Title

A murine model for examining the effects of ultraviolet radiation and vitamin D deficiency on the expression of obesity-related metabolic syndrome

Date of Award

2013

Degree Type

Thesis

Degree Name

Bachelor of Science (Human Biology) Honours

School

School of Medical Sciences

Faculty

Health, Engineering and Science

First Advisor

Dr Shelley Gorman

Second Advisor

Associate Professor Mel Ziman

Abstract

Background: Obesity is one of the greatest public health issues affecting Australians. Obesity plays a key role in the development of the metabolic syndrome (MetS) and increases the risk of type-2 diabetes (T2D) and cardiovascular disease. Obese patients have reduced sunlight exposure through decreased outdoor physical activity and as a result, have low serum 25(OH)D levels. Additionally, there is a low-grade inflammation associated with obesity and MetS. Ultraviolet radiation (UVR) of skin can cause immunosuppression through soluble mediator release and DNA damage. I hypothesize that UVR may play a crucial role in reducing obesity and MetS.

Objective: The aim of this study was to develop a murine model to investigate the effects of UVR and vitamin D deficiency on the obesity-related metabolic syndrome by inducing cardiometabolic phenotypes in mice fed a high fat diet (HFD).

Method: Male C57Bl/6J mice were fed a vitamin D–null or –containing diet from 4 weeks of age. After 4 weeks on either diet they were switched to one of four diets; HFD (23.5%) or a low fat diet (LFD) (5%) that were supplemented or not with vitamin D. Mice were fed one of these diets for a further 12 weeks. The shaved dorsal skin of mice was exposed to no UVR, a sub-erythemal dose of UVR (1 kJ/m², twice a week) or an erythemal dose of UVR (4 kJ/m², once every 2 weeks) for the 12 weeks. Mice were weighed once a week to measure weight gain. At 0, 1, 2, 4, 6, 9 and 12 weeks after UVR and dietary intervention serum 25-hydroxyvitamin D levels were assessed. At 6 and 12 weeks post intervention, serum levels of triglyceride, calcium, glucose, cholesterol and TNFα were measured. The liver was also assessed histopathologically at these times to measure the extent of non-alcoholic fatty-liver disease (NAFLD) development. Glucose (5 and 10 weeks) and insulin tolerance (6 and 11 weeks) tests were performed post-intervention to determine the effects of skin exposure to UVR or dietary-induced vitamin D deficiency on the development of glucose intolerance and insulin resistance.

Results: Mice on the HFD gained weight more rapidly than those on a LFD and developed phenotypes reminiscent of obesity-related MetS. UVR significantly suppressed weight gain, insulin resistance, glucose fasting, non-alcoholic fatty liver disease (NAFLD) measures and serum levels of fasting insulin and glucose and cholesterol in mice fed a HFD. In contrast, only NAFLD measures, TNFα and LDL-cholesterol levels were improved in mice supplemented with vitamin D.

Conclusion: The effects of UVR observed in the mice fed a HFD were independent of vitamin D as serum 25-hydroxyvitmain D levels did not increase with skin exposure to UVR, as we have observed previously for male mice irradiated with UVR. These studies suggest that UVR (sunlight exposure) is more effective and may be more beneficial than vitamin D supplementation alone in reducing the development of obesity and MetS.

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