Sunlight: Time for a Rethink?

UVR is a skin carcinogen, yet no studies link sun exposure to increased all-cause mortality. Epidemiological studies from the United Kingdom and Sweden link sun exposure with reduced all-cause, cardiovascular, and cancer mortality. Vitamin D synthesis is dependent on UVB exposure. Individuals with higher serum levels of vitamin D are healthier in many ways, yet multiple trials of oral vitamin D supplementation show little benefit. Growing evidence shows that sunlight has health benefits through vitamin D-independent pathways, such as photomobilization of nitric oxide from cutaneous stores with reduction in cardiovascular morbidity. Sunlight has important systemic health benefit as well as risks.

UVR and RPE - The Good, the Bad and the degenerate Macula.

Ultraviolet Radiation (UVR) has a well-established causative influence within the aetiology of conditions of the skin and the anterior segment of the eye. However, a grounded assessment of the role of UVR within conditions of the retina has been hampered by a historical lack of quantitative, and spectrally resolved, assessment of how UVR impacts upon the retina in terms congruent with contemporary theories of ageing. In this review, we sought to summarise the key findings of research investigating the connection between UVR exposure in retinal cytopathology while identifying necessary avenues for future research which can deliver a deeper understanding of UVR's place within the retinal risk landscape.

Cutaneous leishmaniasis in a newly established treatment centre in the Lay Gayint district, Northwest Ethiopia.

Background: Cutaneous leishmaniasis (CL) is a neglected tropical disease that primarily affects the most vulnerable populations. In Ethiopia, where this study took place, CL is an important health problem, however, the incidence of CL is poorly monitored. Objectives: This study took place in a recently established CL treatment centre, at Nefas Mewcha Hospital, Lay Gayint. This area was considered to be endemic for CL, however, no cases of CL from Lay Gayint had previously been officially reported to the Amhara Regional Health Bureau. Methods: Following a CL awareness campaign, a retrospective data review was performed of patients presenting to this centre between July 2019 and March 2021. Basic demographic and clinical data were collected by a nurse and recorded in the logbook of the CL treatment centre. Results: Two hundred and one patients presented for diagnosis and treatment. The age of the patients ranged from 2 to 75 years and 63.2% were males. Most patients were between 10- and 19-years-old. The majority (79.1%) of the patients presented with localised cutaneous leishmaniasis and 20.9% with mucocutaneous leishmaniasis. 98% of the patients tested positive for Leishmania parasites by microscopy. Conclusions: This work underpinned how CL is a major public health problem in the Lay Gayint district. It also shows that raising awareness about CL in the community and providing diagnosis and treatment encouraged patients to travel to seek diagnosis and treatment.

Dupilumab significantly improves sleep in adults with atopic dermatitis: results from the 12-week placebo-controlled period of the 24-week phase IV randomized double-blinded placebo-controlled DUPISTAD study.

BACKGROUND: Sleep disturbance is a prominent symptom of atopic dermatitis (AD) and can result in insomnia, daytime fatigue, drowsiness, reduced productivity and impaired quality of life (QoL). OBJECTIVES: The Dupilumab Effect on Sleep in AD Patients (DUPISTAD) phase IV randomized double-blinded placebo-controlled study evaluated the impact of dupilumab treatment on sleep and other patient- and physician-reported outcomes. METHODS: Adults with moderate-to-severe AD were randomized 2 : 1 to dupilumab 300 mg once every 2 weeks (q2w) or placebo for 12 weeks; concomitant topical corticosteroids were permitted. Patients subsequently entered an open-label phase and received dupilumab 300 mg q2w for a further 12 weeks. The primary endpoint was the percentage change in sleep quality from baseline to week 12, assessed using a novel numeric rating scale (NRS). Secondary and exploratory endpoints included percentage change in peak pruritus NRS (PP NRS), change in SCORing Atopic Dermatitis (SCORAD), SCORAD sleep visual analogue scale (VAS), Eczema Area and Severity Index, Patient-Reported Outcomes Measurement Information System (PROMIS) sleep-related impairment T-score and the Epworth Sleepiness Scale. Sleep diary and wrist actigraphy measurements were recorded throughout the study. RESULTS: In total, 127 patients received dupilumab and 61 patients received placebo. Demographic and baseline disease characteristics were balanced between groups. Sleep quality NRS significantly improved in patients treated with dupilumab by week 12 vs. placebo [least squares mean of the difference (LSMD) -15.5%, P < 0.001]. PP NRS (LSMD -27.9%, P < 0.001), SCORAD (LSMD -15.1, P < 0.001), SCORAD sleep VAS (LSMD -2.1, P < 0.001) and PROMIS T-score (LSMD -3.6, P < 0.001) were also significantly improved at week 12 with dupilumab vs. placebo. The overall percentage of patients reporting treatment-emergent adverse events was lower in the dupilumab group (56.7%) than in the placebo group (67.2%). CONCLUSIONS: Dupilumab significantly improved sleep quality and perception of sleep continuity, itch, metrics of AD severity and QoL in adults with moderate-to-severe AD, with an acceptable safety profile compared with placebo.

