Lipid Signatures Research Articles

Lipid signatures of cardiometabolic risk in children and adolescents with obesity.

Lipid signatures of cardiometabolic risk in children and adolescents with obesity.

A global lipid map of severe fever with thrombocytopenia syndrome virus infection reveals glycerophospholipids as novel prognosis biomarkers.

This study systematically investigated the lipid landscape profile of SFTS-infected patients with different clinical outcomes. Our results revealed a global alteration in the lipid signature, particularly the glycerophospholipid metabolic pathway, induced by SFTSV infection. Notably, LysoPC (20:0) and LysoPC (P-16:0) presented remarkable prognostic value as novel biomarkers for SFTSV infection and may contribute to the prognosis of SFTS progression and appropriate interventions.

Structural diversity of Alzheimer-related protein aggregations revealed using photothermal ratio-metric micro-spectroscopy

The crucial link between pathological protein aggregations and lipids in Alzheimer’s disease pathogenesis is increasingly recognized, yet its spatial dynamics remain challenging for labeling-based microscopy. Here, we demonstrate photothermal ratio-metric infrared spectro-microscopy (PRISM) to investigate the in situ structural and molecular compositions of pathological features in brain tissues at submicron resolution. By identifying the vibrational spectroscopic signatures of protein secondary structures and lipids, PRISM tracks the structural dynamics of pathological proteins, including amyloid and hyperphosphorylated Tau (pTau). Amyloid-associated lipid features in major brain regions were observed, notably the enrichment of lipid-dissociated plaques in the hippocampus. Spectroscopic profiling of pTau revealed significant heterogeneity in phosphorylation levels and a distinct lipid-pTau relationship that contrasts with the anticipated lipid-plaque correlation. Beyond in vitro studies, our findings provide direct visualization evidence of aggregate-lipid interactions across the brain, offering new insights into mechanistic and therapeutic research of neurodegenerative diseases.

Differential Lipid Signatures of Lumbar and Cisternal Cerebrospinal Fluid

Background: The molecular composition of cerebrospinal fluid (CSF) is often used as a key indicator of biochemical alterations within distinct brain and spinal cord fluid compartments. The CSF protein content in lumbar CSF samples is widely employed as a biomarker matrix for diagnosing brain-related pathological conditions. CSF lipid profiles may serve as promising complementary diagnostics, but it remains unresolved if the lipid distribution is consistent along the neuroaxis. Methods: The lipid composition was determined with liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) in cisternal CSF obtained from healthy subjects undergoing preventive surgery of an unruptured aneurism (n = 11) and lumbar CSF obtained from individuals referred for the clinical evaluation of cognitive dysfunction but subsequently cleared and deemed healthy (n = 19). Results: We reveal discernible variations in lipid composition along the neuroaxis, with a higher overall lipid concentration in cisternal CSF, although with different relative distributions of the various lipid classes in the two compartments. The cisternal CSF contained elevated levels of most lipid classes, e.g., sphingomyelins, lysophosphatidylcholines, plasmenylphosphatidylcholines, phosphatidic acids, and triacylglycerols, whereas a few select lipids from the classes of fatty acids, phosphatidylcholines, amides and plasmenylphosphatidylethanolamines were, oppositely, elevated in the lumbar CSF pool. Conclusions: The distinct lipid distribution along the neuroaxis illustrates that the molecular constituents in these two CSF compartments are not uniform. These findings emphasize the necessity of establishing a lumbar lipid index for the accurate interpretation of the cranial CSF lipid profile.

Assessment of the concomitant action of XBD173 and interferon β in a mouse model of multiple sclerosis using infrared marker bands

Disease modifying therapies including interferon-β (IFNβ) effectively counteract the inflammatory component in relapsing-remitting multiple sclerosis (RRMS) but this action, generally associated with severe side effects, does not prevent axonal/neuronal damages. Hence, axonal neuroprotection, which is pivotal for MS effective treatment, remains a difficult clinical challenge. Growing evidence suggested as promising candidate for neuroprotection, Emapunil (AC-5216) or XBD173, a ligand of the mitochondrial translocator protein highly expressed in glial cells and neurons. Indeed, elegant studies previously showed that low and well tolerated doses of XBD173 efficiently improved clinical symptoms and neuropathological markers in MS mice. Here we combined clinical scoring in vivo with Fourier transform infrared spectroscopy of sera samples to investigate the hypothesis that the concomitant treatment of RRMS mice with low doses of IFNβ and XBD173 may increase their beneficial effects against MS symptoms and additionally decrease IFNβ-induced side effects. Our results show a significant alteration of the composition of serum protein and lipids in the spectra of the sera of RRMS mice. While the signature of proteins remains altered upon treatment, the signature of lipids is recovered comparatively well with 20 kIU IFNβ and upon concomitant treatment with a low dose of XBD173 (10 mg/kg) and IFNβ (10 kIU), but not with 10 kIU of IFNβ alone. The concomitant therapy with XBD173 (10 mg/kg) and IFNβ (10 kIU), devoid of side effects, exhibited at least equal or even better efficacy than IFNβ (20 kIU) treatment against RRMS symptoms.

