BackgroundPrevious lipidomic analyses of the human meibum had largely focused on individuals from non-Asian populations, despite the higher prevalence of dysfunctional tear syndrome (DTS) observed across Asia. Information pertaining to the alterations in lipid profiles in relation to DTS onset and progression is also lacking and warrants comprehensive experimental analysis.Methodologies/Principal FindingsWe examined the meibum lipidome of 27 DTS patients and 10 control subjects for a total of 256 lipid species from 12 major lipid classes, including cholesteryl ester (CE), wax ester (WE), triacylglyceride (TAG), (O-acyl)-ω-hydroxy fatty acid (OAHFA), glycerophospholipids (phosphatidylcholine, PC; phosphatidylethanolamine, PE; phosphatidylinositol, PI; phosphatidylglycerol, PG) and sphingolipids (sphingomyelin, SM; ceramide, Cer; glucosylceramide, GluCer; dihexosylceramide, DihexCer). Neutral lipids were analysed using high-performance liquid-chromatography coupled with mass spectrometry (HPLC/MS) and tandem mass spectrometry (MS/MS) was used for the qualitative and quantitative analysis of polar lipid species. DTS patients were classified into three severity groups (i.e. mild, moderate and severe) based on the ocular surface disease index (OSDI). A significantly lower level of TAG (p<0.05) was observed in patients under the moderate category compared to the mild category. Notably, a number of OAHFA species displayed consistently decreasing levels that correlate with increasing disease severity. An attempt was also made to investigate the changes in meibum lipid profiles of DTS patients compared to normal individuals classified based on OSDI score. Several unsaturated TAG and PC species were found at significantly higher levels (p<0.05) in patients than controls.ConclusionThe current study presents, for the first time, a comprehensive lipidome of meibum from individuals of an Asian ethnicity, which can potentially offer new insights into the higher prevalence of DTS observed amongst Asian populations. This study also represents an attempt towards identification of lipid species in meibum which could serve as marker for DTS.

Lipid levels are commonly used in clinical settings as disease biomarkers, and the advent of mass spectrometry-based (MS) lipidomics heralds the possibility of identifying additional lipids that can inform disease predispositions. However, the degree of natural variation for many lipids remains poorly understood, thus confounding downstream investigations on whether a specific intervention is driving observed lipid fluctuations. Here, we performed targeted mass spectrometry with multiple reaction monitoring across a comprehensive spectrum of 192 plasma lipids on eight subjects across three time-points separated by six hours and two standardized meals. A validation study to confirm the initial discoveries was performed in a further set of nine subjects, subject to the identical study design. Technical variation of the MS was assessed using duplicate measurements in the validation study, while biological variation was measured for lipid species with coefficients of variation <20%. We observed that eight lipid species from the phosphatidylethanolamine and phosphatidylcholine lipid classes were discovered and validated to vary consistently across the three time-points, where the within-subject variance can be up to 1.3-fold higher than between-subject variance. These findings highlight the importance of understanding the range of biological variation in plasma lipids as a precursor to their use in clinical biochemistry.

Objectives: Myocardial infarction (MI)-induced heart failure (HF) is commonly accompanied with profound effects on skeletal muscle. With the process of MI-induced HF, perturbations in skeletal muscle contribute to muscle atrophy. Exercise is viewed as a feasible strategy to prevent muscle atrophy. The aims of this study were to investigate whether exercise could alleviate MI-induced skeletal muscle atrophy via insulin-like growth factor 1 (IGF-1) pathway in mice. Materials and Methods: Male C57/BL6 mice were used to establish the MI model and divided into three groups: sedentary MI group, MI with aerobic exercise group and MI with resistance exercise group, sham-operated group was used as control. Exercise-trained animals were subjected to four-weeks of aerobic exercise (AE) or resistance exercise (RE). Cardiac function, muscle weight, myofiber size, levels of IGF-1 signaling and proteins related to myogenesis, protein synthesis and degradation and cell apoptosis in gastrocnemius muscle were detected. And H2O2-treated C2C12 cells were intervened with recombinant human IGF-1, IGF-1R inhibitor NVP-AEW541 and PI3K inhibitor LY294002 to explore the mechanism. Results：Exercises up-regulated the IGF-1/IGF-1R-phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling, increased the expressions of Pax7, myogenic regulatory factors (MRFs) and protein synthesis, reduced protein degradation and cell apoptosis in MI-mice. In vitro, IGF-1 up-regulated the levels of Pax7 and MRFs, mTOR and P70S6K, reduced MuRF1, MAFbx and inhibited cell apoptosis via IGF-1R-PI3K/Akt pathway. Conclusion: AE and RE, safely and effectively, alleviate skeletal muscle atrophy by regulating the levels of myogenesis, protein degradation and cells apoptosis in mice with MI via activating IGF-1/IGF-1R-PI3K/Akt pathway.