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Related Concept Videos

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Coronary Artery Disease I: Introduction01:30

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Lipid Catabolism01:25

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Triglycerides serve as crucial long-term energy storage molecules in microorganisms, providing a dense source of metabolic energy. Their breakdown is mediated by lipases, which hydrolyze triglycerides into glycerol and free fatty acids. Each of these components follows distinct metabolic pathways, ultimately contributing to ATP synthesis and cellular energy homeostasis.Glycerol MetabolismGlycerol, released from triglyceride hydrolysis, is phosphorylated by glycerol kinase to form...
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Atherosclerosis III: Management01:26

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Lipid-derived Compounds in the Human Body01:31

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Updated: Jan 18, 2026

Differential Effects of Lipid-lowering Drugs in Modulating Morphology of Cholesterol Particles
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Ratio-Driven Lipoprotein Mapping Refines Genetic Pathways of Cardiometabolic Risk.

S Hani Najafi-Shoushtari1,2, Karsten Suhre3,4, Murugan Subramanian5

  • 1Bioinformatics Core, Weill Cornell Medicine-Qatar, Education City, 24144 Doha, Qatar.

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|January 16, 2026
PubMed
Summary
This summary is machine-generated.

This study fine-mapped genetic risk loci for dysregulated blood lipids using UK Biobank data. Novel ratio-based markers were identified, revealing new insights into lipoprotein metabolism and potential drug targets for cardiovascular disease.

Keywords:
cardiovascular diseasedrug target developmentgenetic associationlipid and cholesterol metabolismlipo-proteomicslipoprotein particle compositionmicroRNA

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Area of Science:

  • Genetics
  • Metabolomics
  • Cardiovascular Disease Research

Background:

  • Dysregulated blood lipids are key predictors of cardiovascular events.
  • Genome-wide association studies (GWAS) have identified numerous genomic regions linked to lipid metabolism.
  • Translating genetic associations into clinical applications requires understanding gene functions in lipoprotein metabolism, transport, and remodeling (LPmtr).

Purpose of the Study:

  • To perform deep molecular fine-mapping of lipid risk loci using lipoprotein-related traits and their ratios.
  • To identify novel ratio-based markers for LPmtr pathways.
  • To generate new hypotheses for drug target development and uncover mechanisms in hyperlipidemia.

Main Methods:

  • Deep molecular fine-mapping of 554 lipid risk loci using 168 lipoprotein-related traits and their ratios in 273,000 UK Biobank participants.
  • Analysis of ratio-based markers, including linoleic acid fraction, esterified cholesterol in LDL, and HDL fraction of total lipoprotein particle number.
  • Ratio-driven clustering, integrated cellular assays, and mouse studies to investigate gene functions and pathways.

Main Results:

  • Identified new ratio-based markers for LPmtr pathways, linking genetic loci to specific biological functions.
  • Discovered potential causal genes at poorly characterized lipid risk loci.
  • Demonstrated the utility of lipoprotein fine-mapping for generating drug target hypotheses and uncovering hyperlipidemia mechanisms.
  • Implicated miR-148 in TG secretion and ER-stress responses, linking them to VLDL metabolism via mTORC1.
  • Identified miR-148a as a determinant of Lp(a) levels.

Conclusions:

  • Lipoprotein fine-mapping using metabolomic data and GWAS provides novel insights into lipoprotein particle biology.
  • Assessing lipoprotein size and composition is crucial for understanding, preventing, and treating lipid-related disorders.
  • The study generates new hypotheses for drug target development in cardiovascular disease and hyperlipidemia.