Obesity is a major public health threat.
While recent changes in the patterns of obesity in the population are certainly driven by environmental changes, the heritability of obesity is extremely strong. Thus, identical twins who are brought up in different families, will usually have very similar amounts, and distribution, of body fat in adult life, bearing little resemblance to the families into which they were adopted.
Researchers at the Institute of Metabolic Science have played a world-leading role in identifying genes that can influence human body weight. By focusing on a cohort of children with extreme obesity from an early age, they have discovered a number of gene mutations that lead directly to obesity. Thus far, all of the genes discovered have had their normal function in the hypothalamus, the area of the brain concerned with control of appetite and energy expenditure. These genes have been shown to influence the drive to eat, as well as feeding behaviour. In particular, one genetic defect, though rare, is dramatically curable with a daily injection of a recombinant protein called leptin. This condition is a graphic demonstration that obesity in humans can be purely biologically driven and amenable to mechanism-based therapy. Researchers in the Department of Pharmacology study hypothalamic anatomy and function in an effort to determine how defects in neurocircuitry lead to excess food consumption beyond metabolic need. In particular, hypothalamic neurons – both in isolation and inside their native neural networks – are assessed to explore how they generate their electrical signals, how these signals are communicated to other brain areas, and how they are altered by physiological and pharmacological stimuli.
Brain, nurture, gut flora, and genes
It is now established in animal and human studies that some environmental events can induce long-term developmental changes in chromatin structure through various mechanisms such as histone de-acetylation and DNA methylation of non-coding sequences, which produce long-term silencing of transcription. Since most human brain development occurs postnatally, the brain more than any other organ is under strong social and environmental influences that can have long-lasting effects on brain function and wellbeing.
Nurture should be stronger than nature (genetics) but both affects the person in many ways.