Lipid profiling analyses from mouse models and human infants

Abstract

This protocol outlines a translational lipidomic approach to discover lipid biomarkers that could predict morphometric body and histological organ measurements (e.g., weight and adiposity gains) during specific stages of life (e.g., early life). We describe procedures ranging from animal experimentation and histological analyses to downstream analytical steps through lipid profiling, both in mice and humans. This protocol represents a reliable and versatile approach to translate and validate candidate lipid biomarkers from animal models to a human cohort. For complete details on the use and execution of this protocol, please refer to Olga et al. (2021).

Keywords: Clinical protocol; Health sciences; Mass spectrometry; Metabolism; Metabolomics; Systems biology.

Graphical abstract

Figure 1

Suitable mouse strains for translational lipidomic experiments Illustration of the appropriate mouse strains to mimic human circulated lipoprotein profile that is dominated by VLDL/LDL particles. (A) Wildtype C57BL/6 is not appropriate since apolipoprotein B-containing particles (VLDL/LDL) in this strain are taken up by the liver and cleared from the circulation. (B and C) (B) Meanwhile, ApoE∗3Leiden (C) or Ldlr−/−. (D) Leiden mice (D) can be acceptable since their plasma lipids are confined to VLDL/LDL particles and levels can be increased with HFD. LDL=low-density lipoprotein, VLDL=very low-density lipoprotein, HFD=high-fat diets, WT=wild-type.

Figure 2

Obesogenic diets applicable for mice FFD=fast food diet, HFD=high-fat diet, WAT=white adipose tissue.

Figure 3

Lipid metabolism pathways