Clearly, even in the “obesogenic” environment we live in today (which encourages weight gain), there is a wide variation in body weight. Much of this is due to genetics.
Most of the evidence for the genetic basis of body weight comes from twin studies, which have found that the heritability of weight varies between 40% and 70%.
Additionally, the genetics of body weight reveal how the brain influences our desire to eat – in other words, appetite.
Appetite regulation is surprisingly complex because it involves three basic concepts: hunger, satiety, and reward, each regulated by different parts of the brain.
Hunger is controlled by the hypothalamus, satiety is controlled primarily by the hindbrain (the area near where the head meets the neck), and reward is controlled by a diffuse upper region of the brain (the “hedonic area”). These parts of the brain are interconnected and “talk” to each other.
The brain also needs two types of information to influence appetite. First, it needs to know how much fat you have, and second, it needs to know how much you’ve eaten and that you’ve just eaten. Both of these signals are hormonal. That is, they’re released into the bloodstream and eventually transmitted to the brain.
More than 1,000 genes have now been discovered that affect body mass index (BMI). These include genes for many components of the melanocortin pathway, including POMC and MC4R, which regulate food intake. In people with genetic variations in this key pathway, the brain thinks there is less fat in the body than there actually is. This increases hunger, causing people to eat more. There is now a drug called setmelanotide (from Rhythm Pharmaceuticals) that targets this system. It is currently being tested in people with MC4R deficiency.
Of the 20 gut hormones we know of, 18 help us feel full. In general, foods that take longer to digest pass through the intestines more, leading to changes in the gut’s hormonal repertoire. This increases the feeling of fullness.
A key gut hormone that increases significantly after eating and is particularly sensitive to protein is GLP-1. A whole new class of anti-obesity drugs, such as Ozempic and Wegovy, focus on modified versions of this hormone. These drugs make you feel full, making it easier to lose weight.
Socioeconomic status plays a major role in whether a person becomes obese. One study found that if a person is genetically predisposed to obesity, living in a healthy environment can more than halve that risk.
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Source: Ferra
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