A mechanistic evaluation of human beta defensin 2 mediated protection of human skin barrier in vitro.

The human skin barrier, a biological imperative, is impaired in inflammatory skin diseases such as atopic dermatitis (AD). Staphylococcus aureus is associated with AD lesions and contributes to pathological inflammation and further barrier impairment. S. aureus secretes extracellular proteases, such as V8 (or 'SspA'), which cleave extracellular proteins to reduce skin barrier. Previous studies demonstrated that the host defence peptide human beta-defensin 2 (HBD2) prevented V8-mediated damage. Here, the mechanism of HBD2-mediated barrier protection in vitro is examined. Application of exogenous HBD2 provided protection against V8, irrespective of timeline of application or native peptide folding, raising the prospect of simple peptide analogues as therapeutics. HBD2 treatment, in context of V8-mediated damage, modulated the proteomic/secretomic profiles of HaCaT cells, altering levels of specific extracellular matrix proteins, potentially recovering V8 damage. However, HBD2 alone did not substantially modulate cellular proteomic/secretomics profiles in the absence of damage, suggesting possible therapeutic targeting of lesion damage sites only. HBD2 did not show any direct protease inhibition or induce expression of known antiproteases, did not alter keratinocyte migration or proliferation, or form protective nanonet structures. These data validate the barrier-protective properties of HBD2 in vitro and establish key protein datasets for further targeted mechanistic analyses.

The effect of daily UVA phototherapy for 2 weeks on clinic and 24-h blood pressure in individuals with mild hypertension.

Latitude and season determine exposure to ultraviolet radiation and correlate with population blood pressure. Evidence for Vitamin D causing this relationship is inconsistent, and temperature changes are only partly responsible for BP variation. In healthy individuals, a single irradiation with 20 J/cm2 UVA mobilises NO from cutaneous stores to the circulation, causes arterial vasodilatation, and elicits a transient fall in BP. We, therefore, tested whether low-dose daily UVA phototherapy might be an effective treatment for mild hypertension. 13 patients with untreated high-normal or stage 1 hypertension (BP 130-159/85-99 mm Hg), confirmed by 24-h ambulatory blood pressure (ABP), were recruited. Using home phototherapy lamps they were either exposed to 5 J/cm2 full body UVA (320-410 nm) radiation each day for 14 days, or sham-irradiated with lamps filtered to exclude wavelengths <500 nm. After a washout period of 3 ± 1 week, the alternate irradiation was delivered. 24-h ABP was measured on day 0 before either irradiation sequence and on day 14. Clinic BP was recorded on day 0, and within 90 min of irradiation on day 14. There was no effect on 24-h ABP following UVA irradiation. Clinic BP shortly after irradiation fell with UVA (-8.0 ± 2.9/-3.8 ± 1.1 mm Hg p = 0.034/0.029) but not sham irradiation (1.1 ± 3.0/0.9 ± 1.5 mm Hg). Once daily low-dose UVA does not control mildly elevated BP although it produces a transient fall shortly after irradiation. More frequent exposure to UVA might be effective. Alternatively, UVB, which photo-releases more NO from skin, could be tried.

