原因是一氧化氮从皮肤中释放出来。在这里，我们探讨了低剂量UVR发挥这些有益作用的其他机理途径。方法我们给小鼠饲喂带有荧光素酶标记的Ucp1基因（编码解偶联蛋白1 [UCP-1]），此处将其称为Ucp1荧光素酶转基因小鼠（'Thermomouse'）高脂饮食，并研究了重复食用的影响。暴露于小剂量UVR会增加肩inter间棕色脂肪组织（iBAT）的体重增加和新陈代谢功能障碍的发展以及UCP-1依赖的生热作用。结果反复暴露于低剂量UVR可以通过皮肤释放一氧化氮抑制葡萄糖耐受不良和肝脂质蓄积的发展，同时还可以降低循环IL-6（与仅饲喂高脂饮食的小鼠相比）。膳食硝酸盐补充剂不能模拟低剂量UVR的影响。在暴露后24小时，低剂量饮食喂养的小鼠在iBAT中，单次低剂量的UVR可使UCP-1表达增加（超过两倍）。但是，在以高脂饮食喂养的小鼠中，在12周内定期测量时，UVR对iBAT中的UCP-1表达没有影响（与模拟治疗的小鼠相比）。尽管暴露于UVR的小鼠肩s间部位的皮肤温度降低，但更广泛的昼夜节律研究并未发现暴露于低剂量UVR的小鼠UCP-1表达有任何实质性变化。通过以一氧化氮依赖性方式暴露于低剂量的UVR，可以抑制因食用高脂饮食而在iBAT中出现白色脂肪细胞表型（“增白”）的细胞的出现。BAT功能的重要核心基因调节因子（Dio2，增加了两倍以上），脂肪酸转运（Fatp2增加（也称为Slc27a2）），脂解（Atgl减少（又称为Pnpla2）），脂肪生成（重要的基因表达变化）在暴露于低剂量UVR的小鼠的iBAT中观察到巨噬细胞比例（Fasn降低）和炎症（Tnf降低）以及巨噬细胞比例（增加了两倍）。这些作用与皮肤释放出的一氧化氮无关。结论/解释我们的结果表明，不燃烧（低剂量）的UVR可以抑制BAT的“增白”，