Leveraging ML for profiling lipidomic alterations in breast cancer tissues: a methodological perspective

In this study, a comprehensive methodology combining machine learning and statistical analysis was employed to investigate alterations in the metabolite profiles, including lipids, of breast cancer tissues and their subtypes. By integrating biological and machine learning feature selection techniques, along with univariate and multivariate analyses, a notable lipid signature was identified in breast cancer tissues. The results revealed elevated levels of saturated and monounsaturated phospholipids in breast cancer tissues, consistent with external validation findings. Additionally, lipidomics analysis in both the original and validation datasets indicated lower levels of most triacylglycerols compared to non-cancerous tissues, suggesting potential alterations in lipid storage and metabolism within cancer cells. Analysis of cancer subtypes revealed that levels of PC 30:0 were relatively reduced in HER2(−) samples that were ER(+) and PR(+) compared to those that were ER(−) and PR(−). Conversely, HER2(+) tumors, which were ER(−) and PR(−), exhibited increased concentrations of PC 30:0. This increase could potentially be linked to the role of Stearoyl-CoA-Desaturase 1 in breast cancer. Comprehensive metabolomic analyses of breast cancer can offer crucial insights into cancer development, aiding in early detection and treatment evaluation of this devastating disease.

Urinary biochemical ecology reveals microbiome-metabolite interactions and metabolic markers of recurrent urinary tract infection.

Recurrent urinary tract infections (rUTIs) are a major clinical challenge in postmenopausal women and their increasing prevalence underscores the need to define interactions between the host and the urinary microbiome that may underlie rUTI susceptibility. A body of work has identified the taxonomic profile of the female urinary microbiome associate with aging, menopause, and urinay disease. However, how this microbial community engages with the host niche, including the local biochemical environment of the urogenital tract, in health and disease is yet to be fully defined. This study directly assesses differences in the biochemical environment of the urine, or biochemical ecology, associated with recurrent urinary tract infection (UTI) and defines a microbe-metabolite association network of the female urinary microbiome. By integrating metagenomic and metabolomic data collected from a controlled cohort of women with rUTI, we find that distinct metabolites, such as methionine sulfoxide (Met-SO) and trimethylamine oxide (TMAO), are associated with differences in urinary microbiome diversity. We observe associations between microbial and biochemical beta diversity and unique metabolic networks of uropathogenic Escherichia coli and uroprotective Lactobacillus species, highlighting potential metabolite-driven ecological shifts that may influence UTI susceptibility. We identify a urinary lipid signature of active rUTI that can accurately distinguish (AUC = 0.987) cases controls. Finally, using time-to-relapse data we identify deoxycholic acid (DCA) as a new prognostic indicator for rUTI recurrence. Together these findings suggest that systemic metabolic processes may influence susceptibility, opening new avenues for therapeutic intervention and the development of more accurate diagnostic and prognostic to improve patient outcomes.

A lipid signature of BAK-driven apoptotic pore formation.

Apoptotic cell death is regulated by the BCL-2 protein family, with clusters of BAK or BAX homodimers driving pore formation in the mitochondrial outer membrane via a poorly understood process. There is growing evidence that, in addition to BAK and BAX, lipids play an important role in pore formation. Towards a better understanding of the lipidic drivers of apoptotic pore formation in isolated mitochondria, two complementary approaches were taken. Firstly, the lipids released during BAK-mediated pore formation were measured with targeted lipidomics, revealing enrichment of long chain polyunsaturated lysophospholipids (LPLs) in the released fraction. In contrast, the BAK protein was not released suggesting that BAK and LPLs locate to distinct microdomains. Secondly, added cholesterol not only prevented pore formation but prevented the clustering of BAK homodimers. Our data lead us to a model in which BAK clustering triggers formation of a separate microdomain rich in LPLs that can progress to lipid shedding and the opening of a lipid-lined pore. Pore stabilisation and growth may be due to BAK dimers then moving to the pore edge. Our BAK-lipid microdomain model supports the heterogeneity of BAK assemblies, and the observed lipid-release signature gives new insight into the genesis of the apoptotic pore.

