RESUMEN
Circulating phospholipids have been considered as biomarkers and therapeutic targets in multiple disorders. Atopic dermatitis (AD) is the most common inflammatory skin disease. Although there are numerous studies having addressed stratum corneum lipids in the context of epidermal barrier, little is known about the circulating lipids in patients with AD. In this study, we explored the changes of serum phospholipids in AD using liquid chromatography coupled to tandem mass spectrometry and sought serum lipids' contribution to clinical status. Several serum levels of phospholipids were altered in the AD group (n = 179) compared with that in healthy controls (n = 47) and patients without AD with atopic comorbidities (n = 22); lipids exhibiting the apparent changes included increased sphingosine, multiple variants of phosphatidylcholine, and decreased ceramide (16:0) in patients with AD. Moreover, serum levels of sphingosine correlated with the severity of AD, and sphingosine and ceramide(16:0) were also detected as the risk-increasing effect and risk-reduction effect of AD, respectively. In summary, alterations in the serum concentration of phospholipids are seen in patients with AD. Although more detailed investigations will be needed to evaluate the significance of the changes in circulating lipids in AD, these findings can provide, to our knowledge, previously unreported insight into AD's pathogenesis and therapeutic strategies.
RESUMEN
Lysophosphatidylcholine (LPC) has been widely used as emulsifier in animal feeds to enhance the lipid utilization. However, the effects of LPC on fillet quality has rarely been known. The present study was the first time to investigate the response of fish muscle lipidomics to dietary LPC supplementation. Turbot muscle samples were collected after a 56-day feeding trial where the experimental diet contained 0 or 0.25% LPC. Targeted tandem mass spectrometry was used in the lipidomic analysis. A total of 62 individual lipids (58 up-regulated and 7 down-regulated by LPC) showed significant difference in concentration in response to dietary LPC. Most of these differentially abundant lipids were diacylglycerol, free fatty acid and cardiolipin, and they all were up-regulated by dietary LPC. However, LPC exerted only marginal effects on muscle fatty acid composition and lipid content. The effects of dietary LPC on fillet lipid composition cannot be neglected in fish product evaluation.
RESUMEN
The sphingolipid de novo synthesis pathway, encompassing the sphingolipids, the enzymes and the cell membrane receptors, are being investigated for their role in diseases and as potential therapeutic targets. The intermediate sphingolipids such as dihydrosphingosine (dhSph) and sphingosine (Sph) have not been investigated due to them being thought of as precursors to other more active lipids such as ceramide (Cer) and sphingosine 1 phosphate (S1P). Here we investigated their effects in terms of collagen synthesis in primary rat neonatal cardiac fibroblasts (NCFs). Our results in NCFs showed that both dhSph and Sph did not induce collagen synthesis, whilst dhSph reduced collagen synthesis induced by transforming growth factor ß (TGFß). The mechanisms of these inhibitory effects were associated with the increased activation of the de novo synthesis pathway that led to increased dihydrosphingosine 1 phosphate (dhS1P). Subsequently, through a negative feedback mechanism that may involve substrate-enzyme receptor interactions, S1P receptor 1 expression (S1PR1) was reduced.
RESUMEN
In host-microbe interactions, signaling lipids function in interpartner communication during both the establishment and maintenance of associations. Previous evidence suggests that sphingolipids play a role in the mutualistic cnidarian-Symbiodinium symbiosis. Exogenously applied sphingolipids have been shown to alter this partnership, though endogenous host regulation of sphingolipids by the sphingosine rheostat under different symbiotic conditions has not been characterized. The rheostat regulates levels of pro-survival sphingosine-1-phosphate (S1P) and pro-apoptotic sphingosine (Sph) through catalytic activities of sphingosine kinase (SPHK) and S1P phosphatase (SGPP). The role of the rheostat in recognition and establishment of cnidarian-Symbiodinium symbiosis was investigated in the sea anemone Aiptasia pallida by measuring gene expression, protein levels, and sphingolipid metabolites in symbiotic, aposymbiotic, and newly recolonized anemones. Comparison of two host populations showed that symbiotic animals from one population had lower SGPP gene expression and Sph lipid concentrations compared to aposymbiotic animals, while the other population had higher S1P concentrations than their aposymbiotic counterparts. In both populations, the host rheostat trended toward host cell survival in the presence of symbionts. Furthermore, upregulation of both rheostat enzymes on the first day of host recolonization by symbionts suggests a role for the rheostat in host-symbiont recognition during symbiosis onset. Collectively, these data suggest a regulatory role of sphingolipid signaling in cnidarian-Symbiodinium symbiosis and symbiont uptake.
Asunto(s)
Dinoflagelados/fisiología , Anémonas de Mar/fisiología , Esfingolípidos/metabolismo , Simbiosis , Animales , Dinoflagelados/genética , Regulación de la Expresión Génica , Anémonas de Mar/parasitologíaRESUMEN
Bioactive sphingolipids including ceramides are involved in a variety of pathophysiological processes by regulating cell death and survival. The objective of the current study was to examine ceramide metabolism in preeclampsia, a serious disorder of pregnancy characterized by oxidative stress, and increased trophoblast cell death and autophagy. Maternal circulating and placental ceramide levels quantified by tandem mass spectrometry were elevated in pregnancies complicated by preeclampsia. Placental ceramides were elevated due to greater de novo synthesis via high serine palmitoyltransferase activity and reduced lysosomal breakdown via diminished ASAH1 expression caused by TGFB3-induced E2F4 transcriptional repression. SMPD1 activity was reduced; hence, sphingomyelin degradation by SMPD1 did not contribute to elevated ceramide levels in preeclampsia. Oxidative stress triggered similar changes in ceramide levels and acid hydrolase expression in villous explants and trophoblast cells. MALDI-imaging mass spectrometry localized the ceramide increases to the trophophoblast layers and syncytial knots of placentae from pregnancies complicated by preeclampsia. ASAH1 inhibition or ceramide treatment induced autophagy in human trophoblast cells via a shift of the BOK-MCL1 rheostat toward prodeath BOK. Pharmacological inhibition of ASAH1 activity in pregnant mice resulted in increased placental ceramide content, abnormal placentation, reduced fetal growth, and increased autophagy via a similar shift in the BOK-MCL1 system. Our results reveal that oxidative stress-induced reduction of lysosomal hydrolase activities in combination with elevated de novo synthesis leads to ceramide overload, resulting in increased trophoblast cell autophagy, and typifies preeclampsia as a sphingolipid storage disorder.