DNA link to sugar impact risk for heart disease and diabetes
Genes in mitochondria, the “powerhouses” that turn sugar into energy in human cells, shape a person’s risk for heart disease and diabetes, according to a study from researchers at the University of Alabama at Birmingham (UAB).
The findings may have implications for diet-planning and the ongoing debates surrounding added sugars in foods and beverages.
Researchers said the findings, published in the Biochemical Journal 8 August 2013, may explain why some people get sick and others do not despite having the same traditional risk factors like ageing, obesity and smoking.
Research in recent years has shown that miscues in mitochondrial energy production create too many particles called oxidants and free radicals that cause cells to self-destruct as part of heart disease, diabetes and cancer.
“Having been in this field for decades, I remember when mitochondrial DNA variations were thought to play a role only in the rarest of genetic syndromes,” said Scott Ballinger, PhD, Professor in the Division of Molecular and Cellular Pathology at the UAB School of Medicine and corresponding study author. “Today there is a growing consensus that variation in mitochondrial DNA alone make a substantial contribution to each person’s risk for heart disease, and ours is the first study to directly confirm it in a living mammal,” he said.
Evolution of mitochondria in humans
The UAB study reflects the theory that humans’ ancient one-celled ancestors “swallowed” the bacterial forebears of what are now mitochondria. These gave their hosts the ability to convert sugar from food into about 15 times as much cellular energy as the hosts could by using oxygen. As the evolutionary process continued, the mitochondria became permanent sub-compartments of human cells.
Each human cell has two genomes, the long stretches of DNA that encode the blueprint for the human body: one set inherited from both parents in a central nucleus, and a separate, smaller set in each mitochondrion. The mitochondria genes are inherited from a child’s mother.
Researchers have struggled to genetically engineer mice that would enable them to separate the impact of one gene set from the other, making the theory that mitochondria DNA shape disease risk difficult to prove. Additionally, the human nuclear genome contains more than 30,000 genes, compared to just 13 energy-related genes in the mitochondria.
To determine whether mitochondrial DNA variations contributed to disease risk independent of an individual’s nuclear DNA, the UAB research team swapped the mitochondria of two different varieties of mice.
The C57 mouse is known to be vulnerable to diseases associated with diet, where the C3H mouse is known to be resistant to such diseases. The researchers used a technique called nuclear transfer to remove the nucleus from an embryo in each mouse variety and swap them. The embryos with switched nuclei grew into mice whose cells had their own mitochondrial DNA and the nuclear DNA from the other mouse variety. This enabled the researchers to isolate the mitochondria DNA’s contribution of disease risk by comparing mice with the same nuclear DNA but different mitochondrial DNA.
Findings showed increased risk for heart disease
The findings showed a major contribution of the mitochondria DNA from the C57 mice to the susceptibility to the pathological stress of cardiac volume overload, independent of the nuclear DNA.
Additionally, the research showed that putting disease-vulnverable C57 mitochondria in a cell with a C3H nucleus made that cell take on the energy characteristics of the original, more energy efficient C57 strain. This decreased the amount of oxygen needed to make the same amount of energy by 15 per cent. Mice with C57 mitchondrial DNA also generated 200 per cent more oxidants than their disease-resistant counterparts with C3H mitochondrial DNA.
“We propose this is the primary mechanism associated with increased bioenergetic dysfunction in response to volume overload,” the study’s authors wrote.
Support for the research was provided by the National Institutes of Health, the National Foundation for Cancer Research, the Susan G. Komen Foundation, US Army Medical Research and Material Command, and a pilot grant from the UAB Comprehensive Cancer Centre. Additional support came from the American Heart Association and the NIH-funded Diabetes Research Centre’s Bioanalytical Redox Biology Core located at the University of Alabama at Birmingham. The technology used is the subject of a pending patent application filed on the intellectual property rights owned by The UAB Research Foundation.