Overeating Triggers “Master Switch” of Inflammation in Brain

Scientists are finding that obesity is a complex issue, and as they continue to search for clues to its causes, much focus has been placed on a small but vital region of the brain—the hypothalamus. Referred to as the "head ganglion of the autonomic nervous system" by the great Oxford neurophysiologist Sir Charles Sherrington, this almond-sized region of the brain organizes and controls an immense number of bodily functions such as body temperature, circadian cycles, feelings and moods as well as all motivational states including thirst, hunger and appetite, food intake and the body’s energy balance. However, despite some promising studies and experiments involving the hypothalamus, none yet has produced a breakthrough in the obesity battle—until now. Scientists believe they have discovered a “master switch” of inflammation in the hypothalamus that could not only explain overeating and obesity but the “entire family of modern diseases” induced by them.

This “master switch”—called IKK beta/NF kappa B—is usually dormant, but is triggered by overeating. In lab tests on mice, researchers based at the University of Wisconsin-Madison and the University of California, San Diego used “chronic over-nutrition” (essentially a high-fat diet) to turn on the dormant switch. With that master switch turned on, the mice gained weight and became resistant to insulin, which is a hormone that helps convert food into energy and controls blood sugar, and leptin, a hormone involved in regulating appetite. In other mice, the scientists used genetic engineering to turn the switch off. Those mice were “significantly protected” from becoming obese, despite the high-fat diet, the researchers wrote. Although the study was conducted only in mice, the study authors believe the findings will also hold true for humans.

“We discovered a very general disease pathway in the hypothalamus, a structure in the middle part of the brain which functions to regulate appetite, feeding behavior, energy and therefore body-weight balance and metabolic processes,” said Dr. Dongsheng Cai, senior author of the study. “Persistent stimuli from excessive amount of calories can trigger this response before the overt onset of obesity, and this response when induced can promote overeating, contributing to increased levels of caloric overconsumption. So, this process can be like a vicious cycle.”

“The brain is receiving more and more attention from the field…but nobody knows whether and how the hypothalamus could be responsible for the increasing occurrence of energy imbalance and obesity under today’s environment typical of over-nutrition,” Dr. Cai explained. “The first important thing to understand is how the dysregulation of the brain is processed. The study we just did provides a new pathway. It’s the opening of a new direction.”

Dr. Cai said this “pathway” could possibly be used in anti-obesity drugs. “The ultimate goal will certainly be to identify a selective and effective suppressor of the pathway to target related neurons.”

The study findings were published in the October 3 issue of Cell.

http://www.healthnews.com/nutrition-diet/weight-loss/overeating-triggers-master-switch-inflammation-brain-1908.html

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