The Effects of Long-Term Saturated Fat Enriched Diets on the Brain Lipidome

Abstract

The brain is highly enriched in lipids, where they influence neurotransmission, synaptic plasticity and inflammation. Non-pathological modulation of the brain lipidome has not been previously reported and few studies have investigated the interplay between plasma lipid homeostasis relative to cerebral lipids. This study explored whether changes in plasma lipids induced by chronic consumption of a well-tolerated diet enriched in saturated fatty acids (SFA) was associated with parallel changes in cerebral lipid homeostasis. Male C57Bl/6 mice were fed regular chow or the SFA diet for six months. Plasma, hippocampus (HPF) and cerebral cortex (CTX) lipids were analysed by LC-ESI-MS/MS. A total of 348 lipid species were determined, comprising 25 lipid classes. The general abundance of HPF and CTX lipids was comparable in SFA fed mice versus controls, despite substantial differences in plasma lipid-class abundance. However, significant differences in 50 specific lipid species were identified as a consequence of SFA treatment, restricted to phosphatidylcholine (PC), phosphatidylethanolamine (PE), alkyl-PC, alkenyl-PC, alkyl-PE, alkenyl-PE, cholesterol ester (CE), diacylglycerol (DG), phosphatidylinositol (PI) and phosphatidylserine (PS) classes. Partial least squares regression of the HPF/CTX lipidome versus plasma lipidome revealed the plasma lipidome could account for a substantial proportion of variation. The findings demonstrate that cerebral abundance of specific lipid species is strongly associated with plasma lipid homeostasis.

Chain length of saturated fatty acids regulates mitochondrial trafficking and function in sensory neurons

“…The Western diet is enriched in SFAs that are linked to the development of neurodegenerative diseases (52)(53)(54).…”

The involvement of astrocytes in early‐life adversity induced programming of the brain

“…The uptake of peripheral lipids by the brain has been subject of debate (Schönfeld & Reiser, 2013). Certain circulating peripheral lipids (e.g., PUFAs) might freely enter the brain (Giles et al, 2016;Nguyen et al, 2014), while others (e.g., cholesterol and phospholipids) are prevented from entering by the BBB and need to be synthesized within the brain (Edmond, 2001;Jurevics & Morell, 1995). In contrast to neurons which are inefficient in lipid synthesis, astrocytes are highly active in de novo lipid synthesis (Camargo et al, 2012;Hofmann et al, 2017;Nieweg, Schaller, & Pfrieger, 2009;Pfrieger & Ungerer, 2011;van Deijk et al, 2017) and subsequent transport of lipids to neurons (Boyles, Pitas, Wilson, Mahley, & Taylor, 1985;Mauch et al, 2001;Nieweg et al, 2009;Pfrieger & Ungerer, 2011).…”

The PI 3‐kinase PI3KC2α regulates mouse platelet membrane structure and function independently of membrane lipid composition

“…Platelet lipid composition analyses were performed as previously described [13,14]. Briefly, lipids were extracted using a single-phase chloroform : methanol extraction.…”

“…Lipid analysis was performed using liquid chromatography electrospray ionizationtandem mass spectrometry, as previously described in detail [13,14], using an Agilent 1200 UHPLC coupled to an AB Sciex Q/TRAP 4000 mass spectrometer (SCIEX, Framingham, MA, USA) with a turboionspray source (350°C) and Analyst 1.5 and Multiquant data systems (SCIEX). Separation by liquid chromatography was performed on a Zorbax C18 column (1.8 lm, 50 9 2.1 mm; Agilent Technologies, Santa Clara, CA, USA), again as previously described [13,14]. In total, 294 lipids were detected and quantitated.…”