Shelley Gorman

Exposomes and metabolic health through a physical activity lens: a narrative review

In this narrative review, we provide an overview of the role of physical activity as part of differing exposomes (our combined non-genetic exposures from conception onwards) and environmental influences on metabolic health. We discuss 'beneficial' exposomes (green/natural outdoor spaces, sun exposure, healthy diets and features of built environments) that could synergise with physical activity to prevent metabolic dysfunction, particularly that related to lifestyle diseases of obesity, type 2 diabetes and metabolic syndrome.

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.

Sun-health behaviours and attitudes towards sun safety amongst Australian teenagers: a qualitative update

This study aimed to explore current attitudes towards sun protection, and sun-seeking behaviour among young Australian adolescents. It was done as part of a larger project aiming to develop a digital resource to support young people in making informed sun-health decisions.

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.

SGLT2 Inhibitor-Induced Sympathoexcitation in White Adipose Tissue: A Novel Mechanism for Beiging

Recent preclinical data show that sodium glucose cotransporter 2 (SGLT2) inhibitors are able to reduce weight gain and induce beiging in white adipose tissue (WAT). We have previously shown that in neurogenic hypertensive Schlager (BPH/2J) mice, treatment with the SGLT2 inhibitor, Dapagliflozin, reduced blood pressure and prevented weight gain. Here we show that chemical sympathetic denervation achieved by systemic administration of 6-hydroxy-dopamine (6-OHDA) reduces body weight and the heightened sympathetic nervous system (SNS) innervation in WAT.

Low-dose UV radiation before running wheel access activates brown adipose tissue

When combined with physical activity, low-dose UVR may more effectively limit adiposity and modulate metabolic and immune pathways in iBAT

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

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

Sun exposure: An environmental preventer of metabolic dysfunction?

Emerging preclinical findings suggest that some sun exposure is necessary for optimal metabolic health

Maternal high fat diet compromises survival and modulates lung development of offspring, and impairs lung function of dams

While maternal high fat diet compromised litter survival, it also promoted somatic and lung growth (increased lung volume) in the offspring

Regular exposure to non-burning ultraviolet radiation reduces signs of non-alcoholic fatty liver disease in mature adult mice fed a high fat diet

Frequent exposure to low levels of sunlight may reduce the severity of hepatic steatosis induced in older adults living in environments of high caloric intake

Systematic Review of the Effects of Ultraviolet Radiation on Markers of Metabolic Dysfunction

Here we review the metabolic effects of exposure to ultraviolet radiation, focusing on the effects of phototherapies

Season, terrestrial ultraviolet radiation, and markers of glucose metabolism in children living in Perth, Western Australia

Increased safe sun exposure in winter therefore represents a plausible means of reducing fasting blood sugar in children with obesity

The challenges of developing and optimising an assay to measure 25-hydroxyvitamin D in saliva

We have developed an LC-MS/MS assay that accurately measures saliva 25(OH)D3 levels, which correlated with serum levels

Associations Between Sun Exposure and Adiposity Were Not Observed in Breast and Prostate Cancer Patients in a Cross-sectional Analysis

There were no statistically significant associations between time spent outdoors and adiposity

IFNβ inhibits the development of allergen tolerance and is conducive to the development of asthma on subsequent allergen exposure

Data indicate a role for Interferonβ in linking viral infection and allergy

High Dose Vitamin D supplementation alters faecal microbiome and predisposes mice to more severe colitis

High dose vitamin D supplementation is associated with a shift to a more inflammatory faecal microbiome and increased susceptibility to colitis

Investigating the roles of regulatory T cells, mast cells and interleukin-9 in the control of skin inflammat roles of regulatory T cells, mast cells and interleukin-9 in the control of skin inflammation by vitamin D. Arch Dermatol Res. 2018;310(3):221-30.

We investigated the ability of topical 1,25(OH)2D to suppress contact dermatitis through an IL9 dependent process, examining mast cells and IL9 secreting cells.

Ultraviolet radiation, Vitamin D and the development of obesity, metabolic syndrome and type-2 diabetes

Emerging findings suggest a protective role for ultraviolet radiation (UVR) and sun exposure in reducing the development of obesity and cardiometabolic dysfunction, but more epidemiological and clinical research is required that focuses on measuring the direct associations and effects of exposure to UVR in humans.

Sub-erythemal ultraviolet radiation reduces metabolic dysfunction in already overweight mice

Exposure to sunlight may limit cardiometabolic risk.

Vitamin D supplementation of initially vitamin D-deficient mice diminishes lung inflammation with limited effects on pulmonary epithelial integrity

In disease settings, vitamin D may be important for maintaining optimal lung epithelial integrity and suppressing inflammation, but less is known of its effects prior to disease onset.

High-dose intramuscular Vitamin D provides long-lasting moderate increases in serum 25-hydroxVitamin D levels and shorter-Term changes in plasma calcium

Intramuscular injection of a large bolus of Vitamin D effectively increases serum 25-hydroxyVitamin D levels without evidence of metabolic abnormality.

