Evert de Vries

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. Methods: 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. Results: 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. Conclusions: These analyses provide potential biomarkers for the diagnosis of diet-induced lipid accumulation in heart and hind-limb muscle tissue.

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.

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.

Comparison of Hormones, Lipoproteins and Substrates in Blood Plasma in a C57bl6 Mouse Strain after Starvation and a High Fat Diet: A Metabolomics Approach

Male C57bl6 mice (age 8-12 weeks) were fed a high-fat diet, containing 0.25% cholesterol (Ch) and 24% energy from bovine lard for a period of approximately 40 days or were exposed to 24 hours of starvation. Exposure to 24 hours of starvation, resulted in a significant drop in plasma glucose (1.8-fold), Phospholipids (PL) (1.2-fold), Triacylglycerols (TG) (1.4-fold), Total Cholesterol (TCh) (1.4-fold), Free cholesterol (FCh) (1.4-fold) and a significant increase in Ketone bodies (9.6-fold). After 24 hours of starvation plasma Very Low Density Lipoproteins- (VLDL), Low Density Lipoproteins-(LDL) and High Density Lipoproteins-(HDL) TCh and-Phospholipids (PL) were unaffected, while VLDL TG was significantly decreased and LDL and HDL TG significantly increased. Plasma Free Fatty Acids (FFA) and Insulin were unaffected. In the high-fat diet group plasma VLDL-, LDL- and HDL-TCh and -PL were significantly increased as compared to the values on regular chow diet before starting the diet-feeding period. Furthermore, a significant rise in VLDL-TG was found. The high fat diet resulted in significantly elevated levels of plasma TCh (2.9-fold), FCh (3.4-fold), PL (2.5-fold) and Insulin (4.4-fold) compared to the Control group that was fed regular chow diet, while glucose and Free Fatty Acids (FFA) levels were unaffected. The increase in Insulin as a result of a fatty diet may be indicative for increased insulin insensitivity.