“When we talk about weight gain and obesity, suddenly the concept of choice, the concept of willpower, appears. But is it a choice? No, I don’t think it is a choice and I hope you will agree with me at the end of the lecture,” said Prof. Giles Yeo. He emphasized that our eating behaviors and how much we weigh are determined not only by culture, but also by biology."
Leptin-melanocortin pathway
Prof. Yeo emphasized that it plays a key role in the control of the hypothalamus in food intake and control and regulation of appetite.
“What do we know about the human species?” asked the speaker. “The biological trend is that as a species we are maturing earlier, becoming taller and fatter. Regardless of population or ethnic group. We believe that this is, to some extent, caused by disturbances in the leptin-melanocortin pathway.”
The speaker presented severe mutations in the genes of this pathway, which result in excessive hunger. He was the first to describe a case of leptin deficiency, then he focused on mutations occurring in the melanocortin-4 receptor (MC4R) gene and on proopiomelanocortin (POMC) deficiency. These mutations are a very rare, although most common monogenic cause of severe obesity in humans – a person with the MC4R mutation has on average 25% more body weight than a person without the mutation. This shows how much our biology influences how much we weigh.
Polygenic cause of obesity in humans
While the examples discussed at the very beginning were related to a mutation in one gene, they concern only 0.3% of the human population. In 99.7% of people around the world, the cause of obesity is polygenic: how much fat we have is related to genes working in the brain that influence our eating behaviors. There are now at least 1,000 known loci (specific areas in chromosomes occupied by genes) that are linked to how we eat.
“Even subtle changes in genes affect our place on the weight distribution chart,” said Prof. Giles Yeo. “The more risk factors, i.e. changes in these genes, you have the more likely you are to be obese.”
There is always room for dessert
Why? The explanation is related to evolution and goes back several dozen thousand years:
If our ancestors 50,000 years ago needed 2,000 calories to hunt an antelope, then after hunting it they had to eat 2,000 calories to make up for this energy expenditure,” explained Prof. Yeo. “But without knowing whether it would be possible to hunt something again the next time, once full, the brain turned on its pleasure part, starting to crave for higher-calorie foods: fatty and sweet. What meal has both of these ingredients? Of course, dessert. I understand that dessert is a socio-cultural construct,” – said Prof. Yeo. “But the phenomenon of craving for calorie-dense food when a person becomes full is preserved through evolution. So where is the choice?”
Is obesity a choice?
Finally, the speaker emphasized that, as a geneticist who talks about the mechanisms of obesity, he does not give people with obesity an excuse. However, there are people for whom losing weight is more difficult. It is not a matter of their bad will or laziness, but a struggle against biology. Only when we realize this, we will be able to help fight the problem of excess weight.
The lecture took place on April 4. It was organized as part of the “STER Internationalization of Doctoral Schools” program of the National Agency for Academic Exchange.