Effects of obacunone against myocardial fibrosis: Mechanistic insights from network pharmacology and experimental validation.

Membrane contact sites, where organelle membranes come into close proximity, function as dynamic hubs for lipid metabolism in response to metabolic and stress signals. In yeast, the nucleus-vacuole junction (NVJ) expands during glucose starvation (GS) through the recruitment of stress-specific proteins; however, the underlying mechanisms and physiological significance have remained unclear. Here, we identify the aspartyl protease Ypf1 and the yeast INSIG homologs Nsg1 and Nsg2 as NVJ-localized proteins specifically recruited during GS. Ypf1 promotes the recruitment of Nsg1, Nsg2, and the HMG-CoA reductases Hmg1 and Hmg2 to the NVJ, likely in association with changes in nuclear membrane lipid composition caused by suppression of fatty acid elongases. This remodeling destabilizes Nsg1, thereby activating Hmg1, while stabilizing Nsg2, which suppresses Hmg1 to fine-tune sterol synthesis. Loss of both Nsg1 and Nsg2 leads to hyperactivation of Hmg1 and accumulation of squalene, a sterol biosynthetic intermediate. We propose that suppression of fatty acid elongases drives GS-dependent NVJ remodeling to regulate ergosterol synthesis.

Seipin is a conformationally flexible, oligomeric scaffold that regulates cellular lipid homeostasis beyond lipid droplet (LD) biogenesis. Seipin senses local lipid composition and membrane features to direct metabolic flux toward specific pathways and organelles. Its ring adopts multiple conformations, influenced by cofactors such as the LD assembly factor 1 and adipogenin, as well as lipid ligands including phosphatidic acid, diacylglycerol, and triacylglycerol, conferring broad functional versatility. Although seipin is an ER-resident protein primarily enriched at ER-LD junctions, a fraction relocates to mitochondria-associated membranes under specific metabolic conditions, where it regulates lipid synthesis, turnover, and local Ca2+ levels, thereby facilitating interorganelle communication and maintaining metabolic stability. Seipin dysfunction disrupts this multinodal regulation, causing lipid imbalance, organelle abnormalities, and a range of metabolic and neuronal disorders. We propose a unified model in which seipin functions as a multistate proteolipid regulatory hub: a rheostat whose structure and interactome dynamically adjust to control lipid pathway decisions in response to metabolic signals across organelle contact networks.

Camel milk-derived Lentilactobacillus parabuchneri L-185 produces acid-associated metabolites that inhibit MRSA growth and biofilm formation in milk.

From economic crop to high-value product: Fermentation of chestnut protein by Lactobacillus rhamnosus ameliorates chronic inflammation via the gut microbiota-SCFAs axis.

Perinatal exposure to nonylphenol reprograms hepatic clock machinery and energy metabolism in rat offspring.

Zhujing Pill ameliorates age-related macular degeneration by regulating lipid metabolism, complement activation, and inflammatory responses: an integrated network pharmacology and metabolomics study.

Endothelial dysfunction is a risk factor for lipid metabolism disorders: underlying mechanisms and potential treatments.

Dual biomarkers ALOX5AP and INPP4A are associated with lipid metabolism and neutrophil extracellular traps in periodontitis: A bioinformatics and clinical validation study.

Bisphenol A exposure disrupts the circadian clock system and impairs glycolipid metabolic function in mice liver.

Prolonged exposure to aflatoxin B1 (AFB1) poses a significant threat to livestock production. The liver is the main target, but the role of the gut-liver axis and lipid metabolism in pig hepatic toxicity is not well understood. This study evaluates the impact of AFB1 on piglet liver injury via the gut-liver axis using multiomics analysis. Chronic AFB1 exposure significantly impaired the piglet growth and induced liver injury. Meanwhile, AFB1 caused gut microbiota dysbiosis and intestinal barrier damage in the piglets. Fecal microbiota transplantation (FMT) demonstrated that AFB1-altered microbiota causally contribute to hepatic inflammation in mice. Multiomics analysis revealed systemic disruption of lipid metabolism pathways, which might be involved in the intestinal flora imbalance caused by AFB1. Abnormal lipid metabolism subsequently leads to the accumulation of inflammatory lipid mediators in the plasma, ultimately causing severe liver damage. The findings highlight the crucial roles of gut microbiota and lipid metabolism in AFB1-induced liver toxicity.

Acute myeloid leukemia (AML) remains difficult to cure, in part related to strong genetic and functional heterogeneity between and within individual patients. Metabolic reprogramming is emerging as an important feature of AML cells, allowing exploration of alternative treatment strategies. Here, we describe a novel DHODH inhibitor, JNJ-74856665, that showed strong efficacy in a subset of AML samples. In a multi-omics approach, by combining label-free quantitative proteome data with drug sensitivity data in bone marrow stromal co-cultures in a large cohort of primary AML patient samples we identified that sensitivity to DHODH inhibition (DHODHi) is linked to cholesterol and lipid metabolism. DHODHi resulted in an accumulation of cholesterol, mitochondrial reactive oxygen species (ROS) and lipid peroxidation. LC-MS/ MS-based lipidomics studies revealed that DHODHi resulted in a strong increase in polyunsaturated fatty acids and triglycerides, which are the primary lipid species stored in lipid droplets (LD). We hypothesized that this might be the consequence of increased ROS and lipid peroxidation levels, prompting the cell to detoxify such toxic lipid species by storing them in LD. Indeed, we could observe a marked increase in LD formation upon DHODHi. The transcriptional regulator SREBF2, known to control cholesterol and lipid metabolism, was up-regulated in DHODHi sensitive AML, and a strong synergy was observed between the combination of both DHODHi and the SREBP inhibitor dipyridamole. Our data indicate that it would be interesting to further explore combined DHODH and SREBP inhibition as a therapeutic target option in AML.

