Search Results (604)

This study evaluated the quality attributes of Protected Designation of Origin (PDO) Erzincan Tulum cheese by comparing control cheeses made with Kemah spring salt (KS) to those made with Sivas spring salt (SS), Çankırı rock salt (CS), and a low-sodium salt (rock salt–KCl blend, 50:50, LNaS). Cheeses were ripened at −2 to 0 °C for 120 days. Analyses included chemical composition, mineral profile, proteolysis, lipolysis, fatty acid composition, volatile compounds, and sensory properties. During ripening, dry matter and pH increased significantly (p < 0.05). Mineral content varied by salt type: LNaS had higher potassium and lower sodium, KS-C had the highest sodium and phosphorus, and SS-C the highest magnesium (p < 0.05). Proteolysis increased in all samples, with the highest levels in LNaS (p < 0.05). Lipolysis increased in all samples (p < 0.05), with CS-C showing the highest free fatty acid (FFA) content. Fifty volatile compounds were identified; carbonyl compounds were highest in LNaS-C and esters were highest in SS-C. Sensory evaluation showed that CS-C had the highest overall acceptability score and SS-C the lowest (p < 0.05). CS-C outperformed the control in sensory quality, and LNaS-C achieved similar sensory acceptance without compromising quality. Salt content and type were identified as critical factors in determining the authenticity of PDO Erzincan Tulum cheese. Full article

Insulin resistance (IR) is the underlying pathogenic mechanism for Type 2 Diabetes Mellitus, which is interconnected with Fatty Liver Disease. To investigate the molecular mechanisms by which different metabolic triggers contribute to hepatic IR onset, we exposed human HepG₂ hepatocytes to varying glucose concentrations (25–50 mM), and/or insulin (1 nM), and a free fatty acid mixture (0.3 mM), mimicking moderate or severe hyperglycemia, hyperinsulinemia, and steatosis. Glucose consumption, glycogen and lipid droplet (LD) accumulation, gene expression, oxidative stress, and insulin signaling were assessed. Under severe hyperglycemia, both insulin and fatty acids decreased glucose consumption, whereas under moderate hyperglycemia, only insulin had this effect. Glycogen accumulation was increased across all treated conditions. Both insulin and fatty acids triggered steatosis and downregulated PPARγ and SIRT1 mRNA, with insulin increasing LD number, while FFAs increased both LD number and size. All conditions enhanced ROS production, resulting in oxidative stress, but with differences in antioxidant enzyme response. Insulin receptor expression was reduced by insulin and FFAs under moderate hyperglycemia but increased by these stimuli under severe hyperglycemia. Both stimuli enhanced AKT phosphorylation under both hyperglycemic conditions. We conclude that different triggers cooperate in promoting hepatic IR through distinct molecular and signaling mechanisms, suggesting that effective treatments may need to target multiple pathways simultaneously. Full article

Horse mackerel is nutritionally valuable but highly prone to quality loss during chilled storage because its PUFA-rich lipids readily oxidize in comminuted products. Therefore, clean-label strategies are required to delay oxidation and spoilage. This study evaluated the effect of adding sea fennel (Crithmum maritimum), either as a plant homogenate incorporated at 5% (P-5%), 10% (P-10%) and 20% (P-20%) or as a dried polyphenolic extract at 0.25% (E-0.25%), 0.5% (E-0.5%), and 1% (E-1%), on the shelf-life of horse mackerel meatballs stored at 4 °C. Lipid oxidation, including free fatty acids (FFA), peroxide value, conjugated dienes, and thiobarbituric acid reactive substances (TBARS), antioxidant activity (ABTS and FRAP analyses), color (CIELAB color space), pH, total volatile basic nitrogen (TVB-N), spoilage-associated microbial groups, and volatile profiles were monitored during storage. Sea fennel reduced secondary oxidation compared to the control, with P-20% showing the lowest TBARS, corresponding to an approximately five-fold decrease compared with the control, and E-1% showing the clearest suppression of oxidation-derived aldehydes in the volatile fraction. The incorporation of either the plant homogenate or the extract reduced microbial growth, particularly that of Pseudomonas spp., while lactic acid bacteria counts increased during storage. This contributed to extend the microbiological shelf life of P-20% and E-1% by approximately 3 days. P-20% and E-1% also showed lower pH and TVB-N values over time. Overall, sea fennel improved the oxidative stability and early microbial control of refrigerated horse mackerel meatballs. However, whole-plant incorporation requires further optimization to balance matrix effects, quality evolution, and potential sensory changes. Full article

