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Multiparametric platform for profiling lipid trafficking in human leukocytes.

Simon G Pfisterer1, Ivonne Brock1,2,3, Kristiina Kanerva1,2,3

  • 1Department of Anatomy, Faculty of Medicine, University of Helsinki, Haartmaninkatu 8, 00290 Helsinki, Finland.

Cell Reports Methods
|April 27, 2022
PubMed
Summary

We developed a new imaging platform to measure how cells handle lipids, improving understanding of high cholesterol and related diseases. This method helps differentiate individuals with normal versus high cholesterol levels.

Keywords:
FHLDLLDL uptakeLDLRautomated image analysishigh-content imaginghypercholesterolemialipid dropletobesity

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Area of Science:

  • Biochemistry
  • Cell Biology
  • Medical Diagnostics

Background:

  • Cellular lipid metabolism plays a critical role in metabolic disorders, including hypercholesterolemia.
  • Understanding cellular dysfunction is key to improving disease etiology, risk assessment, and patient stratification.
  • Current methods may not fully capture the dynamic cellular processes involved in lipid handling.

Purpose of the Study:

  • To present a multiparametric high-content imaging platform for quantifying low-density lipoprotein (LDL) uptake and lipid storage in primary leukocytes.
  • To integrate lipid mobilization as a functional readout of cellular lipid metabolism.
  • To assess the platform's utility in differentiating individuals with varying LDL-cholesterol (LDL-c) levels, including familial hypercholesterolemia (FH).

Main Methods:

  • Developed a high-content imaging platform to quantify LDL uptake and lipid droplet storage in leukocyte subpopulations.
  • Integrated lipid mobilization as a measure of cellular lipid depletion efficiency.
  • Validated the platform using samples from 65 individuals with diverse LDL-c levels, including FH and non-FH subjects.

Main Results:

  • The platform successfully quantifies LDL uptake and lipid storage in primary leukocytes.
  • Lipid mobilization correlates positively with LDL uptake and negatively with hypercholesterolemia and age.
  • The combined cell-based readouts and polygenic risk score offer improved explanation of hypercholesterolemia compared to genetic risk alone.

Conclusions:

  • The developed imaging platform provides functional insights into cellular lipid trafficking.
  • This technology can enhance the understanding of metabolic disorders at a cellular level.
  • The platform has broad applications in dissecting the cellular basis of diseases related to lipid metabolism.