Discovery of new brain mechanisms that regulate body weight

Obesity is a global health-threatening disease. According to statistics, there are more than 1.9 billion overweight individuals, about one-third of whom are obese. Obesity hides the potential risks of many diseases, so effective anti-obesity treatments are urgently needed.

It is well known that interleukin-6 (IL6) is a pro-inflammatory molecule that is part of the innate immune system. However, researchers at the University of Gothenburg in Sweden have discovered a link between IL6 in the brain and obesity. Through experiments in rats and mice, they confirmed that IL6 does affect the risk of obesity and where this effect occurs in the brain.

Interestingly, the brain's control and utilization of IL6 may be different from other parts of the body. The researchers wanted to know what happens to the level of IL6 in the brain after a diet that causes obesity.

During the experiment, the researchers fed rats and mice with high-calorie foods such as fat and hot mixture. These rodents, like humans, choose to eat too much when they eat high-calorie foods.

They found that IL6 was reduced in obese rats and mice, but only in a region of the brain called the parabrachial nucleus (lPBN).

To explore whether the reduction in IL6 is good or bad for the metabolic health of rodents, the team has very selectively reduced the level of IL6 in lPBN by viral inheritance. The result is that even for rodents with a healthy diet, their weight and fat increase.

Therefore, the researchers believed that a decrease in lPBN IL6 levels in obesity may lead to metabolic dysfunction and weight gain. Since body weight is the result of energy intake and energy expenditure, any dysfunctionality in either of the two branches of energy balance results in weight gain.

After further research, the team found that IL6 produced by the parabrachial nucleus affects both branches, namely, it reduces food intake and increases energy expenditure, while the latter increases brown fat activity, so the body's energy is used to generate heat or burn fat. Therefore, lowering the IL6 level in lPBN breaks the entire energy balance.

Early studies at the University of Gothenburg have shown that serum IL6 levels in obese and overweight men are elevated but brain IL6 levels measured in cerebrospinal fluid are reduced. So these findings apply not only to mice but also to men.

The researchers also found that the reduction in IL6 associated with obesity was only found in men. Female rats and mice have normal IL6 levels. The research team is now investigating why women are immune to obesity-related IL6-driven dysfunction.

The discovery of IL6 as a brain-specific satiety substance is an important finding that opens up new directions for more effective anti-obesity strategies.