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Browsing by Subject "CVD"

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  • Mass Spectrometry-Based Lipidomics Indicates that Consumption of Fatty Fish Alters the lipid species Profile of Human LDL 
    Bhalke, Monika (2020)
    Lipoproteins are biochemical carriers of the insoluble lipids. They are complexes combining lipids and proteins for the transport of lipids. Amongst the type of lipoproteins are low-density lipoproteins (LDL) which are prevalent in various diseases such as obesity, diabetes, atherosclerosis, and other cardiovascular diseases (CVD). Omega-3 fatty acids are polyunsaturated fatty acids (PUFA) that are essential components of lipid metabolism and play a significant role in the human diet. Omega-3 PUFAs such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are derived from fish and are necessary for proper cardiovascular functioning. Because the human body is unable to produce enough quantities of some omega-3, diet is an important source for its availability. When a diet is rich in saturated fats, the above-mentioned diseases transpire. This study investigated how consumption of two fish diets, Lean fish and Fatty fish, influence the lipid species of human LDL particles. The lipid species analysed in this study are phospholipids such as phosphatidylcholine (PC), sphingomyelin (SM), and lysophosphatidylcholine (LPC), and cholesteryl esters (CE), and triacylglycerols (TAG). A total of 42 volunteers with a history of impaired fasting glucose had randomly been divided into two groups: fatty fish (4 fish meals/week) and lean fish (4 fish meals/week) for 12 weeks. Blood samples had been collected from the volunteers before and after consumption of the fish meals and LDL particles had been isolated from the blood samples by ultracentrifugation. In this study, the lipids were extracted by Folch method, and the extracted lipids were analysed using Triple quadrupole mass spectrometry. The lipid class profile did not change due to the two fish type diets. However, the consumption of fatty fish diet increased the levels of lipid species of PC, LPC, and CE containing EPA and DHA acyl chains, while decreasing levels of several TAG species. Lean fish induced minor changes in the lipid composition of LDL particles. Based on these results, fatty fish diet alters the plasma LDL lipidome profile with changes induced to both the surface and the core composition of the LDL particles in a positive way regarding cardiovascular health.
  • Rare lipid altering genetic variants and their effects on diabetic complications 
    Hotakainen, Ronja (2019)
    Diabetes is a group of chronic metabolic disorders caused by the inability of the body to produce or utilize insulin efficiently. Globally, diabetes affects over 422 million people (WHO 2014) and one third of the patients suffer from diabetes-related complications, which cause a considerable economic burden on the healthcare. Diabetic kidney disease (DKD) is one of the most severe complications, since one in five patients develop end-stage renal disease, which requires dialysis or kidney transplantation for survival. In addition, diabetes is a risk factor for cardiovascular disease (CVD), the most common cause of mortality among individuals with diabetes. Conventional clinical risk factors for both DKD and CVD have been established and include an altered lipoprotein profile, an abnormal glucose balance and hypertension. While the clinical risk factors are fairly well recognized, the genetic background of both DKD and CVD is rather unknown. The aim of this thesis was to study the effects of rare genetic variants altering lipids and other cardiometabolic risk factors and to determine their impact on diabetic complications. This study focused on loss of function and missense variants from whole exome- (N=500) and whole genome sequencing data (N=600) in type 1 diabetics from the Finnish Diabetic Nephropathy Study cohort. Single variant and gene-based association analysis were used to detect lipid-associated genetic variants and suggestive genes involved in lipid metabolism. Meta-analysis of whole exome- and whole genome single variants was performed to increase the sample size and detect additional lipid-associated variants. Three lipid-associated variants were genotyped in a cohort of 3000 patients to confirm the detected associations. Single variant association analysis detected a novel, previously unpublished, 21bp deletion located in the RBM47 gene, which was associated with lower apoC-III serum concentrations. To fully understand the impact of the 21bp deletion in RBM47 on apoC-III, further studies investigating the role of RBM47 in lipid metabolism are requested. Furthermore, single variant meta-analysis detected several lipid-associated variants. We showed that the rs451195 in PPIC was significantly associated with DKD. This study sheds light on the genetic background of diabetic dyslipidemia.

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