It is known that low aerobic fitness is a strong predictor of early death. Now, a University of Missouri researcher has linked low aerobic capacity to a decreased ability to metabolize fat in the liver. Using rats bred over several generations for lower aerobic capacity and decreased ability to metabolize fat, the researchers showed that the rats’ livers are more susceptible to chronic disease, injury and dysfunction later in life. However, despite their genetic predisposition, the study found that exercise lowered the risk factors.

“Fatty liver disease will be the next big metabolic disorder associated with obesity and inactivity,” said John Thyfault, PhD, assistant professor in the MU School of Medicine’s Departments of Internal Medicine and Nutrition and Exercise Physiology. “It also is a significant contributor to type 2 diabetes.”

Low aerobic fitness can partially be linked to genetics but is mainly an end product of physical inactivity. The links between low aerobic fitness and metabolic disease in studies like this highlight the importance of being physically active, which can sustain or improve aerobic fitness across our lifespan, said Thyfault, who also is a health scientist at Harry S. Truman Memorial Veterans Hospital.

In contrast, the same study examined rats that were bred over several generations for high aerobic fitness. Those rats were protected from liver problems. A healthy liver is much better protected from fibrosis, the precursor to non-alcoholic liver cirrhosis. A higher aerobic capacity also means a better functioning heart, lungs, muscles and a lower risk for chronic diseases and early mortality.

“Your personal aerobic fitness is not something you will see in the mirror, but it is an important predictor of your long-term health,” Thyfault said. “The most important part of physical activity is protecting yourself from diseases that can be fatal or play a significant role in increasing the risk factors for other metabolic diseases. Too much fat in the liver also can lead to hyperglycemia.”

Using sedentary rats genetically bred to be low capacity runners allowed researchers to biochemically study the connection between low aerobic capacity and increased fat in the liver. Their main finding was that low aerobic capacity was linked to reduced mitochondrial content and function in the liver, which made the liver more susceptible to fat storage. The researchers believe the rats used in the study mimic the pathology of human chronic metabolic disease better than animal models where single genes are altered.

The study will be published in the Physiological Society’s Journal of Physiology. Jamal Ibdah, MD, PhD, Raymond E. and Vaona H. Peck Chair in Cancer Research and senior associate dean for research in the MU School of Medicine, collaborated on the study.