MGH shows fatty acid ratio affects risk for chronic disease

The ratio of omega-6 and omega-3 fatty acids, rather than the total amount of them, influences risk of developing chronic disease, according to new research from Massachusetts General Hospital (MGH) in Boston, which was published in the journal Nature’s Communications Biology.

The team, led by Jing Kang, MD, PhD, senior author, director of the Laboratory for Lipid Medicine and Technology at MGH, and associate professor of Medicine at Harvard Medical School, created several novel mouse models for studying health effects of omega-6 and omega-3 fatty acids. The role of polyunsaturated fatty acids (PUFAs) in human health has long been debated but is of great interest. They are one of many factors thought to influence chronic disease, such as obesity, type 2 diabetes, cardiovascular disease, and cancer, but studies have shown inconsistent results regarding exactly how they impact risk.

The MGH research used new mouse models that helps eliminate some of the myriad confounding dietary factors that affect studies in this field. The transgenic mice used are identical, except in the levels of n-6 and n-3 they naturally produce, whatever their diet.

The researchers used four strains of mice for their study, a wild type or "normal" mouse, and three related mouse strains engineered to produce varying levels of n-6 and n-3 PUFA, no matter what they were fed. These mice can synthesize sufficient levels of specific PUFAs to adjust for dietary factors that would normally disrupt PUFA levels, according to the study abstract.

The MGH team studied whether the four types of mice showed different rates of metabolic disorders, including metabolic endotoxemia, systemic inflammation, obesity, fatty liver, glucose intolerance, and cancer. The mice that over-produced n-6 PUFA had a higher risk of metabolic disease and cancer, while mice able to convert n-6 to n-3, thereby lowering the ratio, showed a healthier phenotype. The researchers were also able to uncover details about the molecular interactions between these fatty acids and biological networks. For example, the alteration of the PUFA n-6 to n-3 ratio led to changes in the gut microbiome and fecal and serum metabolites.

Kang and his team are currently working on translational research to explore the clinical utility of a balancing intervention and the feasibility of using the tissue omega-6/omega-3 ratio as a new health biomarker.

"Many lines of evidence now support the notion that the omega-6/omega-3 imbalance is a critical factor that contributes to the development of chronic disease," Kang said. "Balancing the PUFA ratio may be a safe and effective solution to some modern health problems."