Metabolomics in retinal diseases: an update

Retinal diseases are a leading cause of visual loss and blindness, affecting a significant proportion of the population worldwide and having a detrimental impact on quality of life, with consequent economic burden. The retina is highly metabolically active, and a number of retinal diseases are associated with metabolic dysfunction. To better understand the pathogenesis underlying such retinopathies, new technology has been developed to elucidate the mechanism behind retinal diseases. Metabolomics is a relatively new “omics” technology, which has developed subsequent to genomics, transcriptomics, and proteomics. This new technology can provide qualitative and quantitative information about low-molecular-weight metabolites (M.W. < 1500 Da) in a given biological system, which shed light on the physiological or pathological state of a cell or tissue sample at a particular time point. In this article we provide an extensive review of the application of metabolomics to retinal diseases, with focus on age-related macular degeneration (AMD), diabetic retinopathy (DR), retinopathy of prematurity (ROP), glaucoma, and retinitis pigmentosa (RP)

Metabolomics for Biomarkers of Type 2 Diabetes Mellitus: Advances and Nutritional Intervention Trends

Abstract Metabolic characterization of type 2 diabetes mellitus (T2DM) is crucial for the identification of individuals at risk for developing diabetes and T2DM-related vascular complications as well as for monitoring disease progression. The application of metabolomics to diabetes research may lead to the identification and discovery of diagnostic and prognostic T2DM biomarkers, in addition to elucidating disease pathways. In the present review, we summarize the distinct classes of metabolites that have been proposed as potential biomarkers for progressing stages of T2DM by metabolomic approaches. Several studies have demonstrated that the metabolism of carbohydrates, lipids, and amino acids is considerably altered in prediabetes and continue to vary over the course of T2DM progression. The identification of intermediate metabolites involved in glycolysis, gluconeogenesis, the tricarboxylic acid cycle, lipolysis, and proteolysis have provided evidence of these metabolic dysfunctions. Finally, given the increasing worldwide incidence of T2DM and its related complications, research should focus on the impact of lifestyle factors, particularly diet, at the metabolomic level for better understanding and improved healthcare strategie

Multi-Omics Integrative Approach of Extracellular Vesicles: A Future Challenging Milestone

In the era of multi-omic sciences, dogma on singular cause-effect in physio-pathological processes is overcome and system biology approaches have been providing new perspectives to see through. In this context, extracellular vesicles (EVs) are offering a new level of complexity, given their role in cellular communication and their activity as mediators of specific signals to target cells or tissues. Indeed, their heterogeneity in terms of content, function, origin and potentiality contribute to the cross-interaction of almost every molecular process occurring in a complex system. Such features make EVs proper biological systems being, therefore, optimal targets of omic sciences. Currently, most studies focus on dissecting EVs content in order to either characterize it or to explore its role in various pathogenic processes at transcriptomic, proteomic, metabolomic, lipidomic and genomic levels. Despite valuable results being provided by individual omic studies, the categorization of EVs biological data might represent a limit to be overcome. For this reason, a multi-omic integrative approach might contribute to explore EVs function, their tissue-specific origin and their potentiality. This review summarizes the state-of-the-art of EVs omic studies, addressing recent research on the integration of EVs multi-level biological data and challenging developments in EVs origin

Tear fluid biomarkers in ocular and systemic disease: potential use for predictive, preventive and personalised medicine

In the field of predictive, preventive and personalised medicine, researchers are keen to identify novel and reliable ways to predict and diagnose disease, as well as to monitor patient response to therapeutic agents. In the last decade alone, the sensitivity of profiling technologies has undergone huge improvements in detection sensitivity, thus allowing quantification of minute samples, for example body fluids that were previously difficult to assay. As a consequence, there has been a huge increase in tear fluid investigation, predominantly in the field of ocular surface disease. As tears are a more accessible and less complex body fluid (than serum or plasma) and sampling is much less invasive, research is starting to focus on how disease processes affect the proteomic, lipidomic and metabolomic composition of the tear film. By determining compositional changes to tear profiles, crucial pathways in disease progression may be identified, allowing for more predictive and personalised therapy of the individual. This article will provide an overview of the various putative tear fluid biomarkers that have been identified to date, ranging from ocular surface disease and retinopathies to cancer and multiple sclerosis. Putative tear fluid biomarkers of ocular disorders, as well as the more recent field of systemic disease biomarkers, will be shown

