Researchers at the University of Gothenburg, Sweden, have clarified the link between the molecule interleukin-6 (IL-6) in the brain and obesity. In experiments on rats and mice, they show that the molecule does affect the risk of obesity; and also where this effect occurs in the brain.
Interleukin-6 (IL-6) is a well-known pro-inflammatory molecule; and an integral element of body’s first line of defense during infection. Intriguingly, the brain may govern and utilize IL-6 differently from the rest of the body. Researchers led by the laboratory of Karolina Skibicka at the Sahlgrenska Academy; Sweden wondered what happens to IL-6 levels in the brain following a diet that leads to obesity.
Rats and mice were offer a high-calorie palatable food, a mix of fat and sugar; in addition to their regular low-calorie diet. Like many humans, rodents choose to overeat when presented with calorie-dense foods.
Lateral parabrachial nucleus
“What we found was that the rats and mice that became obese had reduced IL-6; but only in one brain region called the lateral parabrachial nucleus (lPBN)”; says Devesh Mishra, postdoctoral fellow leading the study. “To understand whether this reduction of IL-6 is a good or bad thing for the metabolic health of the rodents; but we viro-genetically reduced IL-6 levels very selectively in the lPBN; this led to increased body weight and body fat, even in rodents fed a healthy diet.”
Therefore, the researchers have concluded that the reduced levels of lPBN IL-6; in obesity are problematic, and likely contribute to metabolic dysfunction and weight gain. Since body weight is a result of the amount of food consume, i.e., energy intake; versus how much energy we use, i.e. energy expenditure, weight gain can follow dysfunction of either one of these branches of energy balance.
What makes local parabrachial nucleus-produced IL-6 extra important, the study found; is that it affects both branches simultaneously. It decreases food intake and increases energy expenditure, the latter by increasing brown fat activity; so body’s energy is utilize for heat generation or fat burning. Hence, reduced levels of lPBN IL-6 disrupt the entire energy balance equation.
Obese and overweight men
These findings may be relevant not only for mice but also men; since an earlier study from University of Gothenburg revealed that blood serum IL-6 levels; in obese and overweight men are increase, yet brain IL-6 levels measure in cerebrospinal fluid are reduce.
There is one unresolved issue relate to these findings researchers found that the obesity-associate reduction in IL-6; was only present in males. Female rats and mice had normal IL-6 levels. The Sahlgrenska team is now investigating why females are protected from the obesity-associated IL-6-driven dysfunction.
Given that obesity is a major global disorder with 1.9 billion overweight individuals; out of which 650 million are obese, effective anti-obesity treatments are desperately needed to minimize the amount of personal and medical burden on individuals and societies. On the scientific end, researchers think that IL-6 as a satiety-mediating substance with brain region specificity is an important discovery, and can open new directions in the quest for more effective anti-obesity strategies.