Liquid Chromatography Coupled To Mass Spectrometry Reveals That Aging Affects Lipid Droplet Composition

Abstract

Lipid droplets (LD) are intracellular organelles controlling neutral lipid metabolism and storage. One of the recently discovered functions of LDs is the essential role they play in aging process. Alterations in membrane lipid composition are one of the major changes that are shown to take place in many of the aging models. An increase in cholesterol to phospholipid ratio was reported in rat models of aging. A reduction in the level of polyunsaturated fatty acyl is the next important age related variable observed in these aging systems. However, there is no systematic report characterizing the lipid composition of lipid droplets in aging models including Caenorhabditis elegans and mouse liver tissue. In this thesis, ultra-high performance liquid chromatography coupled to mass spectrometry techniques were used to characterize the composition of lipid droplets. The performances of two high resolution mass spectrometers were compared with regards to detection and identification of small hydrophobic molecules. Different software packages and bioinformatics tools were compared to discover possible variation of the extracted information. The selected mass spectrometry platform and optimized data analysis workflow were used to study lipid droplets and identify candidate biomarkers of aging. Preliminary identifications made here could potentially be used as biomarkers in aging diseases and could ultimately lead to treatments for age-related disorders.