Targeting inflammation and mitochondria with dietary linoleic acid for cardiometabolic health when research comes full circle

As a new graduate student, I was eager to study the new theory that fish oil rich in long chain omega 3 fatty acids would be protective against skin cancer due to their anti-inflammatory properties.  Lo and behold, the fish oil diet had some effects on prostaglandin species but no effect on cancer.  Surprisingly, diet rich in linoleic acid (LA) protected against skin cancer in a dose responsive manner.  From this point forward, I was infected with the bug that biology is complex and not always what you calculate on paper. Over the 30 years of my career, my lab has evolved to now study how LA impacts mitochondrial respiration.  We conduct our studies based on the solid knowledge that low levels of LA-rich cardiolipin, e.g., 4-LA cardiolipin, reduce mitochondrial respiration and therefore, ATP synthesis.  Because LA is a required nutrient that cannot be endogenously synthesized, the diet is the only way to increase LA, and therefore support 4-LA-cardiolipin turnover in mitochondria.  In a mouse model of middle age, we have discovered that a diet enriched with LA oil increases hind limb strength and lean mass.  Further, we show that LA diet increased 4-LA-cardiolipin and mitochondrial respiration in skeletal muscle, liver and brown adipose tissue.  The effects occur without changes of markers of inflammation.  We have now shown that fortifying the diets of healthy adults with a modest amount of LA-rich oil also increases 4-LA-cardiolipin and mitochondrial respiration. The implications of our findings for cardiometabolic health will be discussed.