Led by senior author, Dr. Michael Karin, distinguished professor of pharmacology at UCSD's Laboratory of Gene Regulation and Signal Transduction, researchers set out to understand why saturated and unsaturated fats produce opposite effects in the body, theorizing that something in cell membranes must be able to differentiate between saturated and unsaturated fats.

Saturated fatty acids, such as palmitic acid, are potent activators of enzymes called Jun kinases (JNK), molecules that are implicated in the development of type 2 diabetes, insulin resistance, obesity, and atherosclerosis. Unsaturated fatty acids like palmitoleic acid (POA) and eicosapentaenoic acid (EPA) work in an opposite manner. They block the activation of JNK by palmitic acid.

The key difference between palmitic acid and palmitoleic acid is one unsaturated bond, meaning that two hydrogen atoms are missing in the latter. Saturated fatty acids have rigid hydrocarbon tails while unsaturated fatty acids have bent hydrocarbon tails. The incorporation of saturated fatty acids into the cell decreases cellular membrane fluidity.

It appears that the cell membrane is the only structure in the cell that can differentiate between saturated and unsaturated fatty acids so the researchers looked for membrane-associated protein kinases that could explain the different effects on JNK activity. An enzyme identified as c-Src, which resides within the cell membrane, seems to be responsible for the activation of JNK by palmitic acid and other saturated fatty acids.

Saturated fats smother and push c-Scr into the cell membranes, literally clogging membranes at the molecular level and disrupting basic metabolism. Jun kinases set into motion the chemical reactions that cause insulin resistance and cardiovascular disease. Unsaturated fats, such as POA and EPA, work in an opposite manner and block the accumulation of c-Src, thus preventing the chain of events that lead to health problems.

"These findings not only explain the long-standing enigma regarding the different health effects of saturated and unsaturated fatty acids, they also provide improved tools and a mechanistic framework for the potential development of dietary supplements to treat obesity, estimated to be worth billions of dollars per year," said Karin in a press release.

The study was published in the journal Cell.

Image: oksana2010/Shutterstock.

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