Biology subjects

Guttula, P.

Publications and source records attributed to Guttula, P..

4 recordsLinked to original sources

bioRxiv2026

Comparative Metabolomic Profiling Reveals Salinity Tolerance Mechanisms in a Rice Introgression Line

Rice (Oryza sativa) is highly sensitive to salinity, yet the metabolic mechanisms underlying salt tolerance remains incompletely understood. In this study, we performed leaf tissue-specific untargeted metabolomic profiling of the salt-tolerant introgression line JN100 (JN), its donor parent Nona Bokra (NB), and its recurrent parent Jupiter (JU) to characterize metabolic responses to salt stress. Comparative analysis identified differentially accumulated metabolites (DAMs) spanning diverse chemical classes, including amino acids, sugars and carbohydrates, lipids, organic acids, cofactors, electron carriers, and nucleotides. Under salt stress (SS), 201 DAMs (89 upregulated and 112 downregulated) were detected in JN relative to JU. Notably, metabolites such as allantoin, glycitin, nicotinamide ribotide, D-arabinono-1,4-lactone, violanthin, L-methionine S-oxide, ribitol, lysine, rutin, glutamine, pantothenic acid, and quinic acid, showed significant differential accumulation. Pathway enrichment analysis revealed significant enrichment of arginine biosynthesis, purine metabolism, and alanine, aspartate, and glutamate metabolism, indicating extensive reprogramming of nitrogen and energy-associated metabolic pathways under salinity stress. Integration of transcriptomic and metabolomic datasets from the SS experiments further identified ten differentially expressed genes (DEGs) associated with the metabolite network in the JN vs. JU comparison. Among these, OsDHQDT/SDH, OsFd-GOGAT, phenylalanyl-tRNA synthetase, OsP5CS1, OsP5CS2, and a pyridoxal phosphate-dependent transferase were linked to metabolites involved in shikimate, amino acid, and proline metabolism. Collectively, these results demonstrate that salinity tolerance in rice is associated with coordinated transcriptional and metabolic reprogramming that supports oxidative stress mitigation and adaptive stress responses.

plant biology↗

bioRxiv2026

Integrated Lipidomics and Nitro-Fatty Acid Profiling Link Adipose Redox Imbalance to Alzheimer's Disease-Related Neurovascular Injury

Alzheimers disease (AD) is increasingly recognized as a systemic disorder in which peripheral metabolic and redox dysfunction affects neurovascular injury and amyloid pathology. However, the lipid-redox mechanisms linking adipose tissue dysfunction to AD are less explored. Here, we applied an integrated multi-omics and imaging approach to investigate adipose lipid remodelling that leads to nitric oxide (NO)-derived nitro-fatty acid modifications and their effects on {beta}-amyloid and VEGF in the hippocampus of APP/PS1 mice. Targeted lipidomics revealed broad suppression of lysophospholipids and membrane phospholipids (LPC, PC, PE, PG) in gonadal white adipose tissue (gWAT), consistent with impaired membrane turnover and mitochondrial lipid deficiency. Untargeted lipidomics demonstrated accumulation of ceramides, triacylglycerols, monoacylglycerols, and phosphatidic acids, indicating lipotoxicity and disrupted lipid flux. Oxidized lipid mediator profiling showed increased 13-HODE, 12-HETE, and 14-HDHA. Further, Raman microscopy mapping revealed a shift from protective nitro-oleic acid toward increased nitration of polyunsaturated fatty acids. These lipid abnormalities coincided with increased adipose expression of redox and inflammatory markers, including NOX4 and TNF-, and impaired mitochondrial redox metabolism assessed by fluorescence lifetime imaging (FLIM). Citrulline and nitrite treatments partially normalized adipose lipid-redox signatures. Citrulline restored phospholipid remodeling and nitro-oleic acid signaling, whereas nitrite preferentially enhanced stress-associated signaling lipids. Importantly, both interventions reduced hippocampal {beta}-amyloid burden and restored VEGF expression, with citrulline producing the strongest neurovascular rescue. These findings identify adipose lipid-redox imbalance as a systemic contributor to neurovascular pathology in AD and highlight NO-directed metabolic modulation as a strategy to mitigate disease-associated lipid dysfunction.

