Fluorescence-based fixative and vital staining of lipid droplets in Caenorhabditis elegans reveal fat stores using microscopy and flow cytometry approaches

J Lipid Res. 2011 Jun;52(6):1281-1293. doi: 10.1194/jlr.D011940. Epub 2011 Mar 18.

Abstract

The proportions of body fat and fat-free mass are determining factors of adiposity-associated diseases. Work in Caenorhabditis elegans has revealed evolutionarily conserved pathways of fat metabolism. Nevertheless, analysis of body composition and fat distribution in the nematodes has only been partially unraveled because of methodological difficulties. We characterized metabolic C. elegans mutants by using novel and feasible BODIPY 493/503-based fat staining and flow cytometry approaches. Fixative as well as vital BODIPY staining procedures visualize major fat stores, preserve native lipid droplet morphology, and allow quantification of fat content per body volume of individual worms. Colocalization studies using coherent anti-Stokes Raman scattering microscopy, Raman microspectroscopy, and imaging of lysosome-related organelles as well as biochemical measurement confirm our approaches. We found that the fat-to-volume ratio of dietary restriction, TGF-β, and germline mutants are specific for each strain. In contrast, the proportion of fat-free mass is constant between the mutants, although their volumes differ by a factor of 3. Our approaches enable sensitive, accurate, and high-throughput assessment of adiposity in large C. elegans populations at a single-worm level.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / chemistry
  • Adipose Tissue / metabolism*
  • Adiposity*
  • Animals
  • Azo Compounds / analysis
  • Boron Compounds / analysis
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / metabolism*
  • Disease Models, Animal
  • Fixatives / analysis
  • Fixatives / metabolism
  • Flow Cytometry
  • Fluorescence
  • Germ-Line Mutation
  • High-Throughput Screening Assays*
  • Lipid Metabolism
  • Microscopy
  • Obesity / metabolism*
  • Species Specificity
  • Spectrum Analysis, Raman
  • Staining and Labeling / methods*
  • Transforming Growth Factor beta / analysis
  • Transforming Growth Factor beta / biosynthesis

Substances

  • 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene
  • Azo Compounds
  • Boron Compounds
  • Fixatives
  • Transforming Growth Factor beta
  • oil red O