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- Burla, Bo, et al.
(författare)
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MS-based lipidomics of human blood plasma : a community-initiated position paper to develop accepted guidelines
- 2018
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Ingår i: Journal of Lipid Research. - : American Society for Biochemistry and Molecular Biology. - 0022-2275 .- 1539-7262. ; 59:10, s. 2001-2017
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Tidskriftsartikel (refereegranskat)abstract
- Human blood is a self-regenerating lipid-rich biological fluid that is routinely collected in hospital settings. The inventory of lipid molecules found in blood plasma (plasma lipidome) offers insights into individual metabolism and physiology in health and disease. Disturbances in the plasma lipidome also occur in conditions that are not directly linked to lipid metabolism; therefore, plasma lipidomics based on MS is an emerging tool in an array of clinical diagnostics and disease management. However, challenges exist in the translation of such lipidomic data to clinical applications. These relate to the reproducibility, accuracy, and precision of lipid quantitation, study design, sample handling, and data sharing. This position paper emerged from a workshop that initiated a community-led process to elaborate and define a set of generally accepted guidelines for quantitative MS-based lipidomics of blood plasma or serum, with harmonization of data acquired on different instrumentation platforms across independent laboratories as an ultimate goal. We hope that other fields may benefit from and follow such a precedent.
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| 2. |
- Chaudhari, Aditi, et al.
(författare)
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ARAP2 promotes GLUT1-mediated basal glucose uptake through regulation of sphingolipid metabolism
- 2016
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Ingår i: Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids. - : Elsevier BV. - 1388-1981. ; 1861:11, s. 1643-1651
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Tidskriftsartikel (refereegranskat)abstract
- Lipid droplet formation, which is driven by triglyceride synthesis, requires several droplet-associated proteins. We identified ARAP2 (an ADP-ribosylation factor 6 GTPase-activating protein) in the lipid droplet proteome of NIH-3T3 cells and showed that knockdown of ARAP2 resulted in decreased lipid droplet formation and triglyceride synthesis. We also showed that ARAP2 knockdown did not affect fatty acid uptake but reduced basal glucose uptake, total levels of the glucose transporter GLUT1, and GLUT1 levels in the plasma membrane and the lipid micro-domain fraction (a specialized plasma membrane domain enriched in sphingolipids). Microarray analysis showed that ARAP2 knockdown altered expression of genes involved in sphingolipid metabolism. Because sphingolipids are known to play a key role in cell signaling, we performed lipidomics to further investigate the relationship between ARAP2 and sphingolipids and potentially identify a link with glucose uptake. We found that ARAP2 knockdown increased glucosylceramide and lactosylceramide levels without affecting ceramide levels, and thus speculated that the rate-limiting enzyme in glycosphingolipid synthesis, namely glucosylceramide synthase (GCS), could be modified by ARAP2. In agreement with our hypothesis, we showed that the activity of GCS was increased by ARAP2 knockdown and reduced by ARAP2 overexpression. Furthermore, pharmacological inhibition of GCS resulted in increases in basal glucose uptake, total GLUT1 levels, triglyceride biosynthesis from glucose, and lipid droplet formation, indicating that the effects of GCS inhibition are the opposite to those resulting from ARAP2 knockdown. Taken together, our data suggest that ARAP2 promotes lipid droplet formation by modifying sphingolipid metabolism through GCS.
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| 3. |
- Ekroos, Johan, et al.
(författare)
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Philopatric predisposition to predation-induced ecological traps: habitat-dependent mortality of breeding eiders
- 2012
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Ingår i: Oecologia. - : Springer Science and Business Media LLC. - 1432-1939 .- 0029-8549. ; 170:4, s. 979-986
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Tidskriftsartikel (refereegranskat)abstract
- Because population size is sensitive to changes in adult survival, adult survival may be buffered against environmental variability. Philopatry may be adaptive in changing environments, but it could also constrain breeding habitat selection under changing conditions such as shifting predation regimes. Habitat preference and quality could become decoupled in long-lived philopatric species that evolved in stable environments when suddenly faced by increased adult predation risk, as dispersal may be triggered by past reproductive failure. We evaluated whether the Baltic eider (Somateria m. mollissima) population may currently face a predation-induced ecological trap. Eiders are philopatric and nest on open and forested islands. We hypothesized that open-nesting females would be disproportionately affected by increased predation. We compared female annual survival in these two habitats in 1996-2010. We also tested for effects of time trends, winter severity (NAO), female body condition, and habitat-specific predation pressure on survival. Our results revealed the lowest survival recorded for this species (I broken vertical bar = 0.720), and survival on open islands was significantly lower (I broken vertical bar = 0.679) than on forested islands (I broken vertical bar = 0.761). Nonetheless, only 0.7 % of females changed breeding habitat type despite ample availability of alternative islands, and breeding phenology in both habitats was similar. Female survival increased with body condition, while it was unrelated to winter climate and stable over time. Open islands had a higher predation pressure on incubating females. Breeding philopatry results in a predator-mediated ecological trap for open-nesting eiders. Our results contribute to explaining the drastic decline of the Baltic eider population.