Lipidomic signatures from physically frail and robust older adults at hospital admission

Identifying serum biomarkers that can predict physical frailty in older adults would have tremendous clinical value for primary care, as this condition is inherently related to poor quality of life and premature mortality. We compared the serum lipid profile of physically frail and robust older adults to identify specific lipid biomarkers that could be used to assess physical frailty in older patients at hospital admission. Forty-three older adults (58.1% male), mean (range) age 86.4 (78–100 years) years, were classified as physically frail (n = 18) or robust (n = 25) based on scores from the Short Physical Performance Battery (≤ 6 points). Non-targeted metabolomic study by ultra-high performance liquid chromatography coupled to mass spectrometry (UHPLC-MS) analysis with later bioinformatics data analysis. Once the significantly different metabolites were identified, the KEGG database was used on them to establish which were the metabolic pathways mainly involved. Area under receiver-operating curve (AUROC) analysis was used to test the discriminatory ability of lipid biomarkers for frailty based on the Short Physical Performance Battery. We identified a panel of five metabolites including ceramides Cer (40:2), Cer (d18:1/20:0), Cer (d18:1/23:0), cholesterol, and hosphatidylcholine (PC) (14:0/20:4) that were significantly increased in physically frail older adults compared with robust older adults at hospital admission. The most interesting in the physically frail metabolome study found with the KEGG database were the metabolic pathways, vitamin digestion and absorption, AGE-RAGE signaling pathway in diabetic complications, and insulin resistance. In addition, Cer (40:2) (AUROC 0.747), Cer (d18:1/23:0) (AUROC 0.720), and cholesterol (AUROC 0.784) were identified as higher values of physically frail at hospital admission. The non-targeted metabolomic study can open a wide view of the physically frail features changes at the plasma level, which would be linked to the physical frailty phenotype at hospital admission. Also, we propose that metabolome analysis will have a suitable niche in personalized medicine for physically frail older adults.Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. This study was funded by a Gobierno de Navarra project Resolución grant 2186/2014 and acknowledged with the 'Beca Ortiz de Landázuri' as the best research clinical project in 2014, as well as by a research grant PI17/01814 of the Ministerio de Economía, Industria y Competitividad (ISCIII, FEDER). A.G.-H. is a Miguel Servet Fellow (Instituto de Salud Carlos III – CP18/0150). N.M.-V. received funding from 'la Caixa' Foundation (ID 100010434), under agreement LCF/PR/PR15/51100006. R.R.-V. is funded in part by a Postdoctoral Fellowship Resolution ID 420/2019 of the Universidad Pública de Navarra

Berberine Could Ameliorate Cardiac Dysfunction via Interfering Myocardial Lipidomic Profiles in the Rat Model of Diabetic Cardiomyopathy