molecular biology↗

bioRxiv2026

Phosphoglycerate mutase 5 regulates lipid metabolism and mitochondrial homeostasis in hepatocellular cancer cells

The mitochondrial membrane protein phosphoglycerate mutase 5 (PGAM5) is a protein of interest in the complex transition from hepatic steatosis to hepatocellular carcinoma. PGAM5 is a serine/threonine/histidine phosphatase that plays a role in mitochondrial biogenesis, mitophagy, and multiple cell death pathways. Increased expression of PGAM5 in hepatocellular carcinoma is correlated with reduced patient survival. In this study, we demonstrate that loss of PGAM5 alters the bioenergetic landscape of liver cancer by promoting mitochondrial oxidant injury and suppressing the glycerophospholipid and lysophospholipid pathways, leading to accumulation of the bioactive phospholipid lysophosphatidylcholine. Additionally, PGAM5 deletion downregulates fatty acid biosynthesis, resulting in reduced cellular diacylglycerol concentrations through two probable mechanisms: attenuated long chain fatty acid uptake and suppressed de novo synthesis. These findings underscore the broad impact of a single phosphatase on mitochondrial function and provide a rationale for therapeutically targeting PGAM5 to disrupt lipid metabolism in hepatocellular carcinoma.

cancer biology↗

bioRxiv2025

Multiomics Integration Reveals a Metabolic Myopathy in Cardiometabolic HFpEF

BackgroundSkeletal muscle dysfunction is a major peripheral determinant of exercise intolerance and physical disability in heart failure with preserved ejection fraction (HFpEF). Metabolic and mitochondrial dysfunction are considered to be key components of skeletal muscle dysfunction, but comprehensive profiling of metabolic pathways has not been conducted. Elucidation of dysregulated metabolic pathways is essential to determine viable targets for the treatment of exercise intolerance in HFpEF. MethodsMale ZSF1 Obese rats (HFpEF) and Wistar Kyoto (WKY) lean normotensive controls were studied at 26 weeks of age. Gastrocnemius was subjected to bulk RNA-seq, proteomics, metabolomics, and lipidomics analysis. The R package limma was used to determine differential expression in all omics layers (absolute fold-change>1.5, FDR0.05, unless otherwise indicated). Additional targeted plasma and skeletal muscle (soleus and EDL) metabolomics and lipidomics were performed on HFpEF and control rats. ResultsPathway level analysis for RNA seq and proteomics revealed significant downregulation of oxidative phosphorylation (NES -2.1, p<0.005), electron transport chain (NES -2.0, p<0.005), and TCA cycle (-1.8, p<0.05). The most upregulated pathways were PPAR signaling (NES 2.2, p<0.0001), tryptophan metabolism (NES 1.8, P<0.005), and amino acid oxidation (NES 1.8, p<0.005) pathways. Metabolomics revealed an accumulation of TCA cycle intermediate, isocitrate, and phosphate reduction. Branched-chain amino acids were significantly increased, whereas amino acids related to tryptophan metabolism were reduced and shifted towards increased serotonin accumulation. Phospholipid species were differentially regulated with increased palmitoylated phosphatidylcholines but reduced arachidonoyl-PC species. Phosphatidylethanolamines (PE) species (16:0/16:1-18:0/18:2) were increased. ConclusionOur multiomics analysis of skeletal muscle in HFpEF revealed severe mitochondrial dysfunction that was characterized by reduced complex I and II activity. Mitochondrial and peroxisomal lipid overload results in a shift in membrane phospholipid accumulation and composition. Reduced BCAA oxidation and dysregulation of tryptophan metabolism are key features of amino acid metabolism that reduce anaplerosis and promote the accumulation of toxic metabolites. Comparative analysis of other skeletal muscle disorders suggests that an acquired metabolic myopathy exists in cardiometabolic HFpEF.

physiology↗