Identification of tauopathy-associated lipid signatures in Alzheimer’s disease mouse brain using label-free chemical imaging

There is cumulative evidence that lipid metabolism plays a key role in the pathogenesis of various neurodegenerative disorders including Alzheimer’s disease (AD). Visualising lipid content in a non-destructive label-free manner can aid in elucidating the AD phenotypes towards a better understanding of the disease. In this study, we combined multiple optical molecular-specific methods, Fourier transform infrared (FTIR) spectroscopic imaging, synchrotron radiation-infrared (SR-IR) microscopy, Raman and stimulated Raman scattering (SRS) microscopy, and optical-photothermal infrared (O-PTIR) microscopy with multivariate data analysis, to investigate the biochemistry of brain hippocampus in situ using a mouse model of tauopathy (rTg4510). We observed a significant difference in the morphology and lipid content between transgenic (TG) and wild type (WT) samples. Immunohistochemical staining revealed some degree of microglia co-localisation with elevated lipids in the brain. These results provide new evidence of tauopathy-related dysfunction in a preclinical study at a subcellular level.

Plasma Lipidomics Reveals Lipid Signatures of Early Pregnancy in Mares

Understanding the systemic biochemistry of early pregnancy in the mare is essential for developing new diagnostics and identifying causes for pregnancy loss. This study aimed to elucidate the dynamic lipidomic changes occurring during the initial stages of equine pregnancy, with a specific focus on days 7 and 14 post-ovulation. By analysing and comparing the plasma lipid profiles of pregnant and non-pregnant mares, the objective of this study was to identify potential biomarkers for pregnancy and gain insights into the biochemical adaptations essential for supporting maternal recognition of pregnancy and early embryonic development. Employing discovery lipidomics, we analysed plasma samples from pregnant and non-pregnant mares on days 7 and 14 post-conception using the SCIEX ZenoTOF 7600 system. This high-resolution mass spectrometry approach enabled us to comprehensively profile and compare the lipidomes across these critical early gestational timepoints. Our analysis revealed significant lipidomic alterations between pregnant and non-pregnant mares and between days 7 and 14 of pregnancy. Key findings include the upregulation of bile acids, sphingomyelins, phosphatidylinositols, and triglycerides in pregnant mares. These changes suggest enhanced lipid synthesis and mobilization, likely associated with the embryo’s nutritional requirements and the establishment of embryo–maternal interactions. There were significant differences in lipid metabolism between pregnant and non-pregnant mares, with a notable increase in the sterol lipid BA 24:1;O5 in pregnant mares as early as day 7 of gestation, suggesting it as a sensitive biomarker for early pregnancy detection. Notably, the transition from day 7 to day 14 in pregnant mares is characterized by a shift towards lipids indicative of membrane biosynthesis, signalling activity, and preparation for implantation. The study demonstrates the profound lipidomic shifts that occur in early equine pregnancy, highlighting the critical role of lipid metabolism in supporting embryonic development. These findings provide valuable insights into the metabolic adaptations during these period and potential biomarkers for early pregnancy detection in mares.

The signature of serum lipids remodeling in recent-onset type 2 diabetes mellitus treated with dulaglutide and liraglutide

The signature of serum lipids remodeling in recent-onset type 2 diabetes mellitus treated with dulaglutide and liraglutide

Unveiling Lipidomic Alterations in Metabolic Syndrome: A Study of Plasma, Liver, and Adipose Tissues in a Dietary-Induced Rat Model

Metabolic syndrome (MetS) is a complex condition characterized by fat accumulation, dyslipidemia, impaired glucose control and hypertension. In this study, rats were fed a high-fat high-fructose (HFF) diet in order to develop MetS. After ten weeks, the dietary-induced MetS was confirmed by higher body fat percentage, lower HDL-cholesterol and increased blood pressure in the HFF-fed rats compared to the normal-fed control animals. However, the effect of MetS development on the lipidomic signature of the dietary-challenged rats remains to be investigated. To reveal the contribution of specific lipids to the development of MetS, the lipid profiling of rat tissues particularly susceptible to MetS was performed using untargeted UHPLC-QTOF-MS/MS lipidomic analysis. A total of 37 lipid species (mainly phospholipids, triglycerides, sphingolipids, cholesterol esters, and diglycerides) in plasma, 43 lipid species in liver, and 11 lipid species in adipose tissue were identified as dysregulated between the control and MetS groups. Changes in the lipid signature of selected tissues additionally revealed systemic changes in the dietary-induced rat model of MetS.

