Townsend finds mice fed foods rich in omega-3 polyunsaturated fats sustain tissue damage

Some people trying to eat healthy increase their consumption of salmon, tuna or mackerel — foods rich in omega-3 polyunsaturated fats (n-3 PUFA).

People also take fish oil supplements that boost intake of vitamin D for healthy bones and muscle, and to regulate the release of serotonin, which affects appetite and stress.

And why not? The prevailing nutritional narrative is that diets that include omega-3 fatty acids and fish oil supplements are metabolically healthy, says Kristy Townsend.

But the University of Maine neurobiologist demonstrated, for the first time, that while young mice on an n-3 PUFA diet had a striking reduction in weight gain, they also sustained adipose, or fat, tissue damage and dysfunction.

That’s because the n-3 PUFAs had undergone peroxidation, a process of nonenzymatic degradation that produces toxic fatty acid byproducts.

Regardless of the source of the n-3 PUFAs, including tinned fish and fish oil supplements, as well as attempts to mitigate the process of peroxidation, Townsend found most sources contained high levels of potentially harmful peroxidized lipids.

These findings potentially have important implications for human nutrition and dietary health, says the associate professor of neurobiology.

Since the brain is second only to adipose tissue (fat, or loose connective tissue that stores energy and cushions and insulates the body) in terms of fat/lipid content, it’s important to understand how dietary fats affect brain and adipose lipid metabolites — small molecules involved in metabolism — and their cellular functions.

The types of tissue damage Townsend observed in the adipose of mice on the peroxidized n-3 diet also has been observed in people, and has been linked to underlying mechanisms of cardiovascular disease, cancer and neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), Parkinson’s disease, Alzheimer’s and Huntington’s disease.

“While we do not yet know if these findings in mice represent what happens in humans, and if the damage to adipose tissue truly has a whole-body negative consequence on health, it gives one pause in considering the source and quality of the n-3 fatty acids they eat,” says Townsend, who has discontinued taking a fish oil supplement out of an abundance of precaution based on data from the study. Instead, she focuses on fresh — instead of tinned — fish and plant sources of n-3 PUFAs, and a variety of dietary fats.

An article detailing the findings, “A peroxidized omega-3-enriched polyunsaturated diet leads to adipose and metabolic dysfunction,” was published online in February 2018 in ScienceDirect’s Journal of Nutritional Biochemistry.

Townsend fed 10-week-old male mice one of six custom diets for 16 weeks. The diets only differed in the amount and type of dietary fat, with high or low levels of saturated fats (SFA), omega-6 polyunsaturated fatty acids (n-6 PUFA) or n-3 PUFA. Protein and sucrose content was the same, as well as micronutrients. And caloric content was consistent among all the high- or low-fat groups.

As Townsend expected, based on studies exploring diets like the n-3 enriched Mediterranean diet that has gained popularity, mice on the high n-3 PUFA diet had a drastic reduction in weight gain and an improvement in parameters that indicate diabetes risk. This occurred despite their reduced expenditure of energy and no difference in food intake, a finding that was counterintuitive.

Townsend’s study also revealed an unexpected outcome: Despite apparent benefit to whole-body physiology, including decreased fat and body weight, mice on the enriched n-3 PUFA diet had fat tissue damage and dysfunction due to peroxidation.

The mice had fibrosis, or excess fibrous connective tissue that interferes with the tissue’s function; reduced anti-inflammatory response; presence of lipofuscin, a marker of tissue damage; and loss of proper nerve supply in white adipose tissue (WAT). WAT has a role in storing energy and releasing fatty acids when the body requires fuel, and plays other important roles in metabolism, and in the endocrine and immune systems.

Townsend found this same high level of peroxidation in common fish oil supplements measured by her lab and in food items high in n-3 PUFAs, including tinned sardines and salmon. Thus, Townsend says, any health benefits gained by taking the supplements may be outweighed by the risks.

In the U.S., there aren’t standards for peroxidation levels in fish oil supplements, and there is no market control of products. Other countries, says Townsend, do regulate these levels in supplements.

The study’s findings also are important for pets who eat fish-based foods that may be peroxidized.

Co-authors include James Miller, Magdalena Blaszkiewicz, Cordell Beaton, Cory Johnson, Stephen Waible II, Amanda Dubois and Amanda Klemmer from UMaine, and Michael Kiebish of the biopharmaceutical company BERG who analyzed lipid content in tissues after the six custom diets.

Johnson, a graduate student in the School of Biology and Ecology, will give a talk on the topic and ongoing work related to the study, “Sending Signals: Adipose Sensory Nerves May Communicate with the Brain via Lipid Metabolites,” on April 3 at a Keystone Symposium in Steamboat Springs, Colorado.

Contact: Beth Staples, 207.581.3777