Novel eicosanoid signature in plasma provides diagnostic for metabolic dysfunction-associated steatotic liver disease.

There is a clinical need for a simple test implementable at the primary point of care to identify individuals with metabolic dysfunction-associated steatotic liver disease (MASLD) in the population. Blood plasma samples from adult patients with varying phenotypes of MASLD were used to identify a minimal set of lipid analytes reflective of underlying histologically confirmed MASLD. Samples were obtained from the NIDDK Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) NAFLD Database prospective cohort study (MASLD group; N = 301).

Homeocurvature adaptation of phospholipids to pressure in deep-sea invertebrates.

Hydrostatic pressure increases with depth in the ocean, but little is known about the molecular bases of biological pressure tolerance. We describe a mode of pressure adaptation in comb jellies (ctenophores) that also constrains these animals' depth range. Structural analysis of deep-sea ctenophore lipids shows that they form a nonbilayer phase at pressures under which the phase is not typically stable.

Lipidomics of phospholipase A reveals exquisite specificity in macrophages.

Phospholipase A (PLA) constitutes a superfamily of enzymes that hydrolyze phospholipids at their sn-2 fatty acyl position. Our laboratory has demonstrated that PLA enzymes regulate membrane remodeling and cell signaling by their specificity toward their phospholipid substrates at the molecular level. Recent in vitro studies show that each type of PLA, including Group IVA cytosolic PLA (cPLA), Group V secreted PLA (sPLA), Group VIA calcium independent PLA (iPLA) and Group VIIA lipoprotein-associated PLA, also known as platelet-activating factor acetyl hydrolase, can discriminate exquisitely between fatty acids at the sn-2 position.

Cholesterol-dependent LXR transcription factor activity represses pronociceptive effects of estrogen in sensory neurons and pain induced by myelin basic protein fragments.

Background: A bioactive myelin basic protein (MBP) fragment, comprising MBP, is released in sciatic nerve after chronic constriction injury (CCI). Intraneural injection (IN) of MBP in an intact sciatic nerve is sufficient to induce persistent neuropathic pain-like behavior via robust transcriptional remodeling at the injection site and ipsilateral dorsal root ganglia (DRG) and spinal cord. The sex (female)-specific pronociceptive activity of MBP associates with sex-specific changes in cholesterol metabolism and activation of estrogen receptor (ESR)1 signaling.

Synovial 5-Lipoxygenase-Derived Oxylipins Define a Lympho-Myeloid-Enriched Synovium.

Objective: Oxylipins are bioactive lipids derived from polyunsaturated fatty acids (PUFAs) that modulate inflammation and may remain overexpressed in refractory synovitis. In plasma, they could also be biomarkers of synovial pathology. The aim of this study is to determine if synovial oxylipins in inflamed joints correlate with plasma oxylipins and with synovial histologic patterns.