Bioactive Lipids in Disease: Diagnosis, Prognosis, and Pathophysiology

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Molecular and Translational Medicine".

Deadline for manuscript submissions: 31 July 2026 | Viewed by 1263

Special Issue Editor

School of Basic Medical Sciences, Peking University, Beijing, China
Interests: bioactive lipids metabolism; pathophysiology of cardiovascular diseases; biomarker discovery; metabolomics methodology

Special Issue Information

Dear Colleagues,

The paradigm of lipid biology has evolved dramatically, shifting the scholarly view of lipids from simple structural components or energy depots to critical regulators of cellular and systemic physiology. Among them, bioactive lipids represent an exceptionally diverse and potent class of signaling molecules that regulate a vast array of biological processes. A deeper understanding of these lipids is fundamental to unraveling the mechanisms underlying numerous human diseases, including metabolic disorders, cardiovascular diseases, cancer, and neurodegenerative conditions.

A key feature of bioactive lipids is their ability to enter systemic circulation, making them highly valuable as accessible biomarkers. Their dynamic levels in blood and other biofluids can reflect underlying pathological states, offering powerful tools for early diagnosis, patient stratification, prognostic assessment, and therapeutic response monitoring.

Despite substantial progress in lipidomics research, a significant proportion of bioactive lipids remains uncharacterized. The integration of advanced analytical methodologies presents opportunities for the discovery and functional characterization of novel bioactive lipid entities.

This Special Issue welcomes research contributions that enhance our understanding of bioactive lipids in disease, including studies on disease mechanisms, biomarker identification, therapeutic applications, and new methodological developments in lipid research. We encourage submissions of both original research articles and comprehensive review articles that bridge scientific discoveries with clinical applications.

Dr. Xu Zhang
Guest Editor

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Keywords

  • bioactive lipids
  • eicosanoids
  • endocannabinoids
  • lysophospholipids
  • sphingolipids
  • oxysterols
  • bile acids
  • lipidomics
  • pathophysiology
  • biomarkers

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Published Papers (1 paper)

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Research

20 pages, 2291 KB  
Article
Opposite Effects of Diacylglycerol and Phosphatidic Acid in the Modulation of the Plasma Membrane Ca2+-ATPase from Kidney Proximal Tubules: A Regulatory Role for Diacylglycerol Kinase in Calcium Homeostasis?
by Gloria M. R. S. Grelle, Pilar A. M. Moreno, Thais A. Bonilha, Osman F. Silva, Rafael Garrett, Fábio Ricardo M. Botelho, Luciana Nogaroli, Rafael H. F. Valverde and Marcelo Einicker-Lamas
Biomedicines 2026, 14(2), 388; https://doi.org/10.3390/biomedicines14020388 - 8 Feb 2026
Viewed by 906
Abstract
Background/Objectives: Kidney proximal tubules reabsorb up to 70% of water and solutes from the glomerular ultrafiltrate, a Ca2+-modulated process essential for homeostasis. The plasma membrane Ca2+-ATPase (PMCA) in basolateral membranes (BLMs) plays a pivotal role in maintaining intracellular [...] Read more.
Background/Objectives: Kidney proximal tubules reabsorb up to 70% of water and solutes from the glomerular ultrafiltrate, a Ca2+-modulated process essential for homeostasis. The plasma membrane Ca2+-ATPase (PMCA) in basolateral membranes (BLMs) plays a pivotal role in maintaining intracellular calcium homeostasis and regulating calcium reabsorption. Methods: Here, we investigated the regulatory influence of two key bioactive lipids, diacylglycerol (DG) and phosphatidic acid (PA), on PMCA activity from pig kidney, accompanied by lipidomic assays and transcriptomic data analyses. Results: Biochemical assays revealed dose- and time-dependent inhibition of PMCA by DG, fully reversed by Calphostin C, implicating PKC activation. Conversely, PA significantly stimulated PMCA activity, demonstrating an opposite regulatory effect. Our targeted lipidomics identified multiple DG species in HK-2 cells, suggesting substrate diversity. Analysis of transcriptomic data for hypoxic versus normoxic HK-2 cells revealed dramatic coordinated regulation of DG/PA metabolism genes, with upregulation of DG-producing enzymes (PLCB1, PLDs) and downregulation of DG-consuming kinases (DGKs), predicting enhanced DG accumulation under metabolic stress. ATP2B4 (PMCA4) upregulation indicated compensatory transcriptional responses. Conclusions: Our findings suggest that DG inhibits BLM-associated PMCA via classic and/or atypical PKC-dependent phosphorylation while PA exerts opposing stimulatory effects. Both transcriptional remodeling and post-translational modifications regulate this axis. These findings highlight the DG–Diacylglycerol Kinase–PA axis as a dynamic modulator of Ca2+ signaling in the kidney that responds to metabolic stress. Full article
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