Although millions of Americans pop fish-oil capsules every day to improve their health, scientists don’t have a clear understanding of how they actually work.
But WID scientists have uncovered an important genetic clue to the answer: the omega-3 fatty acids in the capsules stimulate a protein that in turn suppresses genes involved in certain diseases.
“Right now the scientific community just has correlations between these supplements and health,” says John Denu, scientist in WID’s Epigenetics research area and professor of biomolecular chemistry at the UW School of Medicine and Public Health. “Some people respond to supplements and some people don’t. The more we know about how these fatty acids actually work, the more directed we can be in a therapy or in dietary recommendations.”
Denu is putting “molecular teeth” to understanding how the fatty acids in fish oils make an impact. By focusing on the mechanisms that control gene expression and how metabolism is regulated, Denu hopes to answer questions like how fatty acids help and how we can maximize their benefits.
“The joining of gene expression and metabolism is an emerging area and there are hints that there is a tight link,” said Denu. “In fact, our recent study is an example of highlighting that interconnectedness in a pretty novel and exciting way.”
His recent paper in The Journal of Biological Chemistry links fatty acids to the stimulation of the protein SIRT-6’s activity on chromatin, affecting gene expression by physically manipulating the genome.
Chromatin is the protein-DNA complex that wraps up the genome into a compact structure within cells. But, that tightly spooled DNA is actually in a repressive environment, unable to be translated by the cell to perform tasks. It’s not until proteins are added to the chromatin that a portion of the DNA is unraveled and expressed. The protein SIRT-6 is a repressor, aiding in the repackaging of DNA and halting the over-expression of genes known to promote inflammatory, metabolic-based and age-associated diseases. And with the addition of free fatty acids, they bind to SIRT-6 and make it 35 times more active in repressing its target genes.
SIRT-6 was implicated by an Israeli group of scientists who found that its over-expression caused mice to live longer. A Harvard study subsequently showed that animals without SIRT-6 had profound defects in metabolism, genomic instability, and spontaneously formed cancer.
“The public has heard about omega-3 fatty acids and their potential benefits in terms of cardiovascular disease and cancer. There’s a possibility that this could actually be through a stimulated pathway involving SIRT-6. It makes a lot of sense,” says Denu.
“The public has heard about omega-3 fatty acids and their potential benefits in terms of cardiovascular disease and cancer. There’s a possibility that this could actually be through a stimulated pathway involving SIRT-6.”
— John Denu
For instance, under fasting conditions, there’s an increase in free fatty acids in the body. They’re being liberated from fat cells so the body can burn fat instead of glucose. The body slows down glycolysis (metabolizing glucose) to spare available glucose because it’s the brain’s main energy source. The SIRT-6 protein, Denu believes, might be a key player in responding to those free fatty acids.
“There’s a very strong correlation in human breast-cancer samples and other types of cancers that a loss of this protein is potentially a big deal in terms of tumorigenesis,” says Denu. “A lot of it has to do with SIRT-6’s role in metabolism. Cancer cells are metabolically very distinct from normal cells. They prefer to do glycolysis and don’t want to burn fat. SIRT-6 counteracts what cancer cells like to do, and if you lose that protein, you’re losing that ability.”
“Anyone can buy these things over the counter. Is that really the best? Wouldn’t you want to know a little more about the details? People have heard the positive effects of these things, but the more evidence they hear, the more we all hear, it’s a good thing,” he says. “If we can find a more effective omega-3 or a better way to administer it, maybe you won’t have to eat fish every day.”
— Ian Clark, UW Health