Familial risk factors for being very overweight show up in the brain at an early stage, a new study shows. According to this, the brain metabolism of people with a family history is changed in such a way that the feeling of satiety and appetite are less regulated. The reasons for this are a reduced function of the opioid and cannabinoid systems in the brain as well as deviating reactions to insulin. These effects can be seen even before a person has actually developed obesity. According to the researchers, the findings could help develop new treatment and prevention strategies against obesity and diabetes.
Obesity is a growing health problem around the world. Being very overweight increases the risk of numerous diseases, including cardiovascular diseases, cancer and type 2 diabetes. It is already known that the appetite regulation in the brain is disturbed in obese people. While insulin usually creates a feeling of satiety in the brain, this function is reduced in severely overweight people – and causes excessive calorie intake. In addition, obese people show changes in the reward system, in which the body’s own opioids and cannabinoids are involved. Obese people have fewer receptors for these reward messengers.
How the brain metabolism makes you hungry
“Until now, however, it was unclear whether these changes in the brain are already visible before a person develops obesity and whether these changes increase the risk of future obesity,” says Tatu Kantonen from the University of Turku in Finland. Together with his colleagues, he has now investigated this question. To do this, the researchers measured the effects of insulin as well as the body’s own opioids and cannabinoids in the brain in 41 men between the ages of 20 and 35. Twenty-two of the test subjects examined regularly played sports, had no cases of obesity or type 2 diabetes in their parents, a low to medium body weight and thus a low risk of obesity. Nineteen subjects were slightly overweight, had parents with overweight or type 2 diabetes, seldom physical activity and were thus at high risk of obesity.
With the help of positron emission tomography (PET), the researchers first investigated how glucose is distributed in the subjects’ brains – a measure of insulin activity. In addition, they recorded how many receptors for opioids and cannabinoids were present. The comparison between the two groups revealed: “Young men at high risk of future obesity had an increased insulin-stimulated glucose uptake in the brain,” said the researchers. This was particularly evident in regions that are responsible for the feeling of hunger, such as the hypothalamus and the insula.
Dysfunctional reward system
“Disruptions to the action of insulin in the brain and impaired signal transmission between the brain and peripheral organs can contribute to pathological dysregulation of the energy balance and to weight gain,” the researchers explain. This effect was already known from people with pronounced obesity. “Our results show that these pathophysiological processes are already active in non-obese people with risk factors for obesity,” the researchers say.
They also found that an increased familial risk of obesity was associated with a lower density of receptors for opioids and cannabinoids. Similar patterns have been seen in those with obesity and binge eating disorder. “Previous studies have shown that downregulating opioid receptors makes people more sensitive to rewarding food stimuli in the environment,” explain the cantons and his colleagues. “People with a hereditary predisposition for downregulated opioid receptors could therefore react more sensitively to food stimuli in the environment, which leads to excessive food intake.” Alternatively, it is conceivable that people with fewer opioid receptors eat more in order to induce a sufficient reward reaction that is sufficient for them Cease food intake.
New starting points for preventive measures
“Disturbances in the neural networks that control satiety and appetite can therefore be observed even before a person develops obesity, and these brain changes are linked to familial risk factors for obesity,” says Kantonen. “The results could have implications for the development of obesity prevention and treatment interventions. They show that the brain and central nervous system are important targets in the treatment of obesity. “
Source: Tatu Cantons (University of Turku, Finland) et al., International Journal of Obesity, doi: 10.1038 / s41366-021-00996-y