Background: Diabetic cardiomyopathy (DCM) is considered to be a distinct clinical entity independent of concomitant macro- and microvascular disorders, which is initiated partly by disturbances in energy substrates. This study was to observe the dynamic modulations of berberine in DCM rats and explore the changes of lipidomic profiles of myocardial tissue.Methods: Sprague-Dawley (SD) rats were fed high-sucrose and high-fat diet (HSHFD) for totally 22 weeks and intraperitoneally (i.p.) injected with 30 mg/kg of streptozotocin (STZ) at the fifth week to induce DCM. Seventy-two hours after STZ injection, the rats were orally given with berberine at 10, 30 mg/kg and metformin at 200 mg/kg, respectively. Dynamic changes of cardiac function, heart mass ratios and blood lipids were observed at f 4, 10, 16, and 22, respectively. Furthermore, lipid metabolites in myocardial tissue at week 16 were profiled by the ultra-high-performance liquid chromatography coupled to a quadruple time of flight mass spectrometer (UPLC/Q-TOF/MS) approach.Results: Berberine could protect against cardiac diastolic and systolic dysfunctions, as well as cardiac hypertrophy, and the most effective duration is with 16-week of administration. Meanwhile, 17 potential biomarkers of phosphatidylcholines (PCs), phosphatidylethanolamines (PEs) and sphingolipids (SMs) of DCM induced by HSFD/STZ were identified. The perturbations of lipidomic profiles could be partly reversed with berberine intervention, i.e., PC (16:0/20:4), PC (18:2/0:0), PC (18:0/18:2), PC (18:0/22:5), PC (20:4/0:0), PC (20:4/18:0), PC (20:4/18:1), PC (20:4/20:2), PE (18:2/0:0), and SM (d18:0/16:0).Conclusions: These results indicated a close relationship between PCs, PEs and SMs and cardiac damage mechanisms during development of DCM. The therapeutic effects of berberine on DCM are partly caused by interferences with PCs, PEs, and SMs metabolisms

Lipidomic signatures from physically frail and robust older adults at hospital admission

Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. This study was funded by a Gobierno de Navarra project Resolucion grant 2186/2014 and acknowledged with the "Beca Ortiz de Landazuri" as the best research clinical project in 2014, as well as by a research grant PI17/01814 of the Ministerio de Economia, Industria y Competitividad (ISCIII, FEDER). A.G.-H. is a Miguel Servet Fellow (Instituto de Salud Carlos III -CP18/0150). N.M.-V. received funding from "la Caixa" Foundation (ID 100010434), under agreement LCF/PR/PR15/51100006. R.R.-V. is funded in part by a Postdoctoral Fellowship Resolution ID 420/2019 of the Universidad Publica de Navarra.Identifying serum biomarkers that can predict physical frailty in older adults would have tremendous clinical value for primary care, as this condition is inherently related to poor quality of life and premature mortality. We compared the serum lipid profile of physically frail and robust older adults to identify specific lipid biomarkers that could be used to assess physical frailty in older patients at hospital admission. Fortythree older adults (58.1% male), mean (range) age 86.4 (78–100 years) years, were classified as physically frail (n = 18) or robust (n = 25) based on scores from the Short Physical Performance Battery (≤ 6 points). Nontargeted metabolomic study by ultra-high performance liquid chromatography coupled to mass spectrometry (UHPLC-MS) analysis with later bioinformatics data analysis. Once the significantly different metabolites were identified, the KEGG database was used on them to establish which were the metabolic pathways mainly involved. Area under receiver-operating curve (AUROC) analysis was used to test the discriminatory ability of lipid biomarkers for frailty based on the Short Physical Performance Battery. We identified a panel of five metabolites including ceramides Cer (40:2), Cer (d18:1/20:0), Cer (d18:1/23:0), cholesterol, and phosphatidylcholine (PC) (14:0/20:4) that were significantly increased in physically frail older adults compared with robust older adults at hospital admission. The most interesting in the physically frail metabolome study found with the KEGG database were the metabolic pathways, vitamin digestion and absorption, AGERAGE signaling pathway in diabetic complications, and insulin resistance. In addition, Cer (40:2) (AUROC 0.747), Cer (d18:1/23:0) (AUROC 0.720), and cholesterol (AUROC 0.784) were identified as higher values of physically frail at hospital admission. The non-targeted metabolomic study can open a wide view of the physically frail features changes at the plasma level, which would be linked to the physical frailty phenotype at hospital admission. Also, we propose that metabolome analysis will have a suitable niche in personalized medicine for physically frail older adults.Gobierno de Navarra project Resolucion grant 2186/2014Spanish Government PI17/01814Instituto de Salud Carlos III III -CP18/0150La Caixa Foundation 100010434 LCF/PR/PR15/51100006Universidad Publica de Navarra 420/2019CRUE-CSIC agreementSpringer Natur