Metabolic dysfunction-associated steatohepatitis (MASH) is a severe, progressive liver disease lacking effective therapies. Disulfiram (DSF), an FDA-approved medication for alcohol dependence, exhibits diverse biological activities beyond its primary indication. This study aimed to evaluate whether DSF holds intervention promise for MASH and to unravel the underlying molecular mechanism. The efficacy of DSF was assessed in a mouse model of MASH induced by a choline-deficient, L-amino acid-defined diet, as well as in hepatocytes exposed to free fatty acids (FFAs) to trigger lipotoxicity. RNA-seq analysis combined with bioinformatic approaches was performed to identify key pathways and hub genes. Mechanistic validation was carried out using Western blotting and qPCR. Computational predictions suggested that DSF may influence insulin resistance, inflammation, autophagy-related markers, and lipid metabolism. In FFAs-treated hepatocytes, DSF administration dose-dependently reduced lipid accumulation and lipotoxicity. Consistently, in MASH mice, DSF administration significantly lowered elevated serum ALT (35%) and AST (40%) levels and the absolute hepatic triglyceride content (reduced from 1 to 0.5 μg/mg protein), and markedly attenuated hepatic steatosis, inflammation, fibrosis, and oxidative stress. Of note, RNA-seq analysis revealed that DSF modulated autophagy-related pathways and identified Aurora kinase A (AURKA) as a central downregulated hub gene. Mechanistically, DSF suppressed AURKA expression, which in turn led to changes in autophagy-related markers. These changes in autophagy-related markers were functionally coupled to a reduction in lipotoxicity. Collectively, DSF alleviates MASH by inhibiting AURKA, thereby relieving AURKA-mediated suppression of autophagy-related markers, which was associated with diminishing lipotoxicity, and ultimately achieving broad suppression of disease progression. Thus, DSF represents a promising hepatoprotective candidate for the intervention of MASH. Full article

The present research investigated the effects of two pork back-fat concentrations (30% fat, FAT30, and 40% fat, FAT40), two sodium chloride levels (2.4% and 2.6%), and two starter culture combinations (Lactobacillus curvatus/Staphylococcus xylosus; LAB6, and Lactobacillus sakei/Staphylococcus xylosus; LAB8) on ripened ostrich salami. Salami samples were formulated without nitrite and nitrate, which aligns with consumer demands for healthier, cleaner-label meat products. It is specified that the present experiment is structured with a single-batch-per-treatment combination: this was due to structural processing limitations in the production facility, which was an artisanal laboratory and not an industry plant. After 10 weeks of ripening, FAT30 salami showed higher values of pH, salt content, water-phase salt (WPS), α-tocopherol, free fatty acids (FFA), and secondary lipid oxidation products (TBARS) compared with FAT40 salami. Conversely, FAT40 salami exhibited higher water activity (a_w), moisture-to-protein ratio (M:P), conjugated dienes (CD; primary lipid oxidation products), and non-protein nitrogen (NPN) than FAT30 salami. Both NaCl concentration and starter culture type influenced several of the measured variables. Specifically, salami containing 2.4% salt exhibited higher FFA and CD values than the formulation containing 2.6% salt. Likewise, the LAB8 starter culture resulted in higher CD and NPN levels compared with LAB6. Fat inclusion level significantly affected sensory characteristics. FAT40 salami exhibited greater intensities of gamy, metallic, fatty, and moldy flavors, as well as higher overall off-flavor intensity, tenderness, and juiciness. In contrast, FAT30 salami was characterized by greater cohesiveness and a more pronounced ripening flavor. The 2.6% sodium chloride treatment resulted in greater color homogeneity, higher odor intensity, and stronger rancid notes, while reducing the perception of metallic, fatty, and moldy flavors compared with the 2.4% treatment. Salami inoculated with LAB6 exhibited a higher intensity of off-flavors than the formulation produced with LAB8. Moreover, several significant interactions among the three experimental factors were observed. After 20 weeks of ripening, the effects observed after 10 weeks for most physicochemical parameters were largely maintained. However, FFA and CD concentrations (both below the limit of quantification) no longer differed between the two fat inclusion levels. Sensory evaluation revealed that the differences between FAT30 and FAT40 in undesirable flavor attributes disappeared over time, whereas the perception of ripening and maturity became even more pronounced in FAT30 salami. Regarding FA composition, FAT30 salami contained higher proportions of saturated FA and polyunsaturated FA, whereas FAT40 salami was characterized by a higher monounsaturated FA content and more favorable lipid quality indices. Full article