Rash morphology as a predictor of COVID-19 severity: A systematic review of the cutaneous manifestations of COVID-19.

Approximately 6% of those with COVID-19 will experience cutaneous manifestations. Examining data from this cohort could provide useful information to help with the management of COVID-19. To that end, we conducted a systematic review primarily to assess rash morphologies associated with COVID-19 and their relationship with disease severity. Secondary outcomes include demographics, distribution, dermatological symptoms, timeline, diagnostic method and medication history. The literature was searched for all patients with skin manifestations thought to be related to suspected or confirmed COVID-19. Patients with a history of dermatological, rheumatological or occupational skin disorders were excluded. Of the 2056 patients selected, the most common morphologies were chilblain-like lesions (54.2%), maculopapular (13.6%) and urticaria (8.3%). Chilblain-like lesions were more frequent in the younger population (mean age 21.5, standard deviation ± 10.8) and were strongly linked with milder disease, not requiring an admission (odds ratio [OR] 35.36 [95% confidence interval {CI} 23.58, 53.03]). Conversely, acro-ischaemia and livedo reticularis were associated with worse outcomes, including a need for ICU (OR 34.01 [95% CI 16.62, 69.57] and OR 5.57 [95% CI 3.02, 10.30], respectively) and mortality (OR 25.66 [95% CI 10.83, 60.79] and OR 10.71 [95% CI 4.76, 24.13], respectively). Acral lesions were the most common site (83.5%). 35.1% experienced pruritus, 16.4% had pain and 4.7% reported a burning sensation. 34.1% had asymptomatic lesions. Rash was the only symptom in 20.9% and occurred before or alongside systemic symptoms in 12.4%. 28.3% had a positive polymerase chain reaction nasopharyngeal swab and 5.4% had positive antibodies, while 21.9% tested negative and 45.1% were not tested. In conclusion, COVID-19 causes a variety of rashes, which may cause symptoms and add to morbidity. Rash type could be helpful in determining COVID-19 prognosis.

A Real-World Data Study on the Healthcare Resource Use for Uncontrolled Moderate-to-Severe Atopic Dermatitis in Secondary Care in the United Kingdom Prior to the Introduction of Biologic Treatment.

Background: Whilst there is international evidence around the high healthcare resource utilization (HRU) associated with atopic dermatitis (AD), there is a lack of published data from the United Kingdom (UK). Methods: A retrospective, descriptive, observational study was conducted to evaluate the burden of moderate-to-severe AD on the National Health Service (NHS) in an adult UK population treated with traditional standard of care prior to the introduction of biologics. Patients (n=59) were recruited from 6 UK NHS Hospital Trusts and observed over three years. Results: 707 dermatology clinic visits were recorded over the observation period, amounting to 6.6 visits per patient-year, most commonly for routine check-ups most of which involved dermatology consultants (n=469, 66%). Physicians were the most consulted healthcare professional (n=652, 92%); emollients were the most common treatment (n=80 courses). 174 flares requiring additional medical advice were recorded in total (1.6 per patient-year). Discussion/Conclusions: Complex treatment pathways for adult patients in the UK with moderate-to-severe AD incur considerable HRU, particularly for those patients non-responsive to systemic therapies with broad immunosuppressant action. Recent advances in biologics-based AD management could possibly have a significant positive impact on HRU through significant reduction in the number of NHS touch points identified in this study.

Risks and Benefits of UV Radiation.

While UV radiation is a skin carcinogen, this should not obscure the growing evidence that sunlight has significant health benefits, including impacts on cardiovascular and metabolic health. Epidemiological and mechanistic evidences for the importance of different wavelengths of sunlight, including blue light and UV radiation, are presented.

Metabolic dysfunction induced by a high-fat diet modulates hematopoietic stem and myeloid progenitor cells in brown adipose tissue of mice.

