| The onset of obesity leads to a plethora of other health problems including cardiovascular disease, diabetes, and cancer. It is characterized by an expansion of adipose mass to accommodate the excess of energy that is available to the body. In the past few decades the number of obese people has escalated worldwide. Concurrent with this escalation in obesity, there has also been an increase in vitamin D deficiency. Until now, the correlation between the vitamin D receptor (VDR) and energy metabolism has not been explored in an animal model. Using loss of function and gain of function mouse models, we have systematically investigated the role of the VDR in energy metabolism. Studies performed on global VDR knockout mice [VDR(-/-)], have shown that ablation of the VDR leads to an increase in global metabolism resulting in a decrease in body fat percentage. This lean phenotype is at least partially due to the upregulation of uncoupling proteins (UCPs) and the increase in beta-oxidation observed in primary white adipocytes. To further investigate the role of the VDR in adipocyte biology, we overexpressed the VDR specifically in the adipose tissue (aP2-hVDR). These mice exhibited the opposite phenotype of the VDR(-/-) mice. The aP2-hVDR mice were prone to diet-induced obesity, probably due to a decrease in energy expenditure. This decrease in energy expenditure can be partially explained by the decrease in locomotor activity observed in these mice. Additionally, the white adipose tissue from the aP2-hVDR mice displayed decreased levels of lipolysis, which may also explain the increase in fat mass. Taken together these data indicate a previously unknown role of the VDR in the regulation of global energy expenditure and adipocyte biology. |