Metabolic dysfunction-associated steatohepatitis (MASH) is a progressive liver disease with limited treatment options. Here, we demonstrate that fucoxanthin (FUCO), a natural marine carotenoid, attenuates free fatty acid (FFA)-induced hepatocellular steatosis and inflammatory responses in vitro by targeting the EGR2-CD36 axis (EGR2, early growth response protein 2; CD36, cluster of differentiation 36). In FFA-induced hepatocyte models (HepG2, Hep3B, and AML12), FUCO significantly reduced lipid accumulation and inflammatory markers without cytotoxicity. Mechanistic studies revealed that FUCO specifically inhibited fatty acid uptake and transport by downregulating CD36, while triglyceride (TG) degradation remained unaffected. RNA sequencing identified EGR2 as a master regulator induced by FFA and suppressed by FUCO. Functional validation showed that EGR2 overexpression completely blocked FUCO’s lipid-lowering effects and restored CD36 expression, confirming that FUCO acts through EGR2-dependent CD36 inhibition. Bioinformatic analysis further supported EGR2-mediated regulation of CD36 via tumor necrosis factor (TNF) and sterol regulatory element-binding factor (SREBF) pathways. Collectively, our findings establish EGR2 as a critical molecular target for FUCO and provide mechanistic insights that may support its further evaluation in preclinical models for MASH therapy. Full article

Microalgal lipids are promising sustainable feedstocks for high-value functional ingredients. However, the influence of cultivation-driven lipid composition on enzymatic conversion remains poorly understood. This study integrated cultivation strategy and enzymatic upgrading to tailor Neochloris oleoabundans lipids for mono- and diacylglycerol (MAG and DAG) production. Heterotrophic cultivation achieved a maximum dry biomass concentration of 2.78 ± 0.14 g L⁻¹, whereas autotrophic cultivation reached 0.39 ± 0.01 g L⁻¹, confirming the superior biomass productivity of heterotrophic metabolism. Lipid fractions obtained under both trophic conditions were characterized and subjected to glycerolysis catalyzed by Novozym 435 under a 5:1 glycerol-to-oil ratio for 16 h. Heterotrophic oils, characterized by triacylglycerol-rich and low-free fatty acid (FFA) profiles, achieved higher MAG + DAG conversion (45%), while autotrophic oils reached 43% conversion despite elevated FFAs and polar lipids. The presence of FFAs, pigments, and phospholipids in non-refined microalgal oils influenced catalytic behavior, reducing conversion efficiency and favoring competing esterification and hydrolysis pathways. These findings demonstrate that substrate purity, acylglycerol distribution, and cultivation-specific lipid architecture strongly affect lipase performance, highlighting oil refining and cultivation optimization as key strategies for improving sustainable MAG and DAG production. Full article

Background/Objectives: Endometrial cancer (EC) is the most prevalent gynecological malignancy in developed countries, yet no clinically validated noninvasive screening biomarker exists. Fatty acid metabolic reprogramming is a hallmark of cancer that produces measurable changes in systemic free fatty acid (FFA) profiles. We aimed to identify serum FFAs altered in EC and evaluate their potential as early diagnostic biomarkers. Methods: Gene expression of fatty acid metabolic enzymes in EC tissues was assessed using public databases. Serum levels of 19 FFAs were quantified by gas chromatography–mass spectrometry in 72 patients with EC and 84 healthy donors. A two-variable diagnostic model was constructed using logistic regression and validated in an independent dataset. Results: Multiple fatty acid metabolic enzymes involved in de novo synthesis were upregulated in EC tissues as early as stage I, while enzymes mediating fatty acid uptake and release were downregulated. Serum levels of palmitoleic acid, oleic acid and dihomo-γ-linolenic acid were significantly elevated, whereas arachidic acid and arachidonic acid were significantly decreased in patients with EC from stage I onward. A diagnostic model combining palmitoleic acid and arachidonic acid achieved an area under the receiver operating characteristic curve of 0.9674, with a sensitivity of 91.3% and specificity of 96.4% in the validation dataset, including for stage I disease, and was independent of body mass index, age, metastasis status, and family history. Conclusions: Serum FFA profiling represents a promising noninvasive strategy for early EC detection, with the potential to complement existing diagnostic methods. Full article

