Science Bites: Molecule that links smoking to heart disease identified, Mid-life weight gain found linked to enzyme

20170510110000, Vi-Jean Khoo
Science Bites seeks to compile the latest scientific research updates in bite-sized forms.
Science Bites seeks to compile the latest scientific research updates in bite-sized forms.

1. Smoking-related heart disease possibly linked by molecule

Scientists from the Perelman School of Medicine at the University of Pennsylvania and Columbia University have discovered a molecule that links smoking with coronary heart disease (CHD) – an enzyme called ADAMTS7. Excessive production of the enzyme has been linked to the buildup of plaque in coronary arteries.

Though it is normally produced in vascular endothelium, the production of ADAMTS7 was found to increase with smoking. The team analysed DNA data involving over 140,000 individuals from 29 prior studies and identified that a single-letter variant loci on chromosome 15 resulted in a decline in the production of ADAMTS7.

Individuals with the DNA variation were associated with a 12% reduced risk of CHD, but smokers lost most of the apparent protective effect, and had only a 5% reduced risk. Researchers also unveiled that the production of ADMTS7 increased when liquid extract of cigarette smoke was applied to coronary artery-lining cells, supporting the theory that smoking may counteract the genetic protection.

"Findings from this study will hopefully encourage the development of novel therapeutic and preventive programs for CHD, specifically targeting those who smoke," said lead author and assistant professor of Biostatistics and Epidemiology, Danish Saleheen.

2. Scientists discover enzyme linked to mid-life weight gain

Researchers have discovered that an enzyme, DNA-dependent protein kinase (DNA-PK), becomes more active with age – which may explain why the average adult gains roughly 13kg between ages of 20 and 50 years despite reduced food intake.

DNA-PK converts nutrients into fat and reduces the number of mitochondria. Mitochondrial dysfunction has also been linked with a decreased ability to exercise, and low numbers of mitochondria can also lead to obesity.

A 3-D image of the enzyme DNA-PK. Photo credit: Science Daily/ NHLBI
A 3-D image of the enzyme DNA-PK. Photo credit: Science Daily/ NHLBI

The team tested the role of DNA-PK in two groups of mice. While both groups were fed a high-fat diet, one group received a DNA-PK enzyme inhibitor, and was observed to gain 40% less weight than the mice that did not receive the enzyme inhibitor. The DNA-PK enzyme inhibitor also increased aerobic fitness, decreased the rate of obesity and increased the number of mitochondria in the skeletal muscles of mice.

"Our studies indicate that DNA-PK is one of the drivers of the metabolic and fitness decline that occurs during aging, which makes staying lean and physically fit difficult and increases susceptibility to metabolic diseases like diabetes. The identification of this new mechanism is very important for improving public health,” said Dr Jay Chung, lead researcher and head of the National Institutes of Health (NIH) Laboratory of Obesity and Aging Research at the National Heart, Lung, and Blood Institute.

"Our society attributes the weight gain and lack of exercise at midlife... primarily to poor lifestyle choices and lack of willpower, but this study shows that there is a genetic program driven by an overactive enzyme that promotes weight gain and loss of exercise capacity at midlife.”

3. Sex-biased gene expressions linked to differences in men’s and women’s health

Researchers have identified thousands of genes that differ between men and women, which could explain why the two sexes have different disease prevalence or reactions to drugs.

Professor Shmuel Pietrokovski and Dr Moran Gershoni of the Weizmann Institute's Molecular Genetics Department examined roughly 20,000 protein-coding genes in 53 body tissues obtained from 550 individuals to study the differences in expression in each tissue, and identified 6,500 genes that were biased toward one sex or the other.

For instance, genes related to the growth of body hair were highly expressed in the skin of men compared to women. Similarly, gene expression for muscle building was significantly higher in men, while genes for fat storage were higher in women. They also identified a gene that was highly expressed in women’s brains, which may be protective from Parkinson’s disease and explain why the disease is more common in men.

However, the sex-bias genes also tended to accumulate genetic mutations at a higher rate than other genes, possibly because they persist in the population. Genes that affect men’s reproduction, for example, can be passed on by women, who are unaffected by those genes.

"In many species, females can produce only a limited number of offspring while males can, theoretically, father many more; so the species' survival will depend on more viable females in the population than males," Pietrokovski explained. "Thus natural selection can be more 'lax' with the genes that are only harmful to males."

"The basic genome is nearly the same in all of us, but it is utilised differently across the body and among individuals," said Gershoni. "Our results can facilitate the understanding of diverse biological characteristics in the context of sex.” MIMS

Read more:
Science Bites: Phage therapy found effective against bacteria, Protein that protects superbugs from antibiotics identified
Science Bites: 4 biotypes of depression found using fMRI, Fructose conversion in brain linked to neurological problems
Science Bites: Stem cells to treat preemie lungs, Anti-malaria drug boosts treatment for chemotherapy-resistant cancer
The Philadelphia chromosome: The beginning of precision medicine