Clinical, research, and public health implications of poor measurement of Vitamin D status

New initiatives to develop a standard reference method and the assignment of "true" values to samples provide a solution to these problems.

A pathogenic role for the integrin CD103 in experimental allergic airways disease

Role for CD103 in the pathogenesis of experimental allergic airways disease in BALB/c mice through local control of CD4+ T cell and DC subset recruitment

Sun exposure and its effects on human health: Mechanisms through which sun exposure could reduce the risk of developing obesity and cardiometabolic dysfunction

The cardiometabolic protective effects of ultraviolet radiation and mechanistic pathways through which ultraviolet radiation could be beneficial.

Identification of genes differentially regulated by vitamin D deficiency that alter lung pathophysiology and inflammation in allergic airways disease

Vitamin D deficiency exacerbates house dust mite-induced inflammation and alterations in lung structure and function

Dietary Vitamin D Increases Percentages and Function of Regulatory T Cells in the Skin-Draining Lymph Nodes and Suppresses Dermal Inflammation

Dietary vitamin D3 increased the suppressive activity of regulatory T cells in the skin-draining lymph nodes, which are poised to suppress dermal inflammation

Vitamin D and allergic airway disease shape the murine lung microbiome in a sex-specific manner

Maintaining sufficient vitamin D is necessary for optimal lung health, and vitamin D may modulate the lung microbiome in a sex-specific fashion

Reduced immune responses in chimeric mice engrafted with bone marrow cells from mice with airways inflammation.

During respiratory inflammation, it is generally assumed that dendritic cells differentiating from the bone marrow are immunogenic rather than immunoregulatory.

Can skin exposure to sunlight prevent liver inflammation?

Here we discuss how skin exposure to sunlight may suppress liver inflammation and the severity of NAFLD.

The effects of in utero vitamin D deficiency on airway smooth muscle mass and lung function

In this study, we aimed to uncover the molecular mechanisms contributing to altered lung structure and function.

Comparing the effects of sun exposure and vitamin D supplementation on vitamin D insufficiency, and immune and cardio-metabolic function

Adults living in the sunny Australian climate are at high risk of skin cancer, but vitamin D deficiency (defined here as a serum 25-hydroxyvitamin D...

Vitamin D and immunity

The active form of vitamin D has an important role in calcium metabolism and in bone mineralisation, but the evidence for other health outcomes is mixed,...

Ultraviolet radiation suppresses obesity and symptoms of metabolic syndrome independently of vitamin D

UVR or sunlight exposure may be an effective means of suppressing the development of obesity and MetS, through mechanisms that are independent of vitamin D

Vitamin D status and ill health

This paper is a comment in response to a review of Vitamin D status and its association with ill health.

Vitamin D deficiency causes airway hyperresponsiveness and increases airway smooth muscle mass in the lungs of female BALB/c mice

We tested whether there is a causal association between vitamin D deficiency, airway smooth muscle (ASM) mass, and the development of airway hyperresponsiveness

Low maternal serum vitamin D during pregnancy and the risk for postpartum depression symptoms

Pregnancy is a time of vulnerability for vitamin D insufficiency, and there is an emerging literature associating low levels of 25(OH)-vitamin D with...

Characterization of regulatory dendritic cells differentiated from the bone marrow of UV-irradiated mice

In summary, UV-BMDCs do not express the classical phenotypic or gene expression properties of DCs reported by others as 'regulatory' or 'tolerogenic'.

Reversible Control by Vitamin D of Granulocytes and Bacteria in the Lungs of Mice: An Ovalbumin-Induced Model of Allergic Airway Disease

Vitamin D may be essential for restricting the development and severity of allergic diseases and asthma, but a direct causal link between vitamin D...

Altered immunity and dendritic cell activity in the periphery of mice after long-term engraftment with bone marrow from ultraviolet-irradiated mice

To investigate the immune capabilities of peripheral tissue DCs generated in vivo from the BM of UV-irradiated mice, chimeric mice were established.

Exposure to UV Wavelengths in Sunlight Suppresses Immunity. To What Extent is UV-induced Vitamin D3 the Mediator Responsible?

In experimental models, both vitamin D3-dependent and vitamin D3-independent pathways have been implicated in the mechanisms of UVR-induced systemic...

Prostaglandin E2 imprints a long-lasting effect on dendritic cell progenitors in the bone marrow

Injection of BM-differentiated DCs from nonchimeric mice restored the reduced immune responses of PGE2-chimeric mice.

Optimized 25-hydroxyvitamin D analysis using liquid-liquid extraction with 2D separation with LC/MS/MS detection, provides superior precision

The analysis of 25-hydroxyvitamin D3 (25(OH)D3) and related metabolites represents a considerable challenge for both clinical and research laboratories...