Characterization and biological activity of selenium nanoparticles biosynthesized by Yarrowia lipolytica.

In this research, biogenic selenium nanoparticles were produced by the fungi Yarrowia lipolytica, and the biological activity of its nanoparticles was studied for the first time. The electron microscopy analyses showed the production of nanoparticles were intracellular and the resulting particles were extracted and characterized by XRD, zeta potential, FESEM, EDX, FTIR spectroscopy and DLS. These analyses showed amorphous spherical nanoparticles with an average size of 110 nm and a Zeta potential of -34.51 ± 2.41 mV. Signatures of lipids and proteins were present in the capping layer of biogenic selenium nanoparticles based on FTIR spectra. The antimicrobial properties of test strains showed that Serratia marcescens, Klebsiella pneumonia, Escherichia coli, Pseudomonas aeruginosa and Bacillus subtilis were inhibited at concentrations between 160 and 640 μg/mL, while the growth of Candida albicans was hindered by 80 μg/mL of biogenic selenium nanoparticles. At concentrations between 0.5 and 1.5 mg/mL of biogenic selenium nanoparticles inhibited up to 50% of biofilm formation of Klebsiella pneumonia, Acinetobacter baumannii, Staphylococcus aureus and Pseudomonas aeruginosa. Additionally, the concentration of 20-640 μg/mL of these bioSeNPs showed antioxidant activity. Evaluating the cytotoxicity of these nanoparticles on the HUVEC and HepG2 cell lines did not show any significant toxicity within MIC concentrations of SeNPs. This defines that Y. lipolytica synthesized SeNPs have strong potential to be exploited as antimicrobial agents against pathogens of WHO concern.

A specific serum lipid signature characterizes patients with glycogen storage disease type Ia

Glycogen storage disease type Ia (GSDIa) is a rare, inherited glucose-6-phosphatase-α (G6Pase-α) deficiency-induced carbohydrate metabolism disorder. Although hyperlipidemia is a hallmark of GSDI, the extent of lipid metabolism disruption remains incompletely understood. Lipidomic analysis was performed to characterize the serum lipidome in patients with GSDIa, by including age- and sex-matched healthy controls and age-matched hypercholesterolemic controls. Metabolic control and dietary information biochemical markers were obtained from patients with GSDIa. Patients with GSDIa showed higher total serum lysophosphatidylcholine (Fold Change, (FC) 2.2, P < 0.0001), acyl-acyl-phosphatidylcholine (FC 2.1, P < 0.0001), and ceramide (FC 2.4, P < 0.0001) levels and bile acid (FC 0.7, P < 0.001), acylcarnitines (FC 0.7, P < 0.001), and cholesterol esters (FC 1.0, P < 0.001) than those of healthy controls, and higher di- (FC 1.1, P < 0.0001; FC 0.9, P < 0.01) and triacylglycerol (FC 6.3, P < 0.0001; FC 3.9, P < 0.01) levels than those of healthy controls and hypercholesterolemic subjects. Both total cholesterol and triglyceride values correlated with Cer (d16:1/22:0), Cer (d18:1/20:0), Cer (d18:1/20:0(OH)), Cer (d18:1/22:0), Cer (d18:1/23:0), Cer (d18:1/24:1), Cer (d18:2/22:0), Cer (d18:2/24:1). Total cholesterol also correlated with Cer (d18:1/24:0), Cer (d18:2/20:0), HexCer (d16:1/22:0), HexCer (d18:1/18:0), and Hex2Cer (d18:1/20:0). Triglyceridelevels correlated with Cer (d18:0/24:1). Alanine aminotransferase values correlated with Cer (d18:0/22:0), insulin with Cer (d18:1/22:1) and Cer (d18:1/24:1), and HDL with hexosylceramide (HexCer) (d18:2/23:0). These results expand on the currently known involvement of lipid metabolism in GSDIa. Circulating Cer may allow for refined dietary assessment compared with traditional biomarkers. Because specific lipid species are relatively easy to assess, they represent potential novel biomarkers of GSDIa.

