Levels of liver fat biomarker tied to metabolic benefits of exercise

Last Updated: 2019-06-11

By Marilynn Larkin

NEW YORK (Reuters Health) - High blood levels of the fatty liver disease biomarker dimethylguanidino valeric acid (DMGV) may identify individuals who are less apt to benefit from endurance exercise training, researchers says.

"We were interested in studying DMGV based on prior work by our group that showed that this molecule was a marker of liver fat and that circulating levels were associated with the development of diabetes mellitus over 12 years prior to disease onset," Dr. Robert Gerszten of Beth Israel Deaconess Medical Center in Boston told Reuters Health by email. "We were particularly fascinated by the fact that people who underwent weight loss surgery had decreases in DMGV, and so we wanted to see whether a much more readily available health intervention - exercise - could modulate its levels."

"We found that blood levels of DMGV were associated with unfavorable cholesterol levels, higher levels of visceral fat, and abnormal regulation of insulin and glucose in a group of people with normal weight and without cardiovascular problems," he said.

"While people from this study were able to decrease their levels of this chemical after exercise training, individuals with higher levels of DMGV prior to exercising experienced lesser benefits in terms of their good cholesterol levels and insulin sensitivity after participating in this exercise study," he said. "This finding supports the notion that individuals respond differently to exercise."

Dr. Gerszten and colleagues analyzed plasma samples collected before and after exercise training from participants in the the Health, Risk Factors, Exercise Training, and Genetics (HERITAGE) Family Study, a 20-week, single-arm endurance exercise clinical trial performed in multiple centers between 1993 and 1997.

As reported online June 5 in JAMA Cardiology, participants' mean age was 36, 52% were women, all were white, and the median body mass index was 25.

After adjustment for age and sex, baseline levels of DMGV were positively associated with body fat percentage, abdominal visceral fat, very low-density lipoprotein cholesterol, and triglycerides. By contrast, the levels were inversely associated with insulin sensitivity, low-density lipoprotein cholesterol levels, high-density lipoprotein size, and high-density lipoprotein cholesterol levels.

After further adjustment for baseline traits, baseline DMGV levels after exercise training were positively associated with changes in small high-density lipoprotein particles and inversely associated with changes in medium and total high-density lipoprotein particles, apolipoprotein, and insulin sensitivity.

The authors conclude that DMGV "is an early marker of cardiometabolic dysfunction that is associated with attenuated improvements in lipid traits and insulin sensitivity after exercise training," and might be used to identify individuals less responsive to the health benefits of endurance training.

"Our study raises questions about the role that this molecule plays in cholesterol and fat metabolism," Dr. Gerszten said. "To answer these questions, we have to study its mechanistic role in cells and animal models. That work is already underway in our lab."

"The next steps are expanding the populations (beyond white) that we study, (using) different exercise modalities - e.g., resistance training - and expanding this line of research to additional technologies such as genetics and protein profiling," he concluded.

Dr. Sean Heffron, a cardiologist and assistant professor of medicine at NYU Langone Health in New York City, commented by email, "This marker appears to be associated with early cardiometabolic disease as measured by a number of glucose homeostasis and lipid measures. Changes in serum lipoprotein characteristics with exercise training also appear to be related to pre-training levels of DMGV."

"However, the clinical relevance of the lipoprotein changes - predominantly related to HDL - that the investigators measure are far from clear," he told Reuters Health. "Additionally, there is no evidence that DMGV is at all causative in changes associated with exercise. It may turn out to be, but all data to this point are completely correlative."

"Identifying individuals at risk for cardiometabolic disease as early as possible is a very important goal," he acknowledged. "However, whether DMGV is appropriate for this will require validation in far more people."

SOURCE: http://bit.ly/2WZJhT9

JAMA Cardiol 2019.