Abstract
Although the synthesis pathways of intracellular triacylglycerol (TAG) species have been well elucidated, assessment of the contribution of an individual pathway to TAG pools in different mammalian organs, particularly under pathophysiological conditions, is difficult, although not impossible. Herein, we developed and validated a novel bioinformatic approach to assess the differential contributions of the known pathways to TAG pools through simulation of TAG ion profiles determined by shotgun lipidomics. This powerful approach was applied to determine such contributions in mouse heart, liver, and skeletal muscle and to examine the changes of these pathways in mouse liver induced after treatment with a high-fat diet. It was clearly demonstrated that assessment of the altered TAG biosynthesis pathways under pathophysiological conditions can be readily achieved through simulation of lipidomics data. Collectively, this new development should greatly facilitate our understanding of the biochemical mechanisms underpinning TAG accumulation at the states of obesity and lipotoxicity.
Highlights
The synthesis pathways of intracellular triacylglycerol (TAG) species have been well elucidated, assessment of the contribution of an individual pathway to TAG pools in different mammalian organs, under pathophysiological conditions, is difficult, not impossible
Simulated TAG ion profiles were well matched to those experimentally determined utilizing the hypothetical model and lipidomics data with the indicated parameters (Fig. 2). These results indicate that the MAG-DAG pathway (i.e., K2) is the sole or major synthesis pathway contributing to the TAG pool present in mouse skeletal muscle or heart, respectively, while both MAG-DAG and phosphatidic acid (PA)-DAG (i.e., K1) pathways contribute to the TAG pool present in mouse liver (Table 1)
We developed and validated a novel approach for the simulation of the synthesis of TAG species and determined the contributions of individual biosynthesis pathways to the TAG pool using lipidomics data
Summary
The synthesis pathways of intracellular triacylglycerol (TAG) species have been well elucidated, assessment of the contribution of an individual pathway to TAG pools in different mammalian organs, under pathophysiological conditions, is difficult, not impossible. It has remained a challenge to utilize the vast datasets associated with the MDMS-SL platform, e.g., to develop a bioinformatic approach for the interpretation of lipidomic networks of TAG biosynthesis and reveal their association with lipotoxicity under pathophysiological conditions. The development of such an approach would significantly advance the practical use of the platform for investigating the association of altered TAG mass with any (patho)physiological changes
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