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Omega-3s Show Genetic Benefits
Landmark study adds new reason for the healthful effects of omega-3-rich diets
11/7/2013By Craig Weatherby
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Image The omega-3 story is getting more even more interesting and exciting.

We already know some of the key ways in which omega-3s support optimal health ... see our sidebar, “Omega-3 basics”, below.
 
A new facet of these fish fats is coming into view, thanks to discoveries about the beneficial genetic effects of seafood-source omega-3s.

To help clarify this new chapter of the omega-3 story, we’ll skip over fish to examine one of red grapes’ gene effects.
 
Grapes, wine, and healthy sirtuin proteins
Headlines and high hopes flowed from recent research on resveratrol … an antioxidant in red grapes and wine that brings lab rats metabolic and longevity benefits.

This fruity natural fungicide belongs to the family of broadly beneficial plant-source antioxidants called polyphenols … see “Wine's Anti-Aging Agent May Work in Modest Doses”.

Resveratrol enjoys preliminary evidence of human metabolic benefits, though much more research is needed to detail and confirm them.

But scientists know enough about how it works to be quite confident that resveratrol – like other polyphenols – generally aids human health.

Resveratrol works its apparent metabolic magic by affecting a recently discovered class of proteins called sirtuins.
 
Sirtuin proteins influence genes that control key bodily processes, including aging, inflammation, stress resistance, cancer growth, energy efficiency, circadian rhythms (your biological clock), and more.
Omega-3 basics
The body uses the long-chain omega-3 fatty acids (DHA and EPA) found in all cell membranes for key brain, nerve, and eye cell structures and functions.
 
And they're used to make critical inflammation-regulating messenger chemicals (eicosanoids, resolvins, and protectins).

If necessary, the body can make very small amounts of omega-3 DHA and EPA from the plant-source omega-3 called ALA.

But seafood – and fish/marine oils – are the only food sources of DHA and EPA … the omega-3s we actually need to survive and thrive.)
 
To learn more, see our Omega-3 Facts & Sources page.

Accordingly, scientists view sirtuins as “nutrigenomic” compounds – the term now applied to food chemicals that exert influence over the status of our working genes – which control just about every aspect of health.
 
And over the past several years it’s become apparent that omega-3 fatty acids also exert nutrigenomic effects.

That may sound rather technical but it’s very big news, with major implications for medical research and public health.  
 
Omega-3s stimulate beneficial gene-influencing proteins
Over the past two years, American and Asian research teams reported that omega-3s affect sirtuin proteins in ways that improve vascular health and blood cholesterol profiles while dampening inflammation (Xue B et al. 2012; Inamori T et al. 2013; Jung SB et al. 20123).

Interestingly, Japanese researchers found that people with higher intakes of omega-3s relative to intakes of omega-6 fats from vegetable oils showed beneficial, sirtuin-related, effects on their blood cholesterol profiles (Inamori T et al. 2013).

(Higher omega-3/6 intake ratios are generally beneficial – see “America’s Sickening ‘Omega Imbalance’” and the Omega-3 / Omega-6 Balance section of our news archive – and the Japanese team's finding offers a novel reason why this is true.)

Now, University of Wisconsin scientists report that seafood-source omega-3 DHA and EPA stimulate production of a sirtuin protein that exerts beneficial effects on aging, metabolism, cancer, and inflammation (Feldman JL et al. 2013). 

“Right now the scientific community just has correlations between these supplements and health,” said the lead author, biochemist John Denu, Ph.D. (UWM 2013)

Denu’s team has been trying to reveal how the omega-3s in fish fat impact the “expression” of our working genes:
“The joining of gene expression and metabolism is an emerging area and there are hints that there is a tight link. In fact, our recent study is an example of highlighting that interconnectedness in a pretty novel and exciting way.” (UWM 2013)

The new University of Wisconsin study shows that omega-3 fatty acids stimulate a sirtuin protein called SIRT-6. 

(Recently, Israeli scientists found that “over-expression” of SIRT-6 led mice to live longer … and a subsequent Harvard study showed that animals lacking SIRT-6 suffered spontaneously formed cancers, serious defects in metabolism, and genomic instability.)

