Vincent van Ginneken

On the Futile Existence of DHA, None of EPA and the Predominant Roleof the Triacylglycerols (TGs) in the Post Mortem Human Brain: An LCMSStudy with Evolutionary Implications

What is known about the brain is a scanty amount of information despite its importance in human evolution. Here we perform based on a holistic Systems Biology lipidomics approach an attempt describing the brain biochemical lipid composition based on the homogenate of a part (gyrus) of the neocortex of post mortem material of the “Dutch Brain Bank” with LCMS techniques. From evolutionary perception the occurrence of the “fish oils” in blood and/ or brain is interesting and their ability to pass the Blood-Brain Barrier (BBB). Both omega-3 “fish oil” Fatty Acids (FA) Eicosapentaenoic Acid (EPA) and Docosahexaenoic Acid (DHA). EPA and DHA are found in rather high concentrations respectively 0.277% and 0.258% respectively in blood plasma but not in the brain. EPA is not found in grey or white neocortex matter so probably it cannot pass the BBB while this is the case for DHA giving values of respectively ≈0.00015% while Triacylglycerols (TGs) are the major constituent of the human brain with a mean value of the neocortex of ≈72%. We finally conclude the TGs have played a major role in the process of human brain growth and encephalization during course of evolution.

Metabolomics in Hind limb and Heart Muscle of a Mouse Model after aHigh-fat Diet

Objective: Dysregulation of FA metabolism in heart muscle is a major problem associated with the metabolic syndrome. nMethods: C57Bl/6 mice were fed for 40 days a high-fat diet (+0.25% cholesterol 45% energy from bovine lard). High Performance Thin Layer Chromatography (HPTLC) was used to measure Triacylglycerol’s (TG) and Free Cholesterol (FCh) in hearts and hind limb muscle of mice. With LC-MS techniques we measured Cholesterol esters (ChE), lysophosphatidyl-cholines (LPC), phosphatidylcholine (PC), sphingomyelin (SPM) and Triacylglycerol’s (TG) in hind limb and heart muscle after 40 days of a fatty diet. nResults: This study was designed to give more insight in the lipid composition of the heart muscle in comparison to hind limb muscle. Only in the heart muscle cholesterol esters (ChE) were observed. This was confirmed with LC-MS techniques. Especially the 20:3-ChE are significantly increased in the fatty heart with 1317%. The LC-MS techniques gave no clear picture for Lysophosphatidyl-cholines (LPC), Sphingomyelin (SPM) in hind limb and heart muscle after 40 days of a fatty diet. Only for Phosphatidylcholine (PC) the most remarkable observation was that 36:1-PC rises in heart muscle with 4000%. Twenty-three triglycerides were measured in hind limb muscle but no effect was observed after 40 days of high-fat diet. In contrast, in the heart muscle four types of TG increased dramatically after a 40 days fatty diet ( 54:2-TG (+394%), 54:3-TG (+452%), 56:3-TG (+297%) and 56:5-TG (+213%). Based on Principal Component Analysis with different lipid compounds like LPC, SPM, TG, PC and ChE, a separation can be made for high-fat diet fed animals and control diet fed animals both for hind limb muscle and heart muscle. After elimination of the TG and the ChE and a new PCA run we see that four groups can be clearly separated: Control-heart, Fat-heart, Control-hind limb muscle and Fat-hind limb muscle. nConclusions: These analyses provide potential biomarkers for the diagnosis of diet-induced lipid accumulation in heart and hind-limb muscle tissue.

Seaweed Competition: Ulva Sp. has the Potential to Produce the Betaine Lipid Diacylglyceryl-O-4’-(N,N,N,-Trimethyl) Homoserine (DGTS) in Order to Replace Phosphatidylcholine (PC) Under Phosphate-Limiting Conditions in the P-Limited Dutch Wadden Sea and Outcompete an Aggressive Non-Indigenous Gracilaria vermiculophylla Red Drift Algae Out of this Unique Unesco World Heritage Coastal Area

The present study tested in the Western Dutch Wadden Sea (WDW) UNESCO World Heritage Site why an on a global scale the aggressive non-indigenous red drift alga Gracilaria vermiculophylla didn’t succeed to overgrow the WDC. In such a multifaceted complex ecosystem like the dynamic WDC it seems like unraveling a Gordian knob in order to describe the inextricable relationship between this seaweed invader suppression and its (a) biotic environment. However, we succeeded at the molecular level to give a convincing reasoning at first grounded in the awareness of a since 1987 river Rhine-North-Sea-WDC severely Phosphorus (P) restricted ecosystem. Our ecological datasets gave via final DCA (Detrended Correspondence Analysis) awareness of the very compelling interaction between Ulva sp. and G.vermiculophylla. Based on LCMS-techniques we discovered that Ulva sp. have the advantage to use the biochemical pathway solely rarely observed in some euckaryotes- to have the potential to produce the betaine lipid diacylglyceryl-O-4’-(N,N,N,-trimethyl)homoserine (DGTS) which replaces the plant/seaweed cell wall structure phosphatidylcholine (PC) “lecithine” under phosphate-limiting growth conditions. Also we hope this lipidomics based compound DGTS can serve as an ecological biomarker in order to protect vulnerable ecosystems like the Wadden Sea (UNESCO World Heritage).

