Lipid droplet remodeling during salt curing-induced lipolysis in porcine muscle: Insights from lipidomics.

Cold Plasma Induced Lipid Remodeling in Meat: Identifying an Oxidative Threshold Through Integrated Lipid Oxidation and Lipidomics Analysis

The Cumulus Cell Layer Protects Bovine Maturing Oocyte Against Fatty Acid-Induced Lipotoxicity

Lipid composition-driven sorting of ABHD5 between monolayer and bilayer surfaces

Lipid droplets (LDs) are ubiquitous organelles that store neutral lipids and serve as central regulators of lipid homeostasis. Their structure includes a hydrophobic core of triacylglycerols and sterol esters surrounded by a phospholipid monolayer. This organization creates biophysical properties that guide selective protein recruitment. Among LD-associated proteins, α/β-hydrolase domain-containing protein 5 (ABHD5, also known as CGI-58) is a key regulator of lipolysis and broader lipid metabolism, yet the mechanisms guiding its distribution between endoplasmic reticulum (ER) bilayers and LD monolayers remain poorly understood. Because proper membrane association of ABHD5 is essential for activating PNPLA family lipases, identifying the determinants of its membrane selectivity is critical for understanding LD function in health and disease. In this study, we examined ABHD5 binding and sorting behavior using model membrane systems composed of giant unilamellar vesicles (GUVs) and droplet-embedded vesicles (DEVs) incorporating defined phospholipid and neutral lipid compositions. By integrating experimental assays with computational modeling, we quantified how ABHD5 partitions between bilayer membranes mimicking the ER and monolayer surfaces mimicking LDs. Systematic variation of membrane composition and physical properties allowed us to assess how packing defects and neutral lipid content shape ABHD5 localization. Our findings reveal the biophysical features that favor ABHD5 association with LD-like monolayers and provide new mechanistic insight into how cells target regulatory proteins to distinct membrane environments to control lipid metabolism.

Integrated Hepatic Lipidome Analysis in Aging Mice

Age-associated changes in lipid profiles in the liver of adult mice were consistently observed across multiple mass spectrometry platforms, and are linked to membrane structure, signaling, and metabolism, providing new insights into age-related liver dysfunction.

Cholesteryl Esters Modulate Lipid Droplet Rigidity and Monolayer Organization during Liver Cancer Progression.

In mammalian cells, lipid monolayers support the integrity of lipid droplets (LDs), organelles that function as storage sites for neutral lipids. Liver-targeting illnesses such as liver cancer interrupt normal LD metabolism and prompt changes in the chemical content of these organelles, which can have effects on the structural and organizational behavior of the lipids. In LDs, liver cancer induces concentric crystalline phases of cholesteryl esters (CEs) and triglycerides near the neutral lipid-monolayer interface, which become more pronounced as the CE concentration increases. Yet, there is little known about how this phenomenon may link to the persistence of undigested LDs in liver cancer patients. To shed light on this, all-atom molecular dynamics simulations were used to model LD micropipette aspiration experiments and gain insights into the effect of CE concentration on partitioning, structural, and mechanical properties of LDs. We successfully modeled micropipette aspiration by applying constant surface tension laterally, which stretched lipid bilayers and monolayers as the magnitude increased. The results show increased phospholipid packing due to the insertion of CE fatty tails into the monolayer. Increasing CE concentration induces a nonlinear change in surface packing defects on the LDs, notable rigidification, and stiffness. Taken together, these insights improve our understanding of the effect of CE abundance on the physical properties at the LD monolayer-core interface.

Docosahexaenoic Acid Protects Schwann Cells Against Palmitic Acid–Induced Lipotoxicity by Modulating Autophagy, ER Stress, and Lipid Handling

Elevated saturated fatty acids, such as palmitic acid (PA), induce lipotoxicity in peripheral nerve cells, a pathological feature of metabolic disorders such as type 2 diabetes and obesity that are frequently associated with neuropathic pain (NP). PA overload elicits a maladaptive stress response characterized by endoplasmic reticulum (ER) stress, disrupted intracellular calcium homeostasis, and impaired autophagic flux, ultimately promoting cell death. Although omega-3 polyunsaturated fatty acids such as docosahexaenoic acid (DHA) protect against PA-induced lipotoxicity (PA-LTx), the mechanisms linking lipid handling, ER stress, and autophagy in Schwann cells remain poorly defined. Here, we investigated how PA and DHA regulate autophagic flux, ER stress signaling, and fatty acid–binding protein 5 (FABP5)–dependent lipid trafficking in immortalized Schwann cells (ISCs). PA exposure (300 µM PA:150 µM BSA, 24–48 h) significantly reduced cell viability, impaired autophagic flux as indicated by LC3-II and p62 accumulation, disrupted autophagosome–autolysosome balance, and increased susceptibility to autophagic inhibition by chloroquine. DHA co-treatment (50 µM) preserved cell viability, restored autophagic flux, and normalized autophagosome–autolysosome fusion. Mechanistically, PA induced ER stress marked by increased CHOP, ATF4, and Xbp1 expression, along with progressive ER calcium depletion, whereas DHA suppressed these responses and stabilized calcium homeostasis. Building on prior evidence that FABP5 protects neuron-like cells from PA-LTx, we identified a regulatory role for FABP5 in Schwann cells. PA robustly induced FABP5 expression, which was normalized by DHA and modulated by pharmacological manipulation of autophagy. FABP5 silencing exacerbated PA-induced ER stress, triggered a dysfunctional compensatory autophagy response, and impaired DHA-induced lipid droplet formation. Collectively, these findings demonstrate that functional autophagy and FABP5-dependent lipid buffering are critical adaptive responses to lipotoxic stress in Schwann cells, highlighting these pathways as potential therapeutic targets for NP-associated metabolic neuropathies. Palmitic acid impairs autophagic flux and reduces Schwann cell viability, effects that are exacerbated by pharmacological inhibition of autophagy. Docosahexaenoic acid preserves Schwann cell survival during lipotoxic stress by restoring autophagic flux and autophagosome–autolysosome maturation. DHA attenuates palmitic acid–induced ER stress signaling and stabilizes intracellular calcium homeostasis in Schwann cells. FABP5 expression is regulated by lipotoxic stress and autophagy modulation, linking lipid handling to cellular stress responses. FABP5 is required for DHA-induced lipid droplet formation and supports adaptive autophagy and ER stress regulation during lipotoxic conditions.