Triclosan exposure perturbs skin lipid metabolism and inflammatory pathways: Insights from network toxicology and multi-omics analyses.

Rational engineering to enhance C8-fatty acid biosynthesis in Picosynechococcus sp. PCC 7002.

Overexpression of Hiilp2 enhances the biosynthesis of unsaturated fatty acid in Hermetia illucens.

Ammonia accumulation triggers hepatic metabolic dysregulation and oxidative damage in grass carp (Ctenopharyngodon idellus) exposed to carbonate alkalinity: A metabolomic insight.

Zearalenone induces hepatic metabolic disruption in common carp: Multi-omics evidence linking to the gut microbiota-PPARδ axis.

Multifaceted metabolic engineering of Streptomyces hygroscopicus for milbemycins overproduction.

Multi-omics integration reveals the ameliorative effects and underlying mechanisms of Astragalus membranaceus (Huangqi)-Fuzhuan brick tea on nonalcoholic fatty liver disease.

Acyl-conezyme A (CoA) synthetase family member 3 ( ACSF3 ) related combined malonic and methylmalonic aciduria (CMAMMA) is an inborn error of metabolism involving defective activation of malonic and methylmalonic acids to CoA derivatives. The resulting deficiency of malonyl-CoA disrupts mitochondrial fatty acid synthesis, lipid metabolism, and protein malonylation. Although regarded as a benign condition, studies have demonstrated that ACSF3 deficiency may lead to variable manifestations. This study aimed to expand the spectrum of ACSF3 -related CMAMMA. Four patients with biochemically and genetically confirmed ACSF3 -related CMAMMA were retrospectively analyzed for clinical, biochemical, neuroimaging, and molecular features. All patients showed elevated urinary malonic and methylmalonic acids. Two presented with mild metabolic findings such as vomiting, hypoglycemia, or growth retardation, while two exhibited neurodevelopmental phenotypes with regression, ataxia, and refractory epilepsy. One patient developed ketotic hypoglycemia during illness, and two had growth failure despite nutritional interventions. One patient carried a homozygous deletion consistent with neuronal ceroid lipofuscinosis type 7, indicating a dual diagnosis. This case series broadens the clinical spectrum of ACSF3 -related CMAMMA and reinforces that the condition extends beyond a benign biochemical abnormality. The presence of genotypes and variable neurological involvement underscores the need for comprehensive genomic testing and long-term multidisciplinary monitoring to define prognosis and guide individualized management.

Two fatty acid synthase genes (fas1 and fas2) were individually deleted in oleaginous fungus Mucor circinelloides WJ11 in our previous work. In this study, an in-depth analysis on supplement of sodium citrate and soybean oil to achieve high yields of lipid and β-carotene was investigated in fas-knockout M. circinelloides strains. The effects of different concentrations of sodium citrate or soybean oil on cell growth, lipid and β-carotene accumulation in fas-knockout strains were measured, and it was determined that the optimal addition concentrations of sodium citrate and soybean oil were both 15g/L. Combination use of 15g/L sodium citrate and 15g/L soybean oil as additives had a synergistic effect on the cell growth, lipid and β-carotene accumulation in fas-knockout strains, especially for the Mc-fas2Δ strain. The maximum yields of biomass, lipid and β-carotene in Mc-fas2Δ reached 19g/L, 33.6% and 328µg/g respectively, which were 25%, 34.4% and 2.2- fold higher than those of the control strain. Moreover, the transcriptional levels of the key genes involved in fatty acid and β-carotene synthesis in the engineered strains were significantly upregulated after adding sodium citrate and soybean oil. This is the first study to systematically evaluate the combined effects of soybean oil and sodium citrate on both lipid and β-carotene production in fas-knockout M. circinelloides strains.

Multi-omics insights into regulatory control of lipid biosynthesis during oil palm fruit maturation.

Gut microbiota and metabolites have been increasingly implicated in the pathogenesis of immune inflammation, which may be affected by environmental factors. This study aimed to explore the influence of co-exposure to high humidity and temperatures (low, normal or high) on biomarkers of immune inflammation and potential mechanisms. We established C57BL/6J mice models (with equal numbers of males and females) of high humidity and low temperature (HH-LT), normal temperature (HH-NT) or high temperature (HH-HT) co-exposure environments to observe the impact of high humidity and different temperature co-exposure environments for 28 and 56 consecutive days. Following exposure, results showed that all six combined exposure conditions significantly increased pro-inflammatory cytokines (TNF-α, IL-1β, IL-12p70), decreased anti-inflammatory cytokines (IL-4, IL-10) and elevated the Teff/Treg ratio in the spleen. Gut microbiota analysis revealed reduced Akkermansia and increased Desulfovibrio and Enterorhabdus. Serum metabolomics identified widespread disturbances enriched in pathways including protein digestion and absorption, lysine degradation, phenylalanine metabolism and unsaturated fatty acid biosynthesis. Pearson correlation analysis confirmed significant associations among microbial shifts, immune-inflammatory dysregulation and metabolic perturbations-suggesting that high humidity combined with different temperatures correlated with immune imbalance, likely mediated by gut dysbiosis and serum metabolic disruption.

