Impact of maternal vitamin D deficiency on body composition: the role of muscle and fat development

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The overall aim of the research proposal is to determine the importance of maternal vitamin D status during early development on health implications across the lifespan of offspring.Vitamin D is a micronutrient with a well established role in growth and maintenance of the skeletal system and regulation of calcium homeostasis and numerous studies have associated low blood 25(OH)D concentrations with musculoskeletal function including rickets, osteomalacia, osteopenia, osteoporosis and increased incidence of fractures across the lifespan. However vitamin D receptor (VDR) is expressed in several tissues suggesting a wide range of biological function. Researchers have found that vitamin D status may be associated with other conditions including obesity, insulin resistance, cardiovascular disease and the metabolic syndrome. Low sun exposure, reduced dietary vitamin D intake, and older age are the most common factors associated with vitamin D deficiency (VDD) and the prevalence of VDD is approximately 1 billion worldwide and the rate of insufficiency is higher in female than male population. In the UK 67% of pregnant/lactating women are vitamin D deficient which is worrying as evidence suggests that vitamin D maybe critical for maternal health and normal foetal and/or postnatal development. Fetal vitamin D concentrations are predominantly dependent on maternal levels and there is a growing body of evidence suggesting that suboptimal levels of vitamin D during development can have a negative impact on wellbeing through impacts on muscle and adipose tissues. Vitamin D inadequacy during pregnancy has been associated with increased risk of preeclampsia, development of gestational diabetes and caesarean section in the mother while numerous studies have shown that infants have low birth weights, are small for gestational age, have reduced bone growth, poor skeletal mineralization and lower bone mineral content and by the age of 6 have greater fat mass. While in vivo studies have shown a significant increase in proliferation and lipid droplets in pre-adipocytes from mice exposed to VDD environment during development. Increased lipid deposition within muscle has been associated with functional limitations in muscle performance and an increase in inflammation and atrophy of muscle tissue leading to a decline in muscle functionality. In addition lipid accumulation in skeletal muscle is a significant risk factor for insulin resistance and development of diabetes. The origin and cellular localisation of this fat is unclear, but one possibility is that it forms when myogenic precursor cells present in the muscle transdifferentiate into mature adipocytes as suggested by our previous studies. Low physiological concentrations (a vitamin D deficient state) resulted in increased formation of lipid droplets in C2C12 cells, a muscle cell line, and increased markers of adipogenesis. Thus, we propose that a lack of vitamin D during development may favour adipogenesis at the expense of muscle development. Thus, combining both in vitro and in vivo approaches the aim of this project is to determine whether a lack of vitamin D during pregnancy influences cellular processes involved in the development of skeletal muscle and adipose tissue in the foetuses and whether these subsequently affect energy expenditure and overall body composition of the resulting offspring.