Brown adipose tissue (BAT) may be an important metabolic regulator of whole-body glucose. While important roles have been ascribed to macrophages in regulating metabolic functions in BAT, little is known of the roles of other immune cells subsets, particularly dendritic cells (DCs). Eating a high-fat diet may compromise the development of hematopoietic stem and progenitor cells (HSPCs)-which give rise to DCs-in bone marrow, with less known of its effects in BAT. We have previously demonstrated that ongoing exposure to low-dose ultraviolet radiation (UVR) significantly reduced the 'whitening' effect of eating a high-fat diet upon interscapular (i) BAT of mice. Here, we examined whether this observation may be linked to changes in the phenotype of HSPCs and myeloid-derived immune cells in iBAT and bone marrow of mice using 12-colour flow cytometry. Many HSPC subsets declined in both iBAT and bone marrow with increasing metabolic dysfunction. Conversely, with rising adiposity and metabolic dysfunction, conventional DCs (cDCs) increased in both of these tissues. When compared with a low-fat diet, consumption of a high-fat diet significantly reduced proportions of myeloid, common myeloid and megakaryocyte-erythrocyte progenitors in iBAT, and short-term hematopoietic stem cells in bone marrow. In mice fed the high-fat diet, exposure to low-dose UVR significantly reduced proportions of cDCs in iBAT, independently of nitric oxide release from irradiated skin [blocked using the scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide potassium salt (cPTIO)], but did not significantly modify HSPC subsets in either tissue. Further studies are needed to determine whether changes in these cell populations contribute towards metabolic dysfunction .

Higher Sun Exposure in the First Trimester Is Associated With Reduced Preterm Birth; A Scottish Population Cohort Study Using Linked Maternity and Meteorological Records.

Background: Preterm birth (birth at <37 weeks gestation) is the leading cause of death in children under 5-years-old, and prevention is a global public health issue. Seasonal patterns of preterm birth have been reported, but factors underlying this have been poorly described. Sun exposure is an important environmental variable that has risks and benefits for human health, but the effects of sun exposure on pregnancy duration and preterm birth are unknown. Objectives: To determine the association between available sun exposure and preterm birth. Methods: We performed a population-based data-linkage study of 556,376 singleton births (in 397,370 mothers) at or after 24 weeks gestation, in Scotland between 2000 and 2010. Maternity records were linked to available sun exposure from meteorological records, by postcode. Logistic regression analysis was used to explore the relationship between available sunshine and preterm birth at <37 weeks gestation. Exploratory analyses included a subgroup analysis of spontaneous and indicated preterm births and a sibling analysis in sib pairs discordant for preterm birth. Results: The rate of preterm birth was 6% (32,958/553,791 live births). Increased available sun exposure in the first trimester of pregnancy was associated with a reduced risk of preterm birth, with evidence of a dose-response. Compared with the lowest quartile of sun exposure, the highest quartile of sun exposure was associated with a reduced odds ratio (OR) of preterm birth of 0.90 (95% Confidence Interval (CI) 0.88-0.94 p < 0.01) on univariable analysis and OR of 0.91 (95% CI 0.87, 0.93 p < 0.01) after adjustment for second trimester sunlight exposure, parity, maternal age, smoking status, and deprivation category. No association was seen between preterm birth and second trimester available sun exposure or combined first and second trimester exposure. Similar patterns were seen on sibling analysis and within both the indicated and spontaneous preterm subgroups. Discussion: Available sun exposure in the first trimester of pregnancy is associated with a protective effect on preterm birth <37 weeks gestation. This opens up new mechanisms, and potential therapeutic pathways, for preterm birth prevention.

Nitric oxide (NO) and nanoparticles - Potential small tools for the war against COVID-19 and other human coronavirus infections.