Neisseria meningitidis remains a serious global health threat due to rapid progression, high mortality and rising antibiotic resistance. FabF, a key enzyme in the bacterial fatty acid synthesis (FAS II) pathway, is a promising target for new antimicrobials. A 3D model of FabF was constructed and validated and 2,583 marine natural compounds were screened for drug-likeness and ADMET properties. Molecular docking of 241 selected compounds identified three candidates with stronger binding affinity than minocycline. Compounds CMNPD5392, CMNPD14910 and CMNPD14926 showed promising interactions, indicating potential as FabF-targeted therapeutics.

Life on Earth has evolved in a form suitable for the gravitational force. Although the pivotal role of gravity in gene expression has been suggested, the molecular details remain unclear. Here, we show that mitochondria utilize gravity to activate protein synthesis within the organelle. Genome-wide ribosome profiling reveals reduced mitochondrial translation in mammalian cells and Caenorhabditis elegans under microgravity. We found that attenuation of cell adhesion through laminin-integrin interactions caused the phenotype. Mitochondrial translation is activated by a signal relayed by FAK, RAC1, PAK1, BAD, and Bcl-2 family proteins in the cytosol, and the mitochondrial fatty acid synthesis (mtFAS) pathway in the matrix. Consumption of mitochondrial malonyl-CoA by mtFAS reduces the malonylation of the translational machinery and accelerates the rates of translational initiation and elongation. Physiologically, this system operates in mechano-response of skeletal muscles. Our work provides mechanistic insights into how cells convert gravitational and mechanical forces into translation in mitochondria.

This review highlights Lunaria annua as a next‑generation industrial oilseed with a unique fatty acid profile and emerging genomic tools, positioning it for significant improvement and broad applications in biolubricants, bioplastics, and bio-based therapeutics. Lunaria annua, an ornamental of the Brassicaceae species, is emerging as a valuable oilseed crop due to its high levels of erucic and nervonic acids with applications in biolubricants, bioplastics, and neurotherapeutics. Recent advances in metabolomics, enzymology, and comparative genomics have improved understanding of fatty acid biosynthesis pathways and identified candidate genes associated with oil composition. Advances in biotechnology and breeding approaches have also provided tools for investigating traits related to oil production and environmental stress responses. However, several factors, such as agronomic performance, climatic adaptability, extraction and processing efficiency, and economic viability, require further research attention before large-scale cultivation can be considered. This review synthesizes current knowledge of L. annua biology, oil biosynthesis, and crop improvement strategies and discusses the challenges and research priorities that could influence its development as a future industrial oilseed crop.

Endocrine therapies targeting estrogen receptor alpha (ERα), expressed in ~70% of breast cancers, remain the standard of care for ER+ disease. However, 30-40% of patients experience recurrence and metastasis, with 5-year survival rates of only 31.9%. Using the Carle Foundation Hospital cohort and liver metastatic patient-derived xenograft models, we identified upregulated lipid metabolism and acetyl-CoA production as metabolic vulnerabilities. We demonstrate that combining Fulvestrant (Fulv) with an inhibitor of Acyl-CoA Synthetase Short Chain Family Member 2 (ACSS2) synergistically reduces metastatic breast cancer cell viability. Through isotope tracing, CUT&RUN sequencing, immunofluorescence, western blot, and RNA sequencing, we show that Fulv increases ACSS2 expression and acetate utilization, redirecting acetate flux from the TCA cycle toward fatty acid synthesis. Nuclear ACSS2 chromatin occupancy increases with Fulv treatment, expanding ERα/ACSS2/H3K27ac co-occupancy at tumor progression genes, an effect abolished by ACSS2 inhibition. RNA sequencing revealed that ACSS2 inhibition suppresses Fulv-induced metabolic and oncogenic transcriptional programs. In a therapy-resistant xenograft model, combination treatment reduced Fulv-dependent metastatic burden. These findings establish ACSS2 as a driver of endocrine resistance through nuclear acetyl-CoA provision for epigenetic reprogramming, representing a novel therapeutic target in metastatic breast cancer.

