Early life nutrition, metabolic development and health
Project fact file
Professors Michael Symonds and Helen Budge
School / Division
Division of Child Health, Obstetrics and Gynaecology
Obesity is caused by an imbalance between energy intake and energy expenditure.
It is of immense global significance and worldwide predictions suggest a catastrophic epidemic of chronic obesity-related diseases as its prevalence rises further. It is well established that environmental factors play a critical role in determining long-term risk of developing both obesity and the resulting Type 2 diabetes. This concept has been highlighted by the dramatically increased occurrence of obesity Type 2 diabetes during childhood and there is currently a global epidemic of around 155 million obese children. These conditions were virtually unheard of in children 20 years ago. Europe is, therefore, facing an unprecedented health challenge and, within the United Kingdom for example, the prevalence doubled during the 1990s, so that by 2003 ~30% of children (3 million) were considered obese or overweight.
A potential target tissue in the prevention of obesity is the mechanism(s) which increase thermogenically active brown adipose tissue (BAT). This adipose tissue (or organ) is uniquely able to rapidly generate heat due to the biochemical function of uncoupling protein 1 (UCP1). Obese adults possess less BAT and ageing is associated with a decline in BAT activity. Recent studies have shown that discrete cells in white adipose tissue (WAT) also express UCP1. These cells, embedded in some WAT depots such as inguinal fat, are distinct from classical brown adipocytes, and are referred to as ‘beige’ adipocytes. Beige adipocytes are thought to be inducible and may play an important role in energy balance. Therefore, research aimed at preventing and/or treating obesity by increasing energy expenditure in BAT or through beiging of WAT is one of a number of approaches currently being developed in order to prevent or cure human metabolic disease.
In BAT and beige WAT, the rate of energy expenditure is controlled by the expression of the UCP1 gene. The expression of this gene is regulated by signals from the sympathetic nervous system, released in response to an environmental stimulus such as diet or temperature. The signalling cascade in response to warm and cold stimuli is complex, including several areas of the brain from the pre-optical area through hypothalamus and brain stem and is signalled by common neurotransmitters, e.g. glutamate. The sympathetic nervous system connects, among other tissues, to BAT and releases norepinephrine, which binds to beta-adrenergic receptors and induces UCP1 transcription, which can again be moderated by complicating factors.
Emerging research in developmental programming is increasingly demonstrating that alterations in the maternal environment, particularly maternal obesity, can influence the intrauterine development of the fetus and influence the offspring’s risk of obesity and Type 2 diabetes over the life course. Stimulation of thermogenesis both before and during pregnancy may affect the fetus’ in utero environment and, with that, the offspring’s long term metabolic health, but this mechanism has not been investigated.
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