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

Abstract

The balance within phospholipids (PL) between Saturated Fatty Acids (SFA) and mono-or poly-Unsaturated Fatty Acids (UFA), is known to regulate the biophysical properties of cellular membranes. As a consequence, perturbating this balance alters crucial cellular processes in many cell types, such as vesicular budding and the trafficking/function of membrane-anchored proteins. The worldwide spreading of the Western-diet, which is specifically enriched in saturated fats, has been clearly correlated with the emergence of a complex syndrome, known as the Metabolic Syndrome (MetS), which is defined as a cluster of risk factors for cardiovascular diseases, type 2 diabetes and hepatic steatosis. However, no clear correlations between diet-induced fatty acid redistribution within cellular PL, the severity/chronology of the symptoms associated to MetS and the function of the targeted organs have been established. In an attempt to fill this gap, we analyzed in the present study PL remodeling in rats exposed during 15 weeks to a High Fat/High Fructose diet (HFHF) in several organs, including known MetS targets. We show that fatty acids from the diet can distribute within PL in a very selective way, with PhosphatidylCholine being the preferred sink for this distribution. Moreover, in the HFHF rat model, most organs are protected from this redistribution, at least during the early onset of MetS, at the exception of the liver and skeletal muscles. Interestingly, such a redistribution correlates with clear-cut alterations in the function of these organs.

Polyunsaturated phospholipids increase cell resilience to mechanical constraints

“…The brain is the organ which displays the most discrepancies between PLs, PC being predominantly DB=1, whereas PE and PS are essentially DHAenriched. These observations nicely match previous observations made in rats (5).…”

“…Saturated and Monounsaturated FA originating from a high-fat diet preferentially accumulate in rats within PC in their liver and skeletal muscles, in a process that occurs at the expense of PUFA. Interestingly, this FA redistribution is paralleled by a global decrease in muscle strength (5).…”

“…Interestingly, organs display very characteristic fatty acid profiles within their phospholipids (5). This results from the activity of acyl transferases, which selectively incorporate defined fatty acids into PLs (6,7).…”

“…When considering PC, rat organs display very characteristic fatty acid distributions within PLs and, therefore various saturation rates: they can be classified as DB=0/saturated organs (Spleen, lung), DB=1 (Brain), DB=2 (Pancreas) and DB>2 organs (liver, muscle and cardiovascular system) (5).…”

“…The main PUFA species found within PLs are the ω-6 Arachidonic Acid (AA) and the ω-3 Docohexaenoic Acid (DHA). In rats, one can differentiate AA-(liver and Cardiovascular system) and DHA-enriched (skeletal muscle) organs (5).…”