Nutraceutical Interventions and Lipoprotein Characterisation: Strategies for Cardiovascular Risk Management
[eng] Introduction: Cardiovascular diseases (CVDs) represent the leading cause of death globally (32%), with atherosclerosis as the main underlying pathology. Dyslipidemia is one of the most influential risk factors in the development of atherosclerotic cardiovascular disease (ACVD), with low-densit...
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| Format: | doctoral thesis |
| Status: | Published version |
| Publication Date: | 2025 |
| Country: | España |
| Institution: | Universidad de Barcelona |
| Repository: | Dipòsit Digital de la UB |
| OAI Identifier: | oai:dnet:ubarcelona__::675ef6b024ec7aca28678f1a0793c65a |
| Online Access: | https://hdl.handle.net/2445/228747 https://hdl.handle.net/10803/697202 |
| Access Level: | Open access |
| Keyword: | Malalties cardiovasculars Aterosclerosi Lipoproteïnes de baixa densitat Colesterol Cardiovascular diseases Atherosclerosis Low density lipoproteins Cholesterol |
| Summary: | [eng] Introduction: Cardiovascular diseases (CVDs) represent the leading cause of death globally (32%), with atherosclerosis as the main underlying pathology. Dyslipidemia is one of the most influential risk factors in the development of atherosclerotic cardiovascular disease (ACVD), with low-density lipoprotein cholesterol (LDLc) being the main target of lipid-lowering therapies. However, small and dense low-density lipoprotein particles (LDLp) increase cardiovascular risk even when LDLc levels are optimal. Although high-density lipoprotein cholesterol (HDLc) is considered protective, the quality and functionality of high-density lipoprotein (HDL) count as much as its quantity. This highlights that the composition, size, number, and functionality of lipoproteins are crucial in determining their atherogenicity or atheroprotection. In addition, factors such as sex, obesity, and lipid background are associated with differences in the pattern of lipoprotein subclasses, contributing to a more or less favorable cardiovascular status. Growing evidence associates hypercholesterolemia with dysbiosis of the gut microbiota. The gut microbiota acts as an endocrine organ and influences various metabolic processes, including lipid metabolism. Therefore, the administration of nutraceutical supplements that act at the intestinal level has been considered a useful tool to improve the metabolic profile and help in the control of conditions such as dyslipidemia, obesity, or diabetes. Objectives: In this doctoral thesis we aimed to: a) investigate the effects of regular and continuous intake of a probiotic based in Lactiplantibacillus plantarum on lipid metabolism, including lipoprotein profiles, pattern of bile acids (BAs), metabolic and inflammatory markers in overweight and obese individuals without a known history of CVDs; b) investigate the effects of regular and continuous intake of a polysaccharide containing β-glucan/chitin-chitosan (βGluCnCs) in overweight and obese individuals without a known history of CVDs; and, c) perform advanced lipoprotein characterization in samples of various human cohorts. Methods: Lipid profile and hepatic and renal variables were assessed by standardized biochemistry. Lipoprotein profile (composition, number, and size), glycoproteins, lipids, and low molecular weight metabolites were performed by proton nuclear magnetic resonance (1H-NMR). Lipoprotein functionality was evaluated by conjugated dienes, total radical trapping antioxidant potential [TRAP] (antioxidant potential of HDL), and HDL cholesterol efflux assays. BAs pattern was assessed by ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS). Markers of inflammation and glucose metabolism, adipokines, fibroblast growth factor (FGF)-19, and apolipoprotein (Apo)B48 and ApoB100 were measured by immunoassays [Enzyme linked immunosorbent assays (ELISAs) and Multilplex]. Serum levels of lipoprotein(a) [Lp(a)], ApoA-I and ApoB were determined by immunoturbidimetric assays. Results: Probiotic intake reduced conjugated BAs, FGF-19, ApoB100 and ApoB48 levels, small LDLp concentration, and low-density lipoprotein (LDL) susceptibility to oxidation, while enhancing HDL antioxidative activity. βGluCnCs supplementation increased HDLc levels and HDLc/total cholesterol (TC), HDLc/Non-HDLc ratios, and ApoA-1/ApoB, particularly in women, and in individuals with overweight and LDLc levels below 130 mg/dL. Moreover, βGluCnCs reduced the concentration of ApoB, particularly in men. Additionaly, βGluCnCs reduced non-HDLc and LDLc, and improved HDL antioxidant capacity in individuals with LDLc levels equal or above 130 mg/dL. Advanced lipoprotein characterization identified differential features and attributes in women and men and in overweight and obese individuals. Conclusions: In an apparently healthy overweight/obese population with no additional cardiovascular risk factors, our results showed that consumption of Lactiplantibacillus plantarum KABP011, KABP012, and KABP013 induced changes in the BAs and lipoprotein profile, reduced LDL susceptibility to oxidation, and increased HDL antioxidant capacity, suggesting a pattern of protection against atherosclerosis. Consumption of βGluCnCs leads to increased HDLc and reduced ApoB levels, with the response depending on sex and baseline LDLc levels. Finally, men and obese individuals have a higher-risk lipoprotein subclass profile compared to women and overweight individuals. |
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