Chronic Lactate Exposure Disrupts Cellular Metabolism

Researchers in Colorado have found that chronic exposure to lactate—a byproduct of glucose that accumulates in cells during exercise—can actually cause cellular disruptions that lead to cancer, heart failure and type 2 diabetes.

Lactate is a major source of energy for the cell, especially the mitochondria, and is a preferred fuel over glucose in the heart, muscles and the brain. It is also produced during exercise and rapidly cleared from the body through the mitochondria, which swiftly oxidizes it.

However, scientists at University of Colorado Anschutz Medical Campus have found that when rats were exposed to lactate for up to 48 hours, they became more susceptible to disease.

“We know that lactate is not just a waste product,” says lead author Iñigo San Millán, PhD, assistant professor at the University of Colorado School of Medicine and associate professor at the University of Colorado, Colorado Springs. “It has significant signaling and regulation properties at the cellular level.” When acutely exposed to cells, like during exercise, lactate is beneficial, but chronic exposure “disrupts cellular metabolism entirely,” he adds.  

The researchers focused on whether chronic lactate exposure could decrease the activity of cardiac mitochondria, cause cellular disruption and lead to metabolic inflexibility of the heart. They discovered that long-term lactate exposure led to a significant decrease in fatty acid transport, alterations of a key component in mitochondrial membranes known as cardiolipin, and decreases in mitochondrial ATP or energy production. It also prompted increases in free radicals that could cause heart failure and play a role in type 2 diabetes.

“We found that dysregulated lactate is probably a major player in disease,” San Millán said. “This is a rat model but we believe the results would be similar in human cells.”

In a previous study, San Millán and colleagues showed that lactate could be a master regulator of carcinogenesis—the process that turns a normal cell into a cancer cell. “Cancer cells are producing glucose all the time and they are producing lactate all the time and it is never cleared out like it is during exercise,” he said. “This lactate accumulation regulates the expression of many key genes involved in cancer as we have recently shown.”

The next step is determining the mechanisms involved in the decreased ability to clear lactate. “We believe that a primary mitochondrial impairment or dysfunction could lead to excessive lactate accumulation leading to disease,” says San Millán, who is also Director of Performance for UAE Emirates Cycling Team. “And right now, the only medication we have to fix mitochondrial function is exercise.”

The study was published recently in Frontiers in Nutrition.