Type 3 Diabetes Reflects Disordered Lipid Metabolism in the HumanBrain Related to Higher Degree of Unsaturated Fatty Acids Compositionand is not Related to Body Mass Index

In this study we investigated lipid profiles of brain of post mortem type 2 diabetes patients T2DM elderly patients in comparison to a Control group (Co) of the “Netherlands Brain Bank” using LCMS techniques. Here we report that brains of these T2DM patients contain more double bonds and consequently are more rigid. In a small cohort (≈200 patients) we prove that these brain diseases are not interrelated with BMI so obesity is not a major cause. The predicted wave of brain diseases of mild-Alzheimer (m-AD), dementia and depression of the “baby boom generation” might be evolved due to the “fatty” and more “rigid” brain structure due to the quality of fats eaten during earlier lifespan. Our major conclusion is that diabetes and its treatment among T2DM patients are more associated with structural disturbances (lipid composition) in the brain than with glycaemic control. Therefore we introduce the new terminology “Type 3 diabetes” (T3DM) referring to the mental disorders as a consequence of a disordered lipid metabolism in the human brain related to higher degree of unsaturated fatty acids composition.

Characterization of the lipid profile post mortem for Type-2 diabetes in human brain and plasma of the elderly with LCMS-techniques: a descriptive approach of diabetic encephalopathy

Objectives: This study was designed to give more insight in the lipid profile of brain and blood plasma for post mortem type 2 diabetic (T2DM) elderly patients in comparison to a Control group (Co) to give a descriptive approach of diabetic encephalopathy. Methods: Reversed phase liquid chromatography coupled to mass spectrometry (LC-MS) was used to quantify and qualify the rearrangement and repartitioning of fat stores in the brain of male post mortem subjects (Co n=8; 73.5 ± 10.5 years; T2DM, n=8; 77.3 ± 7.2 years) which were obtained from the ‘Netherlands Brain Bank’. Differences were calculated by a Principal Component Analysis (PCA). Results: We observed that the saturation index of the Cholesterylester for 16:0 was significantly higher in white matter of T2DM patients in comparison to white matter of the control group (P≤0.05) which was earlier observed in schizophrenic postmortem brain subjects [1]. Furthermore we can conclude there are no significant difference between summarized relative concentrations of the different lipid compounds in human brain homogenate (white vs. grey) of two patients groups: one Control-group (N=8) and one Diabetes-2 (T2DM) group (N=8). For three Monoglycerides the values were significantly higher in the T2DM group. For 18:2 MG (P≤0.048, increase with 193.4%); for 20:3 MG (P≤0.048, increase with 270.0%) and for 24:3 MG (P≤0.036, increase with 222.5%). No other significant differences in brain lipid composition were observed between the control and T2DM group. In T2DM patients plasma lipid profiles (109 components) were more scattered. Few differences in plasma fat composition (triacylglycerols, free fatty acids (NEFA), cholesterol, (HDL)-cholesterol) were observed between the Co and T2DM group. Plasma fructosamine was significantly higher in T2DM patients which was a reliable indicator for type 2 diabetes. Conclusion: Diabetic encephalopathy which often occurs in T2DM patients can probably more described to microvasculair complications and/or changes in the saturation degree of the several lipid compounds especially for C16:0. Saturation degree issues will be worked out in another manuscript. Our major conclusion is that diabetic encephalopathy in T2DM patients is not the result of an aberrant lipid metabolism.

Hunter-prey correlation between migration routes of African buffaloes and early hominids: Evidence for the “Out of Africa” hypothesis

Based on the similarity of migration routes of early bovines and early hominids (direct hunter-prey correlation) we postulate the hypothesis that early hunter hominids followed the herds of buffaloes and that the dispersal of early hominids pan-Africa is directly correlated to the historical migration of the African buffalo. This reasoning gives supportive evidence for the “Out of Africa” hypothesis. In addition, brain fattening (“brain steatosis”) has previously been demonstrated after exposure of a juvenile mouse strain to a bovine lard High-Fat diet and starvation -as an evolutionary paradoxin whole brain using LCMS-techniques [1]. Here we postulate the hypotheses that accumulation of specific Triacylglycerols from bovine lard (large amounts of unsaturated C:50-1; C:50-2; C:52-2; C:52-3; C:54-3;C:54-4 and C:56-3 TGs) in early hominid brain could have contributed to encephalization in human evolution. Following this lipidomics based scientific approach [2] we gave supportive evidence for the “Out of Africa” hypothesis.