This study characterized the basic structure of partridge tea leaves polysaccharides and comparatively analyzed the in vitro lipid-lowering activity of total partridge tea polysaccharide (PTPS) and its two purified homogeneous fractions, namely PTPS-I (13,560 Da) and PTPS-III (30,935 Da). In terms of structural composition, PTPS-I and PTPS-III share identical monosaccharide types but differ significantly in monosaccharide proportions, glycosidic linkages and backbone structures. In vitro experiments demonstrated that PTPS, PTPS-I, and PTPS-III could effectively reduce intracellular lipid levels and oxidative stress in free fatty acids (FFA)-injured L02 cells and alleviate the decline of mitochondrial membrane potential in damaged hepatocytes. At the high concentration of 400 μg/mL, PTPS-III showed a superior effect in reducing triglyceride (TG) content compared with the other two samples, with the value reaching 0.31 ± 0.024 mmol/mg prot. Additionally, 400 μg/mL PTPS markedly decreased total cholesterol (TCHO) content and enhanced superoxide dismutase (SOD) activity, which were 0.55 ± 0.039 mmol/mg prot and 29.92 ± 0.22 μmol/mg prot, respectively. PTPS-I of 400 μg/mL significantly reduced malondialdehyde (MDA) content to 1.31 ± 0.288 μmol/mg prot and inhibited the decline of mitochondrial membrane potential (MMP) by 9.67%. The three polysaccharide fractions could elevate the mRNA expression of Nrf2, NQO1 and HO-1 in the Nrf2/HO-1 signaling pathway and the gene expression of PPARα, CPT-1 and ACOX1 in the lipid metabolism pathway, and ultimately regulate lipid accumulation in L02 cells. This study validated the in vitro antilipid activities of partridge tea leaves polysaccharide and provided fundamental data for research on its bioactivity and functional components. Further in vivo assays and mechanism exploration will be conducted to evaluate its potential application in fatty liver intervention product development. Full article

Background/Objectives: Type 2 diabetes (T2D)-associated sarcopenia is characterized by impaired insulin signaling, lipotoxicity, oxidative stress, and progressive muscle loss. Although liraglutide improves glucose control and reduces lipid burden, its ability to preserve muscle integrity under diabetic lipotoxic conditions remains limited. This study investigated whether β-hydroxy-β-methylbutyrate (HMB) could enhance liraglutide-mediated protection against high-glucose plus free fatty acid (HG+FFA)-induced injury in skeletal muscle cells. Methods: Differentiated C2C12 myotubes were exposed to HG+FFA to establish a sublethal lipotoxic model and treated with liraglutide, HMB, or their combination. Cell viability, lipid accumulation, myotube morphology, insulin signaling, glucose uptake, mitochondrial function, reactive oxygen species (ROS), antioxidant gene expression, and atrophy-related signaling were assessed. Results: HG+FFA induced marked lipid droplet accumulation, impaired insulin signaling, reduced glucose uptake, disrupted mitochondrial membrane potential, increased ROS production, suppressed antioxidant gene expression, and promoted an atrophic phenotype characterized by increased atrogin-1 and MuRF1 and reduced myogenic markers. Liraglutide alone reduced large lipid droplets and partially improved insulin signaling but showed limited efficacy in preserving the myotube phenotype. HMB alone exerted modest effects on lipid accumulation but preserved myotube area. Notably, combined HMB and liraglutide treatment more effectively reduced lipid burden, restored insulin signaling and glucose uptake, attenuated mitochondrial dysfunction and oxidative stress, restored antioxidant gene expression, and preserved MyHC-positive area and myotube diameter while suppressing atrogin-1/MuRF1 activation. These protective effects were largely attenuated by rapamycin, indicating at least partial dependence on mTOR-associated signaling. Conclusions: Overall, HMB and liraglutide exert complementary protective effects against diabetic lipotoxic and atrophic stress, supporting the potential utility of this combination strategy for T2D-associated sarcopenia. Full article

