Obesity is becoming a serious global threat nowadays. Combination lack of exercise and regular comsumption of heavy calorie meals are two major factor that people put blame on. However, there is also genetic factor that contribute to obesity, and study in this realm is still inadequate. Study conducted by Lagerlöf in Science (March, 2016) shed light on the depth understanding on the genetic variant as the basic of obesity.
At first, I like to discuss about the current understanding of obesity. In the more details, I would only be focused on the causes of excessive consumption of meals. A hungry signal and innate desire for feeding are actually regulated by brain using input signal generated in stomach, intestine and adipose tissue. Empty stomach releases Ghrelin and stimulate hypothalamus in the brain for creating hungry signal, but the act of two other organs are actually oppose this. Where excessive accumulation of fat tissue produce leptin which will affect hypothalamus to reduce the tendency to eat. The same also goes with intestine, where it secretes PYY in to the bloodstream with stretching of intestine as the indication of fullness. So, normally people should have a homeostatis to regulate the tendency to eat, so the lean mass could be maintained. However, defect in the gene regulate those hormonal regulation have been investigated can cause over-eating and obesity (such as mutation in leptin gene, or gene encode leptin receptor).
Experiment by Lagerlof et. al explains the mechanism occurred in the brain which will regulate the balance of feeding. Using technique so called as genomic analysis, the researcher is able to pinpoint the one of key regulator for food intake. The gene product catalyzed the posttranslational modification of O-GlacNac and is regulated by dietary and metabolic signal from pheriperal organs. Interestingly, the protein acts differently in different area of brain where increase GOT in PVN (periventricular nucleus) associated with hyperphagia (increase feeding intake), but loss of GOT in ARC (Arcuate Nucleus) correlated with impaired adipose metabolism. The exact mechanism of how GOT control those mechanisms has not been elucidated yet, but the experiment was first to describe the critical molecular processes which used as feeding regulator.