Fatty acids may cause insulin resistance by altering oxidation and leading to citrate buildup, inhibiting phosphofructokinase and increasing glucose-6-phosphate.

“prior to this people workers biochemists you may know the name philip randall he did some pioneering studies in the 60s at university of bristol and was really the first to say hey fatty acids may be toxic may be causing insulin resistance and did studies in rat tissue you know cells heart tissue diaphragm muscles taken from rats in vitro incubated it with fatty acids and in vitro in the test tube induced insulin resistance the mechanism that they postulated was that it was altering basically oxidation the tca cycle citrate levels would build up and lead to inhibition of phosphofructokinase which is a key glycolytic enzyme the prediction that randall made was glucose 6-phosphate should increase leading to inhibition of hexokinase”