Ornithine (OR) is a key intermediate metabolite; however, its molecular role in obesity remains unclear. This study aimed to investigate the effects of OR and its rate-limiting enzyme, ornithine decarboxylase 1 (ODC1), on lipid metabolism using high-fat diet (HFD)-induced obese C57BL/6 mice and C3H10T1/2 cell models. The results showed that OR supplementation and ODC1 overexpression exerted similar effects, including significantly aggravated HFD-induced obesity, elevated serum polyamine levels, impaired glucose tolerance, reduced oxygen consumption, and hepatic steatosis. Transcriptomic analysis combined with protein validation indicated that ODC1-promoted lipid deposition is associated with suppression of the AMPK/ACC pathway. Invitro, ODC1 overexpression promoted adipocyte proliferation and differentiation, accompanied by elevated levels of polyamines, including putrescine, spermidine, and spermine. Increased polyamine turnover further induced polyamine catabolic enzymes spermidine/spermine N1-acetyltransferase 1 (SAT1) and polyamine oxidase (PAOX), resulting in increased reactive oxygen species (ROS) accumulation, lipid peroxidation, and mitochondrial dysfunction. These changes were associated with suppression of the AMPK/ACC pathway, resulting in increased intracellular triglyceride (TG) accumulation. Conversely, treatment with the ODC1 inhibitor DFMO or knockdown ODC1 markedly alleviated oxidative stress and lipid accumulation. Furthermore, OR supplementation failed to reverse oxidative stress and adipogenesis following ODC1 knockdown, indicating that its metabolic effects are largely dependent on ODC1 activity. Taken together, our findings reveal that ODC1-mediated polyamine synthesis links SAT1/PAOX-associated ROS production to AMPK/ACC and increased lipid accumulation, highlighting ODC1 as a potential therapeutic target for obesity and lipid metabolic disorders.

Post-thaw quality of canine spermatozoa exposed to hydroxychalcones: a double-edged sword.

A cascade catalytic Zr-TCPP(Fe)/cys/Au nanoplatform for ferroptosis-mediated chemodynamic therapy in triple-negative breast cancer.

The key regulator of ferroptosis: HIF-1α and its complex roles and treatment strategies in related diseases.

Dual organelle targeting type I/II photosensitizer triggers ferroptosis-like/apoptosis for photodynamic immunotherapy.

Lipid peroxidation marker malondialdehyde is an independent determinant of hepatitis B vaccine response in hemodialysis patients.

Trifluoperazine induces ferroptosis in acute myeloid leukemia by suppressing the Nrf2/SLC7A11/GPX4 axis.

A smart polymer-based nanoplatform potentiates cancer ferroptosis-immunotherapy via perturbing metabolic compensation.

Lipidized deferoxamine nanomedicines (DFOsomes) against iron overload.

Cardiomyopathy, like other major cardiovascular diseases, is becoming increasingly prevalent and represents a growing public health challenge. Although both genetic and acquired factors contribute to its development, obesity and diabetes remain among the most significant modifiable risks. These conditions share key pathological features, including oxidative stress, inflammation, and elevated lipid peroxidation, all of which can disrupt cellular metabolism and function. Lipid oxidation products, irrespective of their origin, are characterized by increased oxygenation and hydrophilicity compared with their nonoxidized precursors. These properties confer high chemical reactivity toward cellular macromolecules, enabling the formation of covalent protein adducts that alter protein structure and function. Consequently, accumulation of excess lipid oxidation products initiates cytotoxic processes that disrupt mitochondrial homeostasis, potentially impairing cardiomyocyte function and contributing to broader cardiovascular pathology. Although lipid peroxidation frequently accompanies oxidative stress and inflammation, the mechanistic interrelationships among these processes in cardiomyopathy remain poorly defined. This narrative review synthesizes current evidence on the role of lipid peroxidation in cardiomyopathy, with particular emphasis on emerging insights into its interactions with oxidative stress and inflammatory pathways. Furthermore, it examines the impact of lipid oxidation products on mitochondrial dysfunction and cardiomyocyte viability, as well as their role in promoting cardiac fibroblast activation and myocardial fibrosis, all of which are key processes underlying the initiation and progression of cardiomyopathy.

Maternal infections can have profound effects on embryonic heart development, yet the precise pathways through which these impacts manifest are still largely unexplored. This research explores the influence of maternal exposure to lipopolysaccharide (LPS) and polyinosinic-polycytidylic acid [Poly(I:C)] on metabolic profiles and mitochondrial function of offspring. At embryonic day 16.5, pregnant female C57BL/6J mice received either LPS or Poly(I:C) treatment. Human induced pluripotent stem cells were differentiated into cardiomyocytes (hiPSC-CMs) to evaluate the effects of various interventions on cardiomyocyte differentiation. mRNA sequencing and untargeted metabolomics were performed to analyze metabolic alterations. The findings from mRNA sequencing indicated that both LPS and Poly(I:C) caused metabolic pathway disturbances in the offspring's heart, with differentially expressed genes enriched in lipid, energy, and amino acid metabolism. Additionally, untargeted metabolomics showed a notable elevation in polyunsaturated fatty acids following LPS or Poly(I:C) treatment. Moreover, both LPS and Poly(I:C) treatment significantly impaired mitochondrial function, increased reactive oxygen species, and heightened lipid peroxidation within offspring mouse hearts. Mitochondrial dysfunction was mitigated through the application of antioxidant agents, such as N-acetylcysteine and ferrostatin-1. During hiPSC-CM differentiation, Poly(I:C) treatment led to similar mitochondrial dysfunction, while LPS treatment had minimal effects on ATP levels and lipid peroxidation. These findings indicate that maternal infection impairs metabolic signaling and mitochondrial function in the developing heart, with oxidative stress and lipid peroxidation playing key roles in these effects.

