Background: Diet-induced disordered phospholipid metabolism and disturbed macrophage metabolism contribute to the pathogenesis of metabolic diseases. However, the effects of oleate, a main dietary fatty acid, on macrophage phospholipid metabolism are unclear.
Objectives: We aimed to discover oleate-induced disorders of macrophage phospholipid metabolism and potential therapeutic targets for treating diet-related metabolic diseases.
Methods: RAW 264.7 cells were exposed to 65 μg oleate/mL, within the blood concentration range of humans and mice, to trigger disorders of phospholipid metabolism. Meanwhile, WY-14643 and pioglitazone, 2 drugs widely used for treating metabolic diseases, were employed to prevent oleate-induced disorders of macrophage phospholipid metabolism. Subsequently, an untargeted metabolomics approach based on liquid chromatography-mass spectrometry was used to discover relevant metabolic disorders and potential therapeutic targets.
Results: We showed that 196 metabolites involved in phospholipid metabolism were altered upon oleate treatment and interventions of WY-14643 and pioglitazone (P < 0.05, 2-tailed Mann-Whitney U test). Notably, most lysophospholipids were decreased, whereas most phospholipids were increased in oleate-treated macrophages. Phosphatidylethanolamines accumulated most among phospholipids, and their acyl chain polyunsaturation increased in oleate-treated macrophages. Additionally, saturated fatty acids were decreased, whereas polyunsaturated fatty acids were increased in oleate-treated macrophages. Furthermore, changes in phosphatidylglycerols, phosphatidylinositols, cardiolipins, phosphatidates, lysophosphatidylglycerols, and acylcarnitines in oleate-treated macrophages could be attenuated or even abolished by WY-14643 and/or pioglitazone treatment.
Conclusions: Oleate induced accumulation of various phospholipids, increased acyl chain polyunsaturation of phosphatidylethanolamines, and decreased lysophospholipids in RAW 264.7 macrophages. This study suggests macrophage phospholipid and fatty acid metabolism as potential therapeutic targets for intervening diet-related metabolic diseases.
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http://dx.doi.org/10.1093/jn/nxaa411 | DOI Listing |
PLoS One
January 2025
Hebei General Hospital, Shijiazhuang City, Hebei Province, P.R. China.
Objective: To study the effect of Dapagliflozin on ferroptosis in rabbits with chronic heart failure and to reveal its possible mechanism.
Methods: Nine healthy adult male New Zealand white rabbits were randomly divided into Sham group (only thorax opening was performed in Sham group, no ascending aorta circumferential ligation was performed), Heart failure group (HF group, ascending aorta circumferential ligation was performed in HF group to establish the animal model of heart failure), and Dapagliflozin group (DAPA group, after the rabbit chronic heart failure model was successfully made in DAPA group). Dapagliflozin was given by force-feeding method.
Redox Rep
December 2025
Department of Hematology, Shenzhen Qianhai Shekou Pilot Free Trade Zone Hospital, Shenzhen, People's Republic of China.
Background: Regenerative medicine researches have shown that mesenchymal stem cells (MSCs) may be an effective treatment method for premature ovarian insufficiency (POI). However, the efficacy of MSCs is still limited.
Purpose: This study aims to explain whether salidroside and MSCs combination is a therapeutic strategy to POI and to explore salidroside-enhanced MSCs inhibiting ferroptosis via Keap1/Nrf2/GPX4 signaling.
J Chem Phys
January 2025
School of Chemistry, University of Southampton, Highfield, Southampton SO17 1BJ, United Kingdom.
Membrane properties are determined in part by lipid composition, and cholesterol plays a large role in determining these properties. Cellular membranes show a diverse range of cholesterol compositions, the effects of which include alterations to cellular biomechanics, lipid raft formation, membrane fusion, signaling pathways, metabolism, pharmaceutical therapeutic efficacy, and disease onset. In addition, cholesterol plays an important role in non-cellular membranes, with its concentration in the skin lipid matrix being implicated in several skin diseases.
View Article and Find Full Text PDFLife Metab
December 2024
Key Laboratory of Phytochemistry and Natural Medicines, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, Liaoning 116023, China.
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a metabolic disease that can progress to metabolic dysfunction-associated steatohepatitis (MASH), cirrhosis, and cancer. The zonal distribution of biomolecules in the liver is implicated in mediating the disease progression. Recently, G-protein-coupled receptor 35 (GPR35) has been highlighted to play a role in MASLD, but the precise mechanism is not fully understood, particularly, in a liver-zonal manner.
View Article and Find Full Text PDFMol Plant
January 2025
State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, School of Agriculture, Yunnan University, Kunming 650540, China; Southwest United Graduate School,Kunming 650500, China. Electronic address:
Potato is the world's most important nongrain crop. Here, we report that 29 genomes from Petota and Etuberosum sections were de novo assembled, and that 248 accessions of wild potatoes, landraces and modern cultivars were re-sequenced at > 25× depth to assess genetic diversity within the Petota section. Subsequently, a graph-based pangenome was constructed by using DM8.
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