Epithelial ovarian cancer (EOC) is a highly aggressive malignancy with poor prognosis. Thus, new treatment options are needed. Recently, lipid metabolism in EOC has been highlighted. However, the specific lipid molecules activating lipid metabolism remain unclear. This study aimed to elucidate lipid metabolism in EOC and evaluate the potential of its inhibition as a therapeutic approach. We obtained high-fat diet (HFD)-fed mouse serum and performed metabolome analysis to identify lipid molecules contributing to cell proliferation of EOC. We also analyzed which signaling pathway was activated by the lipid molecule. Finally, we demonstrated the inhibition of lipid metabolism in EOC cells. HFD significantly promoted tumor growth of EOC cells in vivo, and HFD-fed mouse serum promoted EOC cell proliferation in vitro. Metabolome analysis identified cholesterol (C27H46O) as a key molecule in HFD-fed mouse serum. Cholesterol (C27H46O) activated the Akt/mTOR signaling pathway in vitro. Cholesterol (C27H46O) is an important component of lipid rafts, and its inhibitor, which extracts cholesterol (C27H46O) from lipid rafts, inactivated the Akt/mTOR signaling pathway and suppressed subsequent EOC cell proliferation. Exogenous cholesterol (C27H46O) contributed to cell proliferation of EOC via the lipid rafts-Akt/mTOR signaling pathway, and its inhibition undoubtedly presents a novel therapeutic strategy for EOC.

Caveolin-1 deficiency exacerbates liver fibrosis by driving lipid metabolic reprogramming in hepatic stellate cells via DRP1-mediated mitochondrial fission.

Withering-induced lipid metabolism remodeling underpins the formation of tea aroma.

Non-alcoholic fatty liver disease (NAFLD) is a common metabolic disorder characterized by excessive lipid accumulation in hepatocytes and is strongly associated with obesity, insulin resistance, and dyslipidaemia. Targeting key regulators of hepatic lipid metabolism represents an important therapeutic strategy. Vinpocetine, a phosphodiesterase-1 inhibitor, exhibits metabolic and anti-inflammatory properties, but its role in hepatic lipid homeostasis remains insufficiently defined. To evaluate the effect of vinpocetine on hepatic steatosis and its regulatory impact on key lipid-metabolism genes, including peroxisome proliferator-activated receptor-α (PPAR-α), PPAR-γ, sterol regulatory element-binding protein-1c (SREBP-1c), and fatty acid translocase/cluster of differentiation 36 (FAT/CD36), in an experimental NAFLD model. NAFLD was induced in rats using a high-fat diet. Animals received vinpocetine (10 mg/kg, i.p.) daily for 5 weeks. Hepatic lipid accumulation was assessed histologically and biochemically, while gene expression of PPAR-α, PPAR-γ, SREBP-1c, and FAT/CD36 was analyzed using RT-PCR. Vinpocetine significantly reduced hepatic lipid accumulation compared with untreated NAFLD controls. It upregulated PPAR-α expression while downregulating PPAR-γ, SREBP-1c, and FAT/CD36, indicating enhanced fatty-acid oxidation and reduced lipogenesis and lipid influx. Treatment also improved lipid profile parameters (reduced TC, TG, LDL, and restored HDL), lowered liver enzyme levels, increased antioxidant activity (elevated glutathione), and reduced oxidative and nitrosative stress (decreased malondialdehyde and nitric oxide), accompanied by improved liver histology. Vinpocetine attenuates hepatic steatosis in NAFLD by modulating genes involved in lipid metabolism, suggesting potential therapeutic value. Further studies are required to confirm these findings and clarify mechanisms.

Microglia, lipids, and their interaction are found to play important roles in post-stroke immunity. Microglia are sensitive to detect environment change in injured brain. Activated microglia undergo phenotypical remodeling and trigger complex signal cascades to regulate immune responses after stroke. Lipids including peripheral lipid metabolism and lipid droplet biogenesis are involved in the control of microglia functions, such as activation, phagocytosis, proliferation, and pro-inflammation. In this review, we explore new scope of microglia and lipids in immune regulation of stroke. Implication of peripheral lipid metabolism after stroke is mentioned and advances in microglia-lipid interaction are discussed. We give a special focus on how diet and gut microbiome influence neuroinflammation system via gut-brain axis, and how these processes associate with the risk and outcome of stroke. Moreover, we reviewed the therapeutic targets related to lipid metabolism and microglial modulation after stroke. These can provide a prospective strategy for more efficient and safer treatment for ischemic and hemorrhagic stroke.

Dietary supplementation of Radix Isatidis polysaccharides improves meat quality in broilers by regulating lipid metabolism, antioxidant defense, and the gut-muscle axis.

10-epi-PDX alleviates high-fat-diet-induced obesity by modulating lipid droplet dynamics and restoring metabolic balance.

Hereditary PCOS and the environmental toxicant F-53B converge on lipid metabolic reprogramming to impair fetal brain development.