A new study confirms that familial risk factors for obesity appear in the brain at an early stage. Consequently, the metabolism of the brain in people with a family history changes in such a way that feelings of satiety and appetite are less regulated. This is due to decreased function of the brain’s opioid and cannabinoid systems and an abnormal insulin response. These effects are visible before a person actually develops obesity. According to the researchers, the findings could lead to the development of new strategies for treating and preventing obesity and diabetes.
Obesity is a growing health problem all over the world. Being overweight increases the risk of many diseases, including cardiovascular disease, cancer and type 2 diabetes. It is already known that the regulation of appetite in the brain of obese people is impaired. While insulin in the brain usually makes you feel full, this function is diminished in people who are heavily overweight – and it causes an excessive intake of calories. In addition, obese people show changes in the reward system, which includes endogenous opioids and cannabinoids. Those who suffer from obesity have fewer receptors for these reward neurotransmitters.
How the metabolism of the brain makes you hungry
“However, it was previously unclear whether these changes were already visible in the brain before a person develops obesity, and whether these changes increase the risk of future obesity,” says Tatu Kantonen of the University of Turku in Finland. He and his colleagues were now investigating the issue. To do this, researchers measured the effects of insulin and endogenous opioids and cannabinoids on the brains of 41 men aged 20 to 35 years. Twenty-two of the subjects exercised regularly, had no overweight or type 2 diabetes in their parents’ home, had a low or moderate body weight and therefore had a low risk of obesity. Nineteen of the subjects were slightly overweight, had parents with obesity or type 2 diabetes, had rarely exercised and therefore were at high risk of obesity.
Using positron emission tomography (PET), the researchers first studied the distribution of glucose in their brains – a measure of insulin activity. In addition, they measured the number of opioid and cannabinoid receptors present. A comparison between the two groups revealed: “Young men at high risk of future obesity had increased insulin-stimulated glucose uptake in the brain,” the researchers said. This was especially true in hungry regions such as the hypothalamus and the island.
Disrupted reward system
“Disrupted insulin action in the brain and disrupted signal transmission between the brain and peripheral organs can contribute to pathological dysregulation of energy balance and weight gain,” the researchers explain. This effect was already known to people with severe obesity. “Our results show that these pathophysiological processes are already active in non-obese people with obesity risk factors,” the researchers say.
They also found that an increased family risk of obesity was associated with a lower density of opioid and cannabinoid receptors. Similar patterns have been found in people with obesity and eating disorders. “Previous studies have shown that downregulation of opioid receptors makes individuals more sensitive to rewarding food stimuli in the environment,” explains Cantonen and his colleagues. “People with a hereditary predisposition to lower opioid levels may therefore respond more sensitively to environmental food stimuli, leading to overeating.” stop eating them.
New starting points for preventive measures
“So, disruptions in the neural networks that control satiety and appetite can be seen before a person develops obesity, and these brain changes are associated with family risk factors for obesity,” says Cantonen. “The results may influence the development of interventions in the prevention and treatment of obesity. They show that the brain and central nervous system are important targets in the treatment of obesity. ‘
Source: Tatu Kantonen (University of Turku, Finland) et al., International Journal of Obesity, doi: 10.1038 / s41366-021-00996-y