Obesity: A Gut Reaction to High-Calorie Foods?

A novel study by researchers at Yale University gives new meaning to the term gut reaction. In a series of experiments carried out in rodents, the researchers demonstrate that consuming calorically-dense foods spurs changes in the gut’s microbiome that lead to obesity.

obesity “There have been lots of studies on the association between changes in the microbiome and obesity,” said Gerald Shulman, M.D., the George R. Cowgill Professor of Medicine at Yale University School of Medicine and lead investigator of the report. “This is the first to offer a clear mechanism that explains it.”

After observing in an earlier animal study that acetate, a short-chain fatty acid, stimulates the production of insulin, Dr. Shulman and colleagues undertook the current experiments, published in Nature, which demonstrate that animals fed a high-fat diet displayed higher levels of acetate as well as increased rates of acetate turnover.

In their experiments that followed, the researchers documented a series of events that went something like this: The increased levels of acetate activated the parasympathetic nervous system which in turn boosted secretion of insulin and ghrelin, a hunger-stimulating hormone. That generated a positive feedback loop resulting in increased appetite and, ultimately, a number of metabolic changes associated with obesity including elevated plasma triglyceride levels and fat deposits in muscle tissue and the liver.

“This work provides a very thorough identification of acetate as a ‘postbiotic’ that functions as an important factor in the gut-brain axis,” said biochemist Jonathan Schertzer, Ph.D, assistant professor in the Department of Biochemistry and Biomedical Sciences at McMaster University in Hamilton, Canada. “It also demonstrates acetate’s connection to the regulation of insulin and hormones that contribute to obesity.”

Here’s the thing: The experiments reveal a positive feedback loop that makes sense in the wild. When foraging animals come into contact with foods of high nutritional density, they’re prompted to eat more, because, basically, who knows when the next good meal will come along. But in a world where calorically-dense foods are abundant, that same feedback loop spells trouble. Simply put, the nutrient-gut interaction can promote obesity.

The Effect on Humans

As for what these studies might mean for humans, the researchers say it’s too soon to tell. In the meantime, the U.S. leads the world in obesity, followed by China and India. About 35% or 76.8 million adults in the U.S are obese and about one-third of children and adolescents ages 6 to 19 are obese or overweight, according to the National Institutes of Health. Obesity is linked with a variety of conditions including high blood pressure, heart disease, type 2 diabetes, certain types of cancer including breast and colon, and stroke.

Meanwhile, the human gut microbiome has emerged as a growing subject of study in recent years, in part for its link with obesity. Comprising a complex community of more than 100 trillion microbial cells, the microbiome has been shown to influence a variety of aspects of human health including metabolism, nutrition and immune function.

At the same time, disruption or imbalance of the microbiome has been associated with disorders ranging from gastrointestinal conditions such as irritable bowel syndrome to type 2 diabetes to autoimmune diseases. Both short and long-term dietary change have been shown to influence the composition and function of the diet-sensitive microbiome, and research suggests that infant nutrition may have life-long consequences on the microbiome and its relationship to health.

The recent experiments reveal an actual mechanism at work in the diet-microbiome interplay as it relates to metabolic function and obesity. The researchers say their work identifies a possible therapeutic target for the condition.

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