Lipid biochemical diversity and dynamics reveal phytoplankton nutrient-stress responses and carbon export mechanisms in mesoscale eddies in the North Pacific Subtropical Gyre

Mesoscale eddies cause deviations from the background physical and biogeochemical states of the oligotrophic oceans, but how these perturbations manifest in microbial ecosystem functioning, such as community macromolecular composition or carbon export, remains poorly characterized. We present comparative lipidomes from communities entrained in two eddies of opposite polarities (cyclone–anticyclone) in the North Pacific Subtropical Gyre (NPSG). A previous work on this two-eddy system has shown differences in particulate inorganic carbon (PIC) and biogenic silica sinking fluxes between the two eddies despite comparable total organic carbon fluxes. We measured the striking differences between the lipidomes of suspended and sinking particles that indicate taxon-specific responses to mesoscale perturbations. Specifically, cyanobacteria did not appear to respond to increased concentrations of phosphorus in the subsurface of the cyclonic eddy, while eukaryotic microbes exhibit P-stress relief as reflected in their lipid signatures. Furthermore, we found that two classes of lipids drive differences between suspended and sinking material: sinking particles are comparatively enriched in phosphatidylcholine (PC, a membrane-associated lipid) and triacylglycerol (TAG, an energy storage lipid). We observed significantly greater export of TAGs from the cyclonic eddy as compared to the anticyclone and found that this flux is strongly correlated with the concentration of ballast minerals (PIC and biogenic silica). This increased export of TAGs from the cyclone, but not the anticyclone, suggests that cyclonic eddy perturbations may be a mechanism for the delivery of energy-rich organic material below the euphotic zone.

Identifying biochemical changes in the kidney using proton nuclear magnetic resonance in an adenine diet chronic kidney disease mouse model.

This study aimed to investigate the metabolic changes in the kidneys in a murine adenine-diet model of chronic kidney disease (CKD). Kidney fibrosis is the common pathological manifestation across CKD aetiologies. Sustained inflammation and fibrosis cause changes in preferred energy metabolic pathways in the cells of the kidney. Kidney cortical tissue from mice receiving a control or adenine-supplemented diet for 8weeks (late inflammation and fibrosis) and 12 weeks (8weeks of treatment followed by 4weeks recovery) were analysed by 2D-correlated nuclear magnetic resonance spectroscopy and compared with histopathology and biomarkers of kidney damage. Tissue metabolite and lipid levels were assessed using the MestreNova software. Expression of genes related to inflammation, fibrosis, and metabolism were measured using quantitative polymerase chain reaction. Animals showed indicators of severely impaired kidney function at 8 and 12 weeks. Significantly increased fibrosis was present at 8weeks but not in the recovery group suggesting some reversal of fibrosis and amelioration of inflammation. At 8weeks, metabolites associated with glycolysis were increased, while lipid signatures were decreased. Genes involved in fatty acid oxidation were decreased at 8weeks but not 12 weeks while genes associated with glycolysis were significantly increased at 8weeks but not at 12 weeks. In this murine model of CKD, kidney fibrosis was associated with the accumulation of triglyceride and free lactate. There was an up-regulation of glycolytic enzymes and down-regulation of lipolytic enzymes. These metabolic changes reflect the energy demands associated with progressive kidney disease where there is a switch from fatty acid oxidation to that of glycolysis.

Lipid Signatures in Placental Small Extracellular Vesicles define various Hypertensive Disorders of Pregnancy

Lipid Signatures in Placental Small Extracellular Vesicles define various Hypertensive Disorders of Pregnancy

Poration of mitochondrial membranes by amyloidogenic peptides and other biological toxins.