Effects of benzo[a]pyrene on the lipid peroxidation and gene expression in the hepatopancreas and gill of Marsupenaeus japonicus.

Mild hypothermia alleviates ferroptosis in kidney ischemia-reperfusion injury via the glycolysis-lactate-HMGB1 lactylation axis.

NCOA4-dependent ferritinophagy: A key mechanism of selenium deficiency-induced ferroptosis and porcine phlebitis via the AMPK-mTOR pathway.

Ferroptosis exerts a recognized role in the pathogenesis of acute kidney injury (AKI) and is considered a critical target for improving its prognosis. Emerging evidence indicates that ferroptosis serves a pivotal role in pathogenesis of AKI and targeting ferroptosis provides a promising therapeutic strategy in treatment of AKI. In the present study, ligustroflavone (LIG), which is a flavonoid with oral activity extracted from Ligustrum lucidum, was found to inhibit ferroptosis through activation of nuclear factor erythroid 2‑related factor 2 (NRF2) via inhibition of GSK3β in vivo and in vitro. In vivo, cisplatin (CDDP) and ischemia‑reperfusion injury (IRI)‑induced murine models of AKI were constructed to evaluate the possible effects of LIG. In vitro, the protective effects of LIG were assessed in cultured mouse renal proximal tubular epithelial cells (TKPTs). Immunostaining, reverse transcription‑quantitative PCR, western blot and lipid peroxidation assays were performed to detect renal tubular injury and ferroptosis. The results of the present study demonstrated that LIG administration significantly ameliorated CDDP or IRI induced renal damage in mice. Additionally, administration of LIG significantly ameliorated lipid peroxide accumulation and inhibited ferroptosis in the kidneys of AKI mice. In vitro, LIG treatment markedly ameliorated CDDP‑induced lipid peroxidation and ferroptosis in cultured TKPTs via GSK3β inhibition and NRF2 activation. Furthermore, knockout of GSK3β also protected against CDDP‑induced cell death and LIG exerted no additional protective effects in GSK3β‑knockout TKPTs. Together, the present findings offer a new potential strategy for AKI therapies by targeting ferroptosis.

Ferroptosis, an iron-dependent regulated cell death modality driven by lipid peroxidation (LPO) and mitochondrial dysfunction, represents a promising therapeutic target for tumors, given cancer cells' elevated iron demand, reactive oxygen species (ROS) levels, and reliance on glutathione peroxidase 4 (GPX4) for redox homeostasis. While single-atom nanozymes (SANs) have emerged as potent catalytic tools for ROS-driven ferroptosis induction, their efficacy is hampered by the abundant glutathione and ROS-scavenging GPX4, which suppress sustained LPO accumulation. To address this bottleneck, we engineer a proof-of-concept Fe-based SAN (Fe-SAN) with well-defined Fe-N4 active sites and further encapsulate the GPX4 inhibitor Fin56 to construct the Fe-SAN@F nanoplatform. Fe-SAN@F showed dual catalytic activities: robust peroxidase-like activity that converts endogenous hydrogen peroxide into cytotoxic •OH to trigger LPO and glutathione oxidase-like activity that depletes intracellular GSH to inactivate GPX4. Meanwhile, the loaded Fin56 exerts synergistic GPX4 inhibition, amplifying the ROS cascade. In vitro and in vivo assays confirm that Fe-SAN@F induces irreversible tumor ferroptosis via the combined effects of LPO accumulation, GSH depletion, and GPX4 inactivation, effectively suppressing tumor proliferation. This work establishes a novel SAN-based catalytic therapy paradigm for remodeling the TME and boosting ferroptosis, providing a rational design strategy for next-generation precision antitumor nanozymes.

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy with limited therapeutic options. This study investigated the role of dipeptidyl peptidase-4 (DPP4) in regulating ferroptosis through its interaction with long-chain acyl-CoA synthetase 4 (ACSL4) in PDAC. DPP4 expression was significantly downregulated in PDAC tumor tissues compared with paired adjacent non-tumorous tissues from 56 patients. In vitro, DPP4 overexpression in PDAC cell lines inhibited cell proliferation, induced G1-S cell cycle arrest, impaired mitochondrial respiration, and markedly sensitized cells to erastin-induced ferroptosis. This sensitization was characterized by elevated unstable iron pools, increased lipid reactive oxygen species (ROS) and malondialdehyde levels, decreased glutathione and GPX4 expression, and ferroptotic mitochondrial morphology. These effects were specifically rescued by ferroptosis inhibitors. In an orthotopic PDAC mouse model, erastin treatment suppressed tumor growth and proliferation more effectively in wild-type mice than in DPP4-knockout mice, with reduced lipid peroxidation in knockout tumors. Mechanistically, DPP4 directly bound ACSL4, stabilized ACSL4 protein by inhibiting its ubiquitin-mediated degradation, and promoted ACSL4-dependent lipid peroxidation. ACSL4 knockdown rescued DPP4 overexpression-induced ferroptosis and lipid ROS accumulation. These results demonstrate that DPP4 acts as a positive regulator of ferroptosis in PDAC by stabilizing ACSL4, highlighting the DPP4-ACSL4 axis as a potential therapeutic target to enhance ferroptosis-based strategies against this aggressive cancer.

Baseline and long-term changes in phthalate exposure are differentially associated with lipid peroxidative but not DNA oxidative stress in adolescents and young adults: A 10-year prospective cohort study.

Endogenous oxidized phospholipid POVPC triggers pulmonary epithelial ferroptosis in acute lung injury and is restrained by RCN3.

Hepassocin drives EGFR-dependent endothelial atherogenic activation via NOX1/ROS amplification and p38 signaling.