A comprehensive study of phospholipid fatty acid rearrangements in metabolic syndrome: Correlations with organ dysfunction

Abstract

The balance within phospholipids (PLs) between saturated fatty acids and monounsaturated or polyunsaturated fatty acids is known to regulate the biophysical properties of cellular membranes. As a consequence, in many cell types, perturbing this balance alters crucial cellular processes, such as vesicular budding and the trafficking/ function of membrane-anchored proteins. The worldwide spread of the Western diet, which is highly enriched in saturated fats, has been clearly correlated with the emergence of a complex syndrome known as metabolic syndrome (MetS). MetS is defined as a cluster of risk factors for cardiovascular diseases, type 2 diabetes and hepatic steatosis; however, no clear correlations have been established between diet-induced fatty acid redistribution within cellular PLs and the severity/chronology of the symptoms associated with MetS or the function of the targeted organs. To address this issue, in this study we analyzed PL remodeling in rats exposed to a high-fat/high-fructose diet (HFHF) over a 15-week period. PL remodeling was analyzed in several organs, including known MetS targets. We show that fatty acids from the diet can redistribute within PLs in a very selective manner, with phosphatidylcholine being the preferred sink for this redistribution. Moreover, in the HFHF rat model, most organs are protected from this redistribution, at least during the early onset of MetS, at the expense of the liver and skeletal muscles. Interestingly, such a redistribution correlates with clear-cut alterations in the function of these organs.