Mitochondria are essential organelles known to serve broad functions, including in cellular metabolism, calcium buffering, signaling pathways and the regulation of apoptotic cell death. Maintaining the integrity of the outer (OMM) and inner mitochondrial membranes (IMM) is vital for mitochondrial health. Cardiolipin (CL), a unique dimeric glycerophospholipid, is the signature lipid of energy-converting membranes. It plays a significant role in maintaining mitochondrial architecture and function, stabilizing protein complexes and facilitating efficient oxidative phosphorylation (OXPHOS) whilst regulating cytochrome c release from mitochondria. CL is especially enriched in the IMM and at sites of contact between the OMM and IMM. Disorders of protein misfolding, such as Alzheimer's and Parkinson's diseases, involve amyloidogenic peptides like amyloid-β, tau and α-synuclein, which form metastable toxic oligomeric species that interact with biological membranes. Electrophysiological studies have shown that these oligomers form ion-conducting nanopores in membranes mimicking the IMM's phospholipid composition. Poration of mitochondrial membranes disrupts the ionic balance, causing osmotic swelling, loss of the voltage potential across the IMM, release of pro-apoptogenic factors, and leads to cell death. The interaction between CL and amyloid oligomers appears to favour their membrane insertion and pore formation, directly implicating CL in amyloid toxicity. Additionally, pore formation in mitochondrial membranes is not limited to amyloid proteins and peptides; other biological peptides, as diverse as the pro-apoptotic Bcl-2 family members, gasdermin proteins, cobra venom cardiotoxins and bacterial pathogenic toxins, have all been described to punch holes in mitochondria, contributing to cell death processes. Collectively, these findings underscore the vulnerability of mitochondria and the involvement of CL in various pathogenic mechanisms, emphasizing the need for further research on targeting CL-amyloid interactions to mitigate mitochondrial dysfunction.

Peripheral Lipid Signatures, Metabolic Dysfunction, and Pathophysiology in Schizophrenia Spectrum Disorders.

Metabolic dysfunction is commonly observed in schizophrenia spectrum disorders (SSDs). The causes of metabolic comorbidity in SSDs are complex and include intrinsic or biological factors linked to the disorder, which are compounded by antipsychotic (AP) medications. The exact mechanisms underlying SSD pathophysiology and AP-induced metabolic dysfunction are unknown, but dysregulated lipid metabolism may play a role. Lipidomics, which detects lipid metabolites in a biological sample, represents an analytical tool to examine lipid metabolism. This systematic review aims to determine peripheral lipid signatures that are dysregulated among individuals with SSDs (1) with minimal exposure to APs and (2) during AP treatment. To accomplish this goal, we searched MEDLINE, Embase, and PsychINFO databases in February 2024 to identify all full-text articles written in English where the authors conducted lipidomics in SSDs. Lipid signatures reported to significantly differ in SSDs compared to controls or in relation to AP treatment and the direction of dysregulation were extracted as outcomes. We identified 46 studies that met our inclusion criteria. Most of the lipid metabolites that significantly differed in minimally AP-treated patients vs. controls comprised glycerophospholipids, which were mostly downregulated. In the AP-treated group vs. controls, the significantly different metabolites were primarily fatty acyls, which were dysregulated in conflicting directions between studies. In the pre-to-post AP-treated patients, the most impacted metabolites were glycerophospholipids and fatty acyls, which were found to be primarily upregulated and conflicting, respectively. These lipid metabolites may contribute to SSD pathophysiology and metabolic dysfunction through various mechanisms, including the modulation of inflammation, cellular membrane permeability, and metabolic signaling pathways.

LC/MS-Based Untargeted Lipidomics Reveals Lipid Signatures of Sarcopenia.

Sarcopenia, a multifactorial systemic disorder, has attracted extensive attention, yet its pathogenesis is not fully understood, partly due to limited research on the relationship between lipid metabolism abnormalities and sarcopenia. Lipidomics offers the possibility to explore this relationship. Our research utilized LC/MS-based nontargeted lipidomics to investigate the lipid profile changes as-sociated with sarcopenia, aiming to enhance understanding of its underlying mechanisms. The study included 40 sarcopenia patients and 40 control subjects matched 1:1 by sex and age. Plasma lipids were detected and quantified, with differential lipids identified through univariate and mul-tivariate statistical analyses. A weighted correlation network analysis (WGCNA) and MetaboAna-lyst were used to identify lipid modules related to the clinical traits of sarcopenia patients and to conduct pathway analysis, respectively. A total of 34 lipid subclasses and 1446 lipid molecules were detected. Orthogonal partial least squares discriminant analysis (OPLS-DA) identified 80 differen-tial lipid molecules, including 38 phospholipids. Network analysis revealed that the brown module (encompassing phosphatidylglycerol (PG) lipids) and the yellow module (containing phosphati-dylcholine (PC), phosphatidylserine (PS), and sphingomyelin (SM) lipids) were closely associated with the clinical traits such as maximum grip strength and skeletal muscle mass (SMI). Pathway analysis highlighted the potential role of the glycerophospholipid metabolic pathway in lipid me-tabolism within the context of sarcopenia. These findings suggest a correlation between sarcopenia and lipid metabolism disturbances, providing valuable insights into the disease's underlying mechanisms and indicating potential avenues for further investigation.