Researchers Find New Pathway Linked to Obesity

New research published in the October issue of the journal Cell suggests overeating activates a metabolic response usually inactive in hypothalamus - middle region of the brain - contributing to increased levels of caloric consumption.

Researchers examined pathways that contribute to obesity. They investigated “metabolic inflammation,” a chronic, low-level condition often seen in obesity related illnesses.

The research focused on the “master switch” of inflammation, called IKKbeta/NF-kB that is usually inactive.

“The IKKb/NF-kB pathway in the hypothalamus region of the brain, functions to stabilize appetite, thirst, energy, fatigue, body temperature and metabolic processes,” said Dr. Dongsheng Cai, MD, PhD, senior author of the study and an assistant professor of physiology at the University of Wisconsin-Madison.

Continuous stimuli from extreme calorie intake can activate this response before the onset of obesity. When triggered, this response can promote overeating, contributing to greater levels of caloric overconsumption, he added. “It’s a vicious ongoing cycle.”

Two-thirds of U.S. adults are considered overweight or obese. A recent study in the journal of Obesity says all American adults may become overweight in forty years if the current weight trends continue unchanged.

Overweight and obese individuals are at increased risk for many diseases and health conditions such as high blood pressure, osteoarthritis, high cholesterol, Type 2 diabetes, coronary heart disease, stroke, gallbladder disease, sleep apnea and respiratory problems, and even some cancers.

Until now, researchers did not know that the hypothalamus region of the brain was essential for how energy is processed in the body.

Earlier research has found that overeating triggers inflammatory responses in the muscles and other metabolic tissues - changes that underlie Type II diabetes development. So, the IKKB/NF-kB pathway has already been marked as a critical part of these processes.

But, until now, researchers were unsure if the same pathway was also involved in the central nervous system.

While examinging the brains of mice, researchers discovered diets high-in-fat or high-in-sugar increased the activity of this pathway in the brain. Similarly, the pathway was active in the mice predisposed to obesity.

When triggered, the pathway induces insulin resistance and dysfunctions of other hormones engaged with appetite and weight control.

While researchers have always thought chronic inflammation to be the result of obesity, they now believe it also promotes it. Suppressing this pathway may be a new strategy in the battle against obesity and associated health issues. The pathway could possibly be used in new anti-obesity drugs, Dr. Cai said.

A recent study in the New England Journal of Medicine, suggests adults and children who excessively overeat may be missing a gene for a brain chemical that is needed for appetite control.

The study, conducted by National Institutes of Health (NIH), involved 33 adults and children with WAGR syndrome, a rare disorder in which clusters of genes are deleted. Researchers examined the correlation between genotype and body-mass index (BMI). #