The endogenous free radical nitric oxide (NO) plays a pivotal role in the immunological system. NO has already been reported as a potential candidate for use in the treatment of human coronavirus infections, including COVID-19. In fact, inhaled NO has been used in clinical settings for its antiviral respiratory action, and in the regulation of blood pressure to avoid clot formation. In this mini-review, we discuss recent progress concerning the antivirus activity of NO in clinical, pre-clinical and research settings, and its beneficial effects in the treatment of clinical complications in patients infected with coronaviruses and other respiratory viral diseases, including COVID-19. We also highlight promising therapeutic effects of NO donors allied to nanomaterials to combat COVID-19 and other human coronavirus infections. Nanomaterials can be designed to deliver sustained, localized NO release directly at the desired application site, enhancing the beneficial effects of NO and minimizing the side effects. Challenges and perspectives are presented to open new fields of research.

Insufficient Sun Exposure Has Become a Real Public Health Problem.

This article aims to alert the medical community and public health authorities to accumulating evidence on health benefits from sun exposure, which suggests that insufficient sun exposure is a significant public health problem. Studies in the past decade indicate that insufficient sun exposure may be responsible for 340,000 deaths in the United States and 480,000 deaths in Europe per year, and an increased incidence of breast cancer, colorectal cancer, hypertension, cardiovascular disease, metabolic syndrome, multiple sclerosis, Alzheimer's disease, autism, asthma, type 1 diabetes and myopia. Vitamin D has long been considered the principal mediator of beneficial effects of sun exposure. However, oral vitamin D supplementation has not been convincingly shown to prevent the above conditions; thus, serum 25(OH)D as an indicator of vitamin D status may be a proxy for and not a mediator of beneficial effects of sun exposure. New candidate mechanisms include the release of nitric oxide from the skin and direct effects of ultraviolet radiation (UVR) on peripheral blood cells. Collectively, this evidence indicates it would be wise for people living outside the tropics to ensure they expose their skin sufficiently to the sun. To minimize the harms of excessive sun exposure, great care must be taken to avoid sunburn, and sun exposure during high ambient UVR seasons should be obtained incrementally at not more than 5-30 min a day (depending on skin type and UV index), in season-appropriate clothing and with eyes closed or protected by sunglasses that filter UVR.

Photochemistry of nitric oxide and S-nitrosothiols in human skin.

Nitric oxide (NO) is related to a wide range of physiological processes such as vasodilation, macrophages cytotoxicity and wound healing. The human skin contains NO precursors (NOx). Those are mainly composed of nitrite (NO2-), nitrate (NO3-), and S-nitrosothiols (RSNOs) which forms a large NO store. These NOx stores in human skin can mobilize NO to blood stream upon ultraviolet (UV) light exposure. The main purpose of this study was to evaluate the most effective UV light wavelength to generate NO and compare it to each NO precursor in aqueous solution. In addition, the UV light might change the RSNO content on human skin. First, we irradiated pure aqueous solutions of NO2- and NO3- and mixtures of NO2- and glutathione and NO3- and S-nitrosoglutathione (GSNO) to identify the NO release profile from those species alone. In sequence, we evaluated the NO generation profile on human skin slices. Human skin was acquired from redundant plastic surgical samples and the NO and RSNO measurements were performed using a selective NO electrochemical sensor. The data showed that UV light could trigger the NO generation in skin with a peak at 280-285 nm (UVB range). We also observed a significant RSNO formation in irradiated human skin, with a peak at 320 nm (UV region) and at 700 nm (visible region). Pre-treatment of the human skin slice using NO2- and thiol (RSHs) scavengers confirmed the important role of these molecules in RSNO formation. These findings have important implications for clinical trials with potential for new therapies.

Does Incident Solar Ultraviolet Radiation Lower Blood Pressure?

