Brain mechanism regulates body weight, study says

Chronic low-grade inflammation and increased serum levels of the cytokine interleukine-6 (IL-6) accompany obesity, but for brain-produced IL-6, the mechanisms by which it controls energy balance and its role in obesity remain unclear. A new study by researchers at the University of Gothenburg in Sweden clarify the link between IL-6 in the brain and obesity, according to a new study published in the journal Cell Reports.

The researchers conducted experiments on rats and mice, which were offered 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, researchers said.

As the rats and mice became obese, the researchers found they had reduce IL-6 only in the Lateral Parabrachial Nucleus (lPBN) region of the brain. To understand whether the reduction of IL-6 was a good or bad thing for the metabolic health of the rodents, they viro-genetically reduced IL-6 levels selectively in the lPBN. This led to increased body weight and body fat, even in rodents fed a healthy diet.

Interleukine-6 (IL-6) is a well-known pro-inflammatory molecule, and an integral element of body's first line of defense during infection. The brain may govern and utilize IL-6 differently from the rest of the body, researchers say.

 The researchers 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 how much we eat, energy intake and how much energy we use, 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 the body's energy is utilized for heat generation or fat burning. Hence reduced levels of lPBN IL-6 disrupt the entire energy balance equation, researchers said.

Researchers did find the obesity-associated reduction in IL-6 was only present in males. Female rats and mice had normal IL-6 levels. The 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, according to the World Health Organization, new effective anti-obesity treatment is needed to minimize the amount of personal and medical burden. On the scientific end, researchers say that IL-6 as a satiety mediating substance with a brain region specificity is an important discovery and can open new directions in the quest for more effective anti-obesity strategies.