The effects of long-term saturated fat enriched diets on the brain lipidome

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

Estimates of genomic heritability and genome-wide association study for fatty acids profile in Santa Inês sheep

Background: Despite the health concerns and nutritional importance of fatty acids, there is a relative paucity of studies in the literature that report genetic or genomic parameters, especially in the case of sheep populations. To investigate the genetic architecture of fatty acid composition of sheep, we conducted genome-wide association studies (GWAS) and estimated genomic heritabilities for fatty acid profile in Longissimus dorsi muscle of 216 male sheep. Results: Genomic heritability estimates for fatty acid content ranged from 0.25 to 0.46, indicating that substantial genetic variation exists for the evaluated traits. Therefore, it is possible to alter fatty acid profiles through selection. Twenty-seven genomic regions of 10 adjacent SNPs associated with fatty acids composition were identified on chromosomes 1, 2, 3, 5, 8, 12, 14, 15, 16, 17, and 18, each explaining ≥0.30% of the additive genetic variance. Twenty-three genes supporting the understanding of genetic mechanisms of fat composition in sheep were identified in these regions, such as DGAT2, TRHDE, TPH2, ME1, C6, C7, UBE3D, PARP14, and MRPS30. Conclusions: Estimates of genomic heritabilities and elucidating important genomic regions can contribute to a better understanding of the genetic control of fatty acid deposition and improve the selection strategies to enhance meat quality and health attributes

Brain Arachidonic Acid Incorporation and Turnover are not Altered in the Flinders Sensitive Line Rat Model of Human Depression

Brain serotonergic signaling is coupled to arachidonic acid (AA)-releasing calcium-dependent phospholipase A2. Increased brain serotonin concentrations and disturbed serotonergic neurotransmission have been reported in the Flinders Sensitive Line (FSL) rat model of depression, suggesting that brain AA metabolism may be elevated. To test this hypothesis, (14)C-AA was intravenously infused to steady-state levels into control and FSL rats derived from the same Sprague-Dawley background strain, and labeled and unlabeled brain phospholipid and plasma fatty acid concentrations were measured to determine the rate of brain AA incorporation and turnover. Brain AA incorporation and turnover did not differ significantly between controls and FSL rats. Compared to controls, plasma unesterified docosahexaenoic acid was increased, and brain phosphatidylinositol AA and total lipid linoleic acid and n-3 and n-6 docosapentaenoic acid were significantly decreased in FSL rats. Several plasma esterified fatty acids differed significantly from controls. In summary, brain AA metabolism did not change in FSL rats despite reported increased levels of serotonin concentrations, suggesting possible post-synaptic dampening of serotonergic neurotransmission involving AA

Topiramate does not alter expression in rat brain of enzymes of arachidonic acid metabolism

RATIONALE: When administered chronically to rats, drugs that are effective in bipolar disorder-lithium and the anticonvulsants, valproic acid and carbamazepine-have been shown to downregulate the expression of certain enzymes involved in brain arachidonic acid (AA) release and cyclooxygenase (COX)-mediated metabolism. Phase II clinical trials with the anticonvulsant topiramate [2,3:4,5-bis-O-(1-methylethylidene)-beta-D-fructopyranose sulfamate] suggest that this drug may also be effective for bipolar disorder. OBJECTIVES: To see if topiramate has effects similar to those of the other three drugs, we administered topiramate to rats for 14 days at 20 mg/kg, p.o. twice daily. RESULTS: Compared with p.o. vehicle, topiramate treatment did not significantly affect the brain activity or protein level of cytosolic phospholipase A2, secretory PLA2, or Ca2+-independent iPLA2. Additionally, brain protein levels of COX-1, COX-2, 5-lipoxygenase, and cytochrome P450 epoxygenase were unchanged. CONCLUSIONS: These results suggest that topiramate does not modify expression of the enzymes involved in brain AA metabolism that have been shown to be targeted by lithium, valproic acid, or carbamazepine. If topiramate proves effective in bipolar disorder, it may not act by modulating brain AA metabolism. In view of the proven anticonvulsant effect of topiramate, our results also suggest that the AA cascade is not involved in the anti-seizure properties of the drug

Topiramate does not alter the kinetics of arachidonic or docosahexaenoic acid in brain phospholipids of the unanesthetized rat

Interest in the potential therapeutic utility of topiramate for treating bipolar disorder was stimulated by published reports of investigator-initiated open label clinical studies. Because chronic lithium, carbamazepine and valproate decrease the turnover of arachidonic acid (AA) but not docosahexaenoic acid (DHA) in brain phospholipids of the awake rat, we tested if topiramate would produce similar results. Rats received either topiramate (20 mg/kg twice per day) or vehicle for 14 days and then while unanesthetized were infused intravenously with either [1-(14)C] AA or [1-(14)C] DHA for 5 min while blood was collected from the femoral artery at fixed times. Topiramate did not alter the incorporation rate of AA or DHA from their respective brain acyl-CoA pool into brain phospholipids, nor the turnover of AA and DHA in brain phospholipids. The results of our study indicate that topiramate does not possess a pharmacological property that three drugs with proven efficacy in treating bipolar disorder have in common