Perfluoroalkyl substances (PFAS) are organic compounds with widespread environmental occurrence and documented associations with multiple health effects. The pathophysiology remains unclear, although there are indications of potential involvement of metabolic pathways. To evaluate associations between serum PFAS concentrations and the metabolome in Swedish adults. We conducted an extensive metabolome-wide association analysis (MWAS) to explore the potential links between serum metabolites and serum concentrations of PFOS, PFOA, and PFHxS in a cohort comprising 2353 participants from the EpiHealth study. Liquid chromatography coupled with mass spectrometry was used to obtain levels of PFAS and 790 distinct non-xenobiotic metabolites. Results were validated in 1104 participants from the POEM and PIVUS cohort. Linear regression models were adjusted for age, sex, BMI, smoking, exercise, education, and diabetes. 236 metabolites were validated to be significantly associated with PFOS, and 190 metabolites associated with PFOA using FDR < 0.05. No significant associations could be validated for PFHxS. The metabolites showing the strongest associations with both PFOS and PFOA were various lipid-related metabolites, including long-chain polyunsaturated fatty acids (n3 and n6), saturated fatty acids, and monounsaturated fatty acids. Also, lysophospholipids, sphingomyelins, phosphatidylcholines, as well as various amino acids, were related to the two PFAS. Metabolic pathway analysis identified significant enrichment of metabolites involved in branched-chain amino acid biosynthesis, synthesis of unsaturated fatty acids, and arginine biosynthesis. This study provides a large-scale, externally validated map of metabolites associated with background human exposure to major PFAS. In a population-based metabolome-wide association study (MWAS) with independent validation, PFOS and PFOA showed robust associations with lipid classes and amino acids, whereas no associations were validated for PFHxS. These findings strengthen biological plausibility for PFAS-health associations and prioritize metabolic pathways for future mechanistic and environmental epidemiology studies.

Intramuscular fat (IMF) and unsaturated fatty acid (UFA) contents are critical factors influencing meat quality in livestock. Circular RNAs (circRNAs) have recently emerged as key regulators in lipid metabolism. However, their roles in IMF deposition and UFA synthesis remain largely unexplored in buffalo. Here, high-throughput sequencing of six adipose depots combined with WGCNA identified a novel circRNA (circFAM129B) that was highly correlated with UFA content in buffaloes. The authenticity of circFAM129B was confirmed by sequencing and RNase R treatment. Overexpression of circFAM129B upregulated the expression of adipogenesis and UFA synthesis genes, enhancing lipid accumulation and UFA content, while inhibiting cell proliferation. Mechanistically, circFAM129B sponges bta-let-7d, alleviating its inhibitory effect on SCD. These findings unveil a novel circRNA-mediated regulatory axis modulating adipogenesis and UFA synthesis, offering potential molecular targets for enhancing meat quality and nutritional value in buffaloes.

Intestinal-specific ketohexokinase deficiency ameliorates high fructose-induced metabolic dysfunction across the intestinal-liver-kidney axis in mice.

Pyrazinamide-derived 1,2,3-triazoles: Antimicrobial evaluation, selective antimycobacterial activity and mechanism of action insights.

Silent corticotroph adenomas (SCAs) are an aggressive pituitary neuroendocrine tumor (PitNET) subtype lacking effective medical therapies and showing a high rate of recurrence. The molecular mechanisms driving their proliferation remain poorly understood. Although metabolic reprogramming is a hallmark of cancer, neither lipid metabolism nor its regulatory pathways have been systematically investigated in SCAs. We performed integrative analyses of bulk and single-cell RNA sequencing datasets from SCAs, functioning corticotroph adenomas (FCAs), and normal pituitary tissue to characterize GAL expression and associated signaling pathways. Mechanistic studies employed GAL gain- and loss-of-function models, RNA sequencing, luciferase reporter assays, lipidomics, and pharmacological inhibition. Regulation of GAL by MYCN was assessed through promoter transactivation assays. The therapeutic efficacy of SREBP1 inhibition (fatostatin) was evaluated both in vitro and in vivo. We identified a marked downregulation of galanin (GAL) in SCAs and demonstrated that GAL loss promotes tumor cell proliferation. GAL deficiency activated the PI3K-Akt-mTOR signaling cascade, resulting in increased activity of SREBP1, a key transcriptional regulator of lipogenesis. Enhanced fatty-acid synthesis provided metabolic support for SCA growth. We further uncovered a linear regulatory axis in which MYCN directly upregulates GAL; however, MYCN downregulation in SCAs suppresses GAL expression, thereby enabling SREBP1-driven lipogenesis. Pharmacological inhibition of SREBP1 with fatostatin reduced lipogenesis and significantly suppressed SCA growth in vitro and in vivo. Our findings reveal a previously unrecognized MYCN-GAL-SREBP1 lipogenic axis that drives SCA proliferation. SREBP1-dependent lipogenesis represents a promising and druggable therapeutic vulnerability for the treatment of SCAs.