Immune modulation by UV: Role of vitamin D

In this chapter, evidence for and evidence against the involvement of vitamin D in the immunoregulatory properties of UV radiation is presented.

The current state of play of rodent models to study the role of vitamin D in UV-induced immunomodulation

Ultraviolet radiation (UVR) from sunlight is immunomodulatory and the main source of vitamin D for humans.

Acute Erythemal Ultraviolet Radiation Causes Systemic Immunosuppression in the Absence

Vitamin D is synthesised by ultraviolet (UV) irradiation of skin and is hypothesized to be a direct mediator.

Toward homeostasis: Regulatory dendritic cells from the bone marrow of mice with inflammation

Inflammatory mediators from peripheral tissues may control dendritic cell (DC) development in the bone marrow.

Vitamin D 3 deficiency enhances allergen-induced lymphocyte responses in a mouse model of allergic airway disease

In this study, using a mouse model, we determined whether vitamin D deficiency in utero and during early life modulated the severity of asthma.

Differences in control by UV radiation of inflammatory airways disease in naïve and allergen pre-sensitised mice

Exposure of skin to UV radiation (UVR) prior to allergen exposure can inhibit inflammatory airways disease in mice by reducing effector CD4+ T cells in both...

Modulation of the immune system by UV radiation: More than just the effects of vitamin D?

Humans obtain most of their vitamin D through the exposure of skin to sunlight

Vitamin D deficiency causes deficits in lung function and alters lung structure

The prevalence of vitamin D deficiency is increasing and has been linked to obstructive lung diseases including asthma and chronic obstructive pulmonary disease

Immune mechanisms by which topically applied vitamin D acts as a therapeutic agent

Vitamin D, nutrition, diet, therapeutic agent

Ultraviolet irradiation of mice reduces the competency of bone marrow-derived CD11c+

Direct UV irradiation of dendritic cells and Langerhans cells reduces their Ag presenting ability. However, the effects of UV on CD11c(+) cells located...

Topical 1,25-dihydroxyvitamin D3 subverts the priming ability of draining lymph node dendritic cells

The active form of vitamin D, 1,25-hydroxyvitamin D(3) [1,25(OH)(2)D(3)] is produced in skin following exposure to sunlight

Gene regulation by 1,25-dihydroxyvitamin D3 in CD4+CD25+ cells is enabled by IL-2

Vitamin D may be responsible for reducing the development and severity of autoimmune and allergic diseases. Topically applied 1,25-dihydroxyvitamin D(3) (1,25(O

Immune-modifying properties of topical vitamin D: Focus on dendritic cells and T cells

Topical creams containing the active form of vitamin D (1,25-dihydroxyvitamin D3; 1,25(OH)2D3) or analogues of this compound are currently used with some succes

1,25-dihydroxyvitamin D3 enhances the ability of transferred CD4+ CD25+ cells to modulate T helper type 2-driven asthmatic responses

The severity of allergic diseases may be modified by vitamin D. However, the immune pathways modulated by the active form of vitamin D, 1,25-dihydroxyvitamin D.

UV inhibits allergic airways disease in mice by reducing effector CD4 T cells

UV exposure and protection against allergic airways disease

Asthma is a chronic inflammatory disease of the small and large conducting airway mucosa characterised by Th2 cell immunity.

Quantifying the effectiveness of betaherpesvirus-vectored transmissible vaccines

Transmissible vaccines have the potential to revolutionize how zoonotic pathogens are controlled within wildlife reservoirs. A key challenge that must be overcome is identifying viral vectors that can rapidly spread immunity through a reservoir population.

The Effects of Using the Sun Safe App on Sun Health Knowledge and Behaviors of Young Teenagers: Results of Pilot Intervention Studies

A balanced approach toward sun exposure and protection is needed by young people. Excessive sun exposure increases their risk for skin cancers such as melanoma, whereas some exposure is necessary for vitamin D and healthy bones. We have developed a new iOS smartphone app-Sun Safe-through a co-design process, which aims to support healthy and balanced decision-making by young teenagers (aged 12-13 years).

Sex-Specific Environmental Impacts on Initiation and Progression of Multiple Sclerosis

The immunological mechanisms that contribute to multiple sclerosis (MS) differ between males and females. Females are 2-3 times more likely to develop MS compared to males, however the reason for this discrepancy is unknown. Once MS is established, there is a more inflammatory yet milder form of disease in females whereas males generally suffer from more severe disease and faster progression, neural degradation, and disability.

Developing an Online Tool to Promote Safe Sun Behaviors With Young Teenagers as Co-researchers

Despite education about the risks of excessive sun exposure, teenagers in Australia are sun-seeking, with sunburn common in summer. Conversely, some regular (time-limited) exposure to sunlight (that avoids sunburn) is necessary for vitamin D and healthy bones and other molecules important for immune and metabolic health. New interventions are thus required to better support teenagers to make healthy and balanced decisions about their sun behaviors.