Quantitative lipidomic analysis of mouse lung during postnatal development by electrospray ionization tandem mass spectrometry

Abstract

Lipids play very important roles in lung biology, mainly reducing the alveolar surface tension at the air-liquid interface thereby preventing end-expiratory collapse of the alveoli. In the present study we performed an extensive quantitative lipidomic analysis of mouse lung to provide the i) total lipid quantity, ii) distribution pattern of the major lipid classes, iii) composition of individual lipid species and iv) glycerophospholipid distribution pattern according to carbon chain length (total number of carbon atoms) and degree of unsaturation (total number of double bonds). We analysed and quantified 160 glycerophospholipid species, 24 sphingolipid species, 18 cholesteryl esters and cholesterol from lungs of a) newborn (P1), b) 15-day-old (P15) and c) 12-week-old adult mice (P84) to understand the changes occurring during postnatal pulmonary development. Our results revealed an increase in total lipid quantity, correlation of lipid class distribution in lung tissue and significant changes in the individual lipid species composition during postnatal lung development. Interestingly, we observed significant stage-specific alterations during this process. Especially, P1 lungs showed high content of monounsaturated lipid species; P15 lungs exhibited myristic and palmitic acid containing lipid species, whereas adult lungs were enriched with polyunsaturated lipid species. Taken together, our study provides an extensive quantitative lipidome of the postnatal mouse lung development, which may serve as a reference for a better understanding of lipid alterations and their functions in lung development and respiratory diseases associated with lipids.

Hyperoxic Exposure Caused Lung Lipid Compositional Changes in Neonatal Mice

“…LPC (16:0) and LPC (22:6) were increased at pnd14 compared to those at pnd7 in normoxic exposure, which agrees with their continuous increase during lung development [ 12 ]. Neonatal hyperoxia has been shown to increase the levels of phospholipases A2 in mouse lungs [ 20 ].…”

“…There are a few studies showing compositional changes in the lipidome during postnatal lung development in mice and humans [ 11 , 12 , 16 , 17 , 18 ]. Whether neonatal hyperoxia alters this lung lipid profile in mice remains unclear.…”

“…In general, the amounts of lung glycerophospholipids (PC, PE, PG, PI, and PS) are significantly reduced in adult mice compared to those in neonatal mice (pnd7 and pnd14) [ 11 ]. Levels of certain glycerophospholipid species are also altered from the saccular phase to the alveolar stages [ 11 , 12 ]. This is corroborated by increased glycerophospholipids of pulmonary tissue at pnd14 compared to those at pnd7.…”

“…A previous study has identified 924 unique lipids across 21 lipid subclasses in lungs from postnatal day (pnd) 7, pnd14, and adult mice, with dramatic alterations in the lipidome across developmental stages using lipidomics analysis [ 11 ]. For instance, a high content of monounsaturated lipid species is observed in lungs from mice at pnd1; myristic and palmitic acid-containing lipid species are present in lungs at pnd15, whereas adult lungs are enriched with polyunsaturated lipid species [ 12 ]. Although hyperoxic exposure decreases cellular content of monounsaturated and polyunsaturated fatty acids but increases levels of saturated fatty acids in cultured tracheal epithelial cells [ 13 ], there are no reports regarding whether neonatal hyperoxia changes lipid profiles in mouse lungs.…”

High-resolution atmospheric-pressure MALDI mass spectrometry imaging workflow for lipidomic analysis of late fetal mouse lungs

“…of the lungs in diseased states, during fetal and postnatal stages, is a key to understand the molecular alterations during lung development and the pathogenesis or pathophysiology of various pulmonary diseases, associated with these indispensable biomolecules 49,50 . We recently reported significant stage-specific differences in the individual lipid-species composition of mouse lung during postnatal pulmonary development processes 49 . However, so far no information is available on the lipidome of fetal mouse lungs, from either MSI or liquid chromatography-mass spectrometry.…”