Lipid Homeostasis in Health and Disease

A special issue of Cells (ISSN 2073-4409).

Deadline for manuscript submissions: 20 September 2026 | Viewed by 519

Special Issue Editor


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Guest Editor
Yeast Signalling Networks Group, i3s—Instituto de Investigação e Inovação em Saúde, Universidade do Port, Porto, Portugal
Interests: lipid and energy metabolism; lipid metabolic pathways; interorganelle membrane contact sites; organelle dysfunction in disease; aging; lipid-related diseases; molecular disease mechanisms in lipid disorders
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Special Issue Information

Dear Colleagues,

Lipid homeostasis is a fundamental aspect of human physiology, ensuring the balance between lipid synthesis, storage, and degradation to maintain cellular and systemic health. Lipids serve as structural components of membranes, energy reservoirs, and signaling molecules that regulate numerous biological pathways. Disruptions in lipid homeostasis are increasingly recognized as central to the pathogenesis of many disorders, including metabolic syndrome, obesity, type 2 diabetes, cardiovascular disease, fatty liver disease, and neurodegenerative conditions. Recent advances in molecular biology, genetics, and metabolomics have shed light on the complex networks governing lipid metabolism and their integration with hormonal and nutritional signals. Moreover, the role of lipids in inflammation, oxidative stress, and immune regulation underscores their importance in health and disease. Understanding these mechanisms offers opportunities for novel diagnostics, biomarkers, and therapeutic interventions. This special focus on lipid homeostasis in health and disease aims to highlight current knowledge, emerging technologies, and translational applications that may pave the way toward personalized medicine and innovative treatments targeting lipid metabolism.

Dr. Vitor Teixeira
Guest Editor

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Keywords

  • lipids
  • metabolism
  • homeostasis
  • disease mechanisms
  • biomarkers
  • therapeutic targets
  • nutrition
  • cellular signaling
  • systems biology

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Published Papers (1 paper)

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Research

26 pages, 4714 KB  
Article
Impaired Acetyl-CoA Compartmentalization Drives a Futile Lipogenic–Oxidative Cycle in N88S Seipinopathy
by Vítor Moreira, Carlo W. T. van Roermund, Vítor Costa and Vitor Teixeira
Cells 2026, 15(5), 395; https://doi.org/10.3390/cells15050395 - 24 Feb 2026
Viewed by 256
Abstract
The N88S mutation in human seipin causes a dominant motor neuron disease marked by ER stress and inclusion body formation, lipid imbalance, and oxidative damage. However, the metabolic mechanisms connecting these defects remain poorly understood. Previous proteomic profiling in our yeast model of [...] Read more.
The N88S mutation in human seipin causes a dominant motor neuron disease marked by ER stress and inclusion body formation, lipid imbalance, and oxidative damage. However, the metabolic mechanisms connecting these defects remain poorly understood. Previous proteomic profiling in our yeast model of N88S human seipinopathy revealed decreased protein levels of enzymes involved in the tricarboxylic acid cycle, fatty acid and carboxylic acid metabolism, and the glyoxylate cycle, suggesting impaired downstream utilization of peroxisome-derived acetyl-CoA. Guided by these findings, we investigated how peroxisomal function contributes to cellular dyshomeostasis. N88S seipin-expressing cells exhibited increased peroxisome abundance but defective routing of acetyl-CoA into mitochondrial and glyoxylate pathways, resulting in elevated reactive oxygen species (ROS), impaired glyoxylate cycle activation, and reduced metabolic adaptability to non-fermentable carbon sources. Loss of peroxisomes or forced cytosolic redirection of acetyl-CoA further exacerbated ER stress, ROS accumulation, lipid peroxidation, and the growth defect on N88S seipin-expressing cells, whereas inhibition of fatty acid synthesis mitigated oxidative damage. These findings demonstrate that N88S seipin triggers a futile cycle in which misrouted cytosolic acetyl-CoA drives lipogenesis, amplifying oxidative damage and ER stress. We conclude that defective peroxisome–mitochondria metabolic coupling and acetyl-CoA misrouting may represent central pathogenic mechanisms driving cellular dysfunction in N88S-linked seipinopathy. Full article
(This article belongs to the Special Issue Lipid Homeostasis in Health and Disease)
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