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| 7. |
- Perman, Jeanna, 1981, et al.
(författare)
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The VLDL receptor promotes lipotoxicity and increases mortality in mice following an acute myocardial infarction.
- 2011
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Ingår i: The Journal of clinical investigation. - : American Society for Clinical Investigation. - 1558-8238 .- 0021-9738. ; 121:7, s. 2625-40
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Tidskriftsartikel (refereegranskat)abstract
- Impaired cardiac function is associated with myocardial triglyceride accumulation, but it is not clear how the lipids accumulate or whether this accumulation is detrimental. Here we show that hypoxia/ischemia-induced accumulation of lipids in HL-1 cardiomyocytes and mouse hearts is dependent on expression of the VLDL receptor (VLDLR). Hypoxia-induced VLDLR expression in HL-1 cells was dependent on HIF-1α through its interaction with a hypoxia-responsive element in the Vldlr promoter, and VLDLR promoted the endocytosis of lipoproteins. Furthermore, VLDLR expression was higher in ischemic compared with nonischemic left ventricles from human hearts and was correlated with the total lipid droplet area in the cardiomyocytes. Importantly, Vldlr-/- mice showed improved survival and decreased infarct area following an induced myocardial infarction. ER stress, which leads to apoptosis, is known to be involved in ischemic heart disease. We found that ischemia-induced ER stress and apoptosis in mouse hearts were reduced in Vldlr-/- mice and in mice treated with antibodies specific for VLDLR. These findings suggest that VLDLR-induced lipid accumulation in the ischemic heart worsens survival by increasing ER stress and apoptosis.
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| 8. |
- Ståhlman, Marcus, 1975, et al.
(författare)
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Clinical dyslipidaemia is associated with changes in the lipid composition and inflammatory properties of apolipoprotein-B-containing lipoproteins from women with type 2 diabetes.
- 2012
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 1432-0428 .- 0012-186X. ; 55:4, s. 1156-66
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Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis The aim of this study was to use lipidomics to determine if the lipid composition of apolipoprotein-B-containing lipoproteins is modified by dyslipidaemia in type 2 diabetes and if any of the identified changes potentially have biological relevance in the pathophysiology of type 2 diabetes. Methods VLDL and LDL from normolipidaemic and dyslipidaemic type 2 diabetic women and controls were isolated and quantified with HPLC and mass spectrometry. A detailed molecular characterisation of VLDL triacylglycerols (TAG) was also performed using the novel ozone-induced dissociation method, which allowed us to distinguish vaccenic acid (C18:1 n-7) from oleic acid (C18:1 n-9) in specific TAG species. Results Lipid class composition was very similar in VLDL and LDL from normolipidaemic type 2 diabetic and control participants. By contrast, dyslipidaemia was associated with significant changes in both lipid classes (e.g. increased diacylglycerols) and lipid species (e.g. increased C16:1 and C20:3 in phosphatidylcholine and cholesteryl ester and increased C16:0 [palmitic acid] and vaccenic acid in TAG). Levels of palmitic acid in VLDL and LDL TAG correlated with insulin resistance, and VLDL TAG enriched in palmitic acid promoted increased secretion of proinflammatory mediators from human smooth muscle cells. Conclusions We showed that dyslipidaemia is associated with major changes in both lipid class and lipid species composition in VLDL and LDL from women with type 2 diabetes. In addition, we identified specific molecular lipid species that both correlate with clinical variables and are proinflammatory. Our study thus shows the potential of advanced lipidomic methods to further understand the pathophysiology of type 2 diabetes.
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| 9. |
- Yetukuri, Laxman, et al.
(författare)
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Informatics and computational strategies for the study of lipids
- 2008
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Ingår i: Molecular Biosystems. - : Royal Society of Chemistry. - 1742-206X .- 1742-2051. ; 4:2, s. 121-127
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Tidskriftsartikel (refereegranskat)abstract
- Recent advances in mass spectrometry (MS)-based techniques for lipidomic analysis have empowered us with the tools that afford studies of lipidomes at the systems level. However, these techniques pose a number of challenges for lipidomic raw data processing, lipid informatics, and the interpretation of lipidomic data in the context of lipid function and structure. Integration of lipidomic data with other systemic levels, such as genomic or proteomic, in the context of molecular pathways and biophysical processes provides a basis for the understanding of lipid function at the systems level. The present report, based on the limited literature, is an update on a young but rapidly emerging field of lipid informatics and related pathway reconstruction strategies.
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