Specifically, omega-3s promote SIRT-6’s ability to alter the “expression” of important genes, by physically manipulating the genome.

SIRT-6 does this by acting on chromatin, the protein-DNA complex that wraps up the genome into a compact structure within cells.

Tightly spooled DNA can’t unravel to be “read” by our cells – which would cause them to perform certain tasks – unless specific proteins are added to the chromatin.

By keeping them tightly packed, SIRT-6 helps curb the expression of genes that promote inflammatory, metabolic, and age-associated diseases.

Omega-3 fatty acids bind to and make SIRT-6 about 35 times more active in repressing genes known to promote chronic inflammation and metabolic dysfunctions.

“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,” said Denu.

“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,” he added (UWM 2013).

Dr. Denu noted that their impact on SIRT-6 suggests another reason why omega-3s seem to discourage cancer growth:
“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 [i.e., burn sugar] and don’t want to burn fat. SIRT-6 counteracts what cancer cells like to do ...”. (UWM 2013)

We hope that this study and its recent precedents stimulate more research into the nutrigenomic effects of omega-3 DHA and EPA from seafood.

The more we know, the better able we’ll be to tailor people’s diets to their genetic profiles.
 
As Dr. Denu said, “The more we know about how these fatty acids actually work, the more directed we can be in a therapy or in dietary recommendations.” (UWM 2013)


Sources
  • Borra MT, Smith BC, Denu JM. Mechanism of human SIRT1 activation by resveratrol. J Biol Chem. 2005 Apr 29;280(17):17187-95. Epub 2005 Mar 4.
  • Feldman JL, Baeza J, Denu JM. Activation of the Protein Deacetylase SIRT6 by Long-chain Fatty Acids and Widespread Deacylation by Mammalian Sirtuins. J Biol Chem. 2013 Oct 25;288(43):31350-6. doi: 10.1074/jbc.C113.511261. Epub 2013 Sep 18.
  • Gertz M, Nguyen GT, Fischer F, Suenkel B, Schlicker C, Fränzel B, Tomaschewski J, Aladini F, Becker C, Wolters D, Steegborn C. A molecular mechanism for direct sirtuin activation by resveratrol. PLoS One. 2012;7(11):e49761. doi: 10.1371/journal.pone.0049761. Epub 2012 Nov 21.
  • Inamori T, Goda T, Kasezawa N, Yamakawa-Kobayashi K. The combined effects of genetic variation in the SIRT1 gene and dietary intake of n-3 and n-6 polyunsaturated fatty acids on serum LDL-C and HDL-C levels: a population based study. Lipids Health Dis. 2013 Jan 11;12:4. doi: 10.1186/1476-511X-12-4.
  • Jung SB, Kwon SK, Kwon M, Nagar H, Jeon BH, Irani K, Yoon SH, Kim CS. Docosahexaenoic acid improves vascular function via up-regulation of SIRT1 expression in endothelial cells. Biochem Biophys Res Commun. 2013 Jul 19;437(1):114-9. doi: 10.1016/j.bbrc.2013.06.049. Epub 2013 Jun 24.
  • Pallauf K, Giller K, Huebbe P, Rimbach G. Nutrition and healthy ageing: calorie restriction or polyphenol-rich "MediterrAsian" diet? Oxid Med Cell Longev. 2013;2013:707421. doi: 10.1155/2013/707421. Epub 2013 Aug 28. 
  • University of Wisconsin-Madison (UWM). Fatty Acids Like Omega-3 Play a Role in our Genes. October 30, 2013. Accessed at http://www.med.wisc.edu/news-events/fatty-acids-like-omega-3-play-a-role-in-our-genes/42134
  • Xue B, Yang Z, Wang X, Shi H. Omega-3 polyunsaturated fatty acids antagonize macrophage inflammation via activation of AMPK/SIRT1 pathway. PLoS One. 2012;7(10):e45990. doi: 10.1371/journal.pone.0045990. Epub 2012 Oct 5.
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