Background Hypertension remains a leading global cause for premature death and disease. Most treatment guidelines emphasize the importance of risk factors, but not all are known, modifiable, or easily avoided. Population blood pressure correlates with latitude and is lower in summer than winter. Seasonal variations in sunlight exposure account for these differences, with temperature believed to be the main contributor. Recent research indicates that UV light enhances nitric oxide availability by mobilizing storage forms in the skin, suggesting incident solar UV radiation may lower blood pressure. We tested this hypothesis by exploring the association between environmental UV exposure and systolic blood pressure (SBP) in a large cohort of chronic hemodialysis patients in whom SBP is determined regularly. Methods and Results We studied 342 457 patients (36% black, 64% white) at 2178 US dialysis centers over 3 years. Incident UV radiation and temperature data for each clinic location were retrieved from the National Oceanic and Atmospheric Administration database. Linear mixed effects models with adjustment for ambient temperature, sex/age, body mass index, serum Na+/K+ and other covariates were fitted to each location and combined estimates of associations calculated using the DerSimonian and Laird procedure. Pre-dialysis SBP varied by season and was ≈4 mm Hg higher in black patients. Temperature, UVA and UVB were all linearly and inversely associated with SBP. This relationship remained statistically significant after correcting for temperature. Conclusions In hemodialysis patients, in addition to environmental temperature, incident solar UV radiation is associated with lower SBP. This raises the possibility that insufficient sunlight is a new risk factor for hypertension, perhaps even in the general population.

Investigating the Potential for Ultraviolet Light to Modulate Morbidity and Mortality From COVID-19: A Narrative Review and Update.

During the COVID-19 (coronavirus disease of 2019) pandemic, researchers have been seeking low-cost and accessible means of providing protection from its harms, particularly for at-risk individuals such as those with cardiovascular disease, diabetes and obesity. One possible way is via safe sun exposure, and/or dietary supplementation with induced beneficial mediators (e.g., vitamin D). In this narrative review, we provide rationale and updated evidence on the potential benefits and harms of sun exposure and ultraviolet (UV) light that may impact COVID-19. We review recent studies that provide new evidence for any benefits (or otherwise) of UV light, sun exposure, and the induced mediators, vitamin D and nitric oxide, and their potential to modulate morbidity and mortality induced by infection with SARS-CoV-2 (severe acute respiratory disease coronavirus-2). We identified substantial interest in this research area, with many commentaries and reviews already published; however, most of these have focused on vitamin D, with less consideration of UV light (or sun exposure) or other mediators such as nitric oxide. Data collected to-date suggest that ambient levels of both UVA and UVB may be beneficial for reducing severity or mortality due to COVID-19, with some inconsistent findings. Currently unresolved are the nature of the associations between blood 25-hydroxyvitamin D and COVID-19 measures, with more prospective data needed that better consider lifestyle factors, such as physical activity and personal sun exposure levels. Another short-coming has been a lack of measurement of sun exposure, and its potential to influence COVID-19 outcomes. We also discuss possible mechanisms by which sun exposure, UV light and induced mediators could affect COVID-19 morbidity and mortality, by focusing on likely effects on viral pathogenesis, immunity and inflammation, and potential cardiometabolic protective mechanisms. Finally, we explore potential issues including the impacts of exposure to high dose UV radiation on COVID-19 and vaccination, and effective and safe doses for vitamin D supplementation.

Delivering nitric oxide into human skin from encapsulated S-nitrosoglutathione under UV light: An in vitro and ex vivo study.

Nitric oxide (NO) is a crucial molecule in the human body. The encapsulation of exogenous NO donors into chitosan nanoparticles (CS NPs) has been widely used to overcome NO drawbacks in pharmacological applications, such as, its short half-life. The NO donor, S-nitrosoglutathione (GSNO), was encapsulated into CS NPs (GSNO-CS NPs) and characterized by AFM and DLS measurements. The nanoparticles presented a hydrodynamic size of 123.3 ± 1.5 nm and a polydispersity of 0.25 ± 0.01. The ability of GSNO-CS NPs, combined with UV irradiation, to deliver NO was evaluated using ex vivo human skin. The human skin was pre-treated with GSNO-CS NPs, in the presence and absence of UV irradiation. The results showed that the combined treatment significantly increased the NO and S-nitrosothiol levels in human skin. This effect can emulate the cardiovascular benefits related to NO without negative side effects of skin exposure to UV light.

Characterising nitric oxide-mediated metabolic benefits of low-dose ultraviolet radiation in the mouse: a focus on brown adipose tissue.

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.