UW Researchers Offer Hope for the Prevention and Treatment of Obesity

University of Wisconsin-Madison researchers, for the first time, have found a messaging system in the brain that directly affects food intake and body weight.

Findings from a study in mice point to a completely new approach to treating and preventing obesity in humans. The discovery also offers hope for new ways to treat related disorders, such as type 2 diabetes and cardiovascular diseases — the most prevalent health problems in the United States and the rest of the developed world.

Led by Dongsheng Cai, MD, PhD, an assistant professor of physiology at the UW School of Medicine and Public Health, researchers looked specifically at the hypothalamus — the brain structure responsible for maintaining a steady state in the body — and for the first time found that a cell-signaling pathway, primarily associated with inflammation, also influences regulation of food intake.
Stimulating the pathway led to energy over-consumption by the animals, while suppressing it helped them maintain normal food intake and body weight.

The research stems from recent explorations into a problem called metabolic inflammation, a byproduct of too much food or energy consumption.

"Unlike the type of inflammation associated with infections, injuries and diseases such as cancer, metabolic inflammation is a chronic, low-grade condition that occurs at the molecular level, and has many negative consequences," says Cai. "By disrupting cellular function, it can hinder regulation of crucial physiological processes such as metabolism."

Scientists believe that metabolic inflammation may be at the core of many chronic, obesity-related metabolic disorders that are common today.

In the current study, Cai and his team have investigated a specific gene and protein associated with these complex processes and have shown that over-nutrition through feeding mice a high-fat diet does indeed activate metabolic inflammation in the neurons of the hypothalamus.

Cai cautions there's still a lot of work to be done. "The ultimate goal will be to identify a selective and effective way to suppress the nervous system pathway to target affected neurons," he says.

Meanwhile Cai continues to look at the big picture, seeking answers to questions such as "What are the key steps that have led to the dramatic rise of diabetes in the past three decades? How does the environment connect to the genetics that seem to underlie the obesity epidemic? And why can't the body adjust to changes in the way people eat and what they eat?"