two for flinching.
Beyond Fish Oil: the hunt for small molecules with a big omega-3 punch
The modern Western diet is abundant in fat, especially omega-6 fatty acids. And while there’s nothing inherently unhealthy about these fats, when the ratio of omega-6 to omega-3 fatty acids in our diet is high our body chemistry shifts to a pro-inflammatory state.
This means that if we have arthritis we may ache a bit more, and if we have type 2 diabetes our cells may become less adept at detecting and responding to insulin. Our bodies may be more prone to obesity, as well.
Although consumption of omega-3 fatty acids found in high concentrations in cold-water marine species such as salmon and krill can help reduce chronic inflammation and insulin resistance, researchers at the University of California, San Diego School of Medicine say that the amount of fish or even fish oil needed to reverse insulin resistance is too high to be practical.
In light of this roadblock, they have taken another tack in their efforts to develop novel anti-diabetic treatments. Specifically, they are working to chemically construct a better fish oil – one that is more effective and specific for human medicine, and which has the added benefit of not depleting marine species.
In previous work, they elucidated the molecular mechanism that makes omega-3 fatty acids effective in reducing chronic inflammation and insulin resistance. In a new paper, published in Nature, they report synthesizing a molecule, dubbed Compound A, in mice that activates the same beneficial pathway as omega-3 fatty acids. Interestingly, Compound A is not present in fish oil but it nonetheless binds to a key protein receptor activated by omega-3 fatty acids.
“What we have done is built a small molecule that sets in motion the same molecular cascade as omega-3 fatty acids,” said lead author Da Young Oh, PhD, an assistant professor in the Division of Endocrinology and Metabolism. “The difference is that the small molecule is more selective and suitable for developing pharmaceutical grade product than fish oil.”
Researchers are now collaborating with a major pharmaceutical company to develop a small-molecule, insulin-sensitizing agent for the treatment of type 2 diabetes and other human insulin-resistant states.