Are people who love cuts of prime rib and potatoes smothered in butter bombarding their intestines and skeletal muscles with too much fat?

Virginia Tech scientists are launching an in-depth research investigation to better understand the effects of a high-fat diet on skeletal muscle metabolism in the human body.

Previous studies in mice show that high fat diets lead to modest but chronic elevations of bad bacterial byproducts in the blood called endotoxins. Produced from bacteria in the digestive track, endotoxin leaks into the blood stream through the intestine.

Modest elevation in blood endotoxin can be problematic because it can disrupt normal skeletal muscle metabolism, which is a risk factor for development of obesity, metabolic syndrome, and type 2 diabetes. 

Now, researchers are studying this interplay in the human body, with the help of a $600,000 grant from the American Diabetes Association.

"Our study will address a gap in the literature," said Matthew Hulver, associate professor of human nutrition, foods and exercise in the College of Agriculture and Life Sciences and an affiliated researcher with the Fralin Life Science Institute. "We know that obesity and type 2 diabetes are associated with elevated levels of blood endotoxin and abnormal skeletal muscle metabolism, but it has not been confirmed in humans that a high fat diet alters the integrity of the intestines and causes metabolic endotoxemia, which we hypothesize will cause abnormal metabolism in skeletal muscle."

For the next three years, Hulver; along with Brenda Davy, an associate professor of human nutrition, foods and exercise; Kevin Davy, a professor of human nutrition, foods and exercise; and Andrew Neilson, an assistant professor of food science and technology, all in the College of Agriculture and Life Sciences, will conduct a research project in which groups of healthy men, aged 18-40 will consume a high fat diet for five days and be assessed for intestinal permeability, blood endotoxin, and skeletal muscle metabolic function. 

Ultimately, the researchers are looking for signs of metabolic inflexibility — the inability of skeletal muscle to adapt fuel oxidation to fuel availability, which is a hallmark feature of obesity and other metabolic disorders.

"We have been able to show in preliminary studies with healthy men that skeletal muscle becomes less metabolically flexible and blood endotoxin levels are increased in response to only five days of high fat feedings," Hulver said. "If we can confirm this in a larger pool of subjects, this will provide the first evidence in humans that short-term high fat feeding disrupts the intestinal barrier and normal skeletal metabolic flexibility. This could lead to the development of interventions that may be used to prevent the deleterious effects of high fat feeding that contributes to the progression of metabolic diseases such as obesity and type 2 diabetes."  

Hulver, Davy, Davy, and Neilson are all affiliated with the Fralin Translational Obesity Research Center, established in January with the aim to improve health and quality of life in the Commonwealth of Virginia and the nation. More than one-third of adults in the United States and about 17 percent of the nation's children are obese, increasing their risk for type 2 diabetes, heart disease, stroke, liver disease, and some cancers, according to the National Institutes of Health.



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