One-lung ventilation (OLV) is performed during lung surgeries by ventilating a single lung, while collapsing the operative lung to provide surgical exposure within the thoracic cavity. While a lung-protective ventilation strategy is recommended during OLV, increasing the fraction of inspired oxygen (FiO₂) or tidal volume (V_T) may be required to prevent hypoxemia during surgery. Unfortunately, these increases are associated with postoperative lung injury. Using a porcine model of OLV, our project aims to determine if high FiO₂ or V_T during OLV contributes to elevation of pro-inflammatory lipid mediators postoperatively. Fifteen three-month-old farm-bred pigs underwent left upper lobectomy requiring OLV. Pigs were exposed to one of three ventilation parameters: normoxic low V_T lung-protective ventilation LPV-NO, n = 5, FiO₂ < 50%, V_T = 6 mL/kg), hyperoxic lung-protective ventilation (LPV-HO, n = 5, FiO₂ >100%, V_T = 6 mL/kg), or normoxic high V_T (injurious mechanical ventilation) (IMV, n = 5, FiO₂ < 50%, V_T = 10–12 mL/kg). Arterial plasma was collected before and after OLV, and lipids were detected via LC-MS-MS. Lipidomic analysis demonstrated a statistically significant increase (FC = 2, p ≤ 0.05) in lysophosphatidylethanolamines (LPE 18:3, LPE 20:4, LPE 18:2, LPE 22:6), free fatty acids (FFA 20:4), phosphatidylserine (PS 38:5), lysophosphatidylcholine (LPC 18:1, LPC 18:3, LPC 22:6), triglyceride (TG 18:2-18:2-20:4), free fatty acids (FFA 20:5), linoleyl-carnitine molecules (C18-2 Linoleoyl Carnitine), and phosphatidylethanolamines (PE 36:5) in LPV-HO. IMV resulted in a significant increase (FC = 2, p ≤ 0.05) in triglyceride (TG 18:2-18:2-20:4), diglyceride (DG 18:1-20:4, DG 16:0-20:4), linoleyl-carnitine molecules (C18-2 Linoleoyl Carnitine), and free fatty acids (FFA 20:5). There was no significant change in lipid biomarker levels following LPV-NO post-surgery. Our lipidomic analysis supports that both high FiO₂ and V_T contribute to systemic lipid metabolic derangements. Lipids that were elevated in LPV-HO and IMV are associated with multiple inflammatory pathways implicated in lung injury. This suggests that intra-operative anti-inflammatory therapies targeted to these lipid pathways may reduce or prevent postoperative pulmonary complications after lung surgery. Full article

Polycystic ovary syndrome (PCOS) is frequently accompanied by visceral obesity, insulin resistance, low-grade chronic inflammation, and metabolic syndrome (MetS). These alterations promote significant dysfunction in adipose tissue and liver metabolism through cytokine production. Growing evidence indicates that the interaction between hepatokines and adipokines plays a central role in the development of metabolic and hepatic abnormalities in women with PCOS. This narrative review was conducted to analyze the relationship between adipose tissue dysfunction and liver metabolic impairment in women with PCOS, emphasizing the involvement of hepatokines and adipokines in insulin resistance, inflammation, hepatic steatosis, hepatic fibrosis and MetS. From this perspective, contemporary clinical, biochemical, and molecular studies were reviewed to evaluate how adipocyte-derived factors and hepatocyte-derived cytokines influence metabolic homeostasis in the liver and adipose tissue in women with PCOS. Increased visceral adiposity in PCOS enhances the release of free fatty acids (FFAs) to the liver, resulting in hepatotoxicity, oxidative stress, and hepatic inflammation. Several hepatokines, including fetuin-A, angiopoietin-like protein 3 (ANGPTL3), selenoprotein P(Sep-P), and hepassocin (HPS), show abnormal circulating levels in PCOS and are strongly associated with insulin resistance, dyslipidemia, and progression to hepatic steatosis. In contrast, fibroblast growth factor 21 (FGF-21), follistatin, and interleukin (IL-6) may exert dual effects. Adipokines, such as resistin, visfatin, apelin, and retinol-binding protein 4 (RBP-4), contribute to chronic inflammation, impaired glucose metabolism, androgen excess, and hepatic steatosis and fibrosis. Some of these adipokines, such as leptin and vaspin, may exert both beneficial and detrimental effects, while others, including chemerin and omentin, appear to play predominantly beneficial roles in metabolism. Reduced adiponectin-to-leptin levels further aggravate metabolic dysfunction. These changes indicate that adipose tissue–liver crosstalk is a key mechanism linking PCOS and MetS. Overall, metabolic disturbances in PCOS are strongly mediated by dysregulated communication between adipose tissue and the liver. Altered hepatokine and adipokine profiles contribute to insulin resistance, liver dysfunction, hypertension and the development of MetS in women with PCOS. Understanding these intricate interactions may support the early identification of high-risk patients and the development of targeted therapeutic strategies. Full article

Human milk cream, a lipid-rich fraction obtained during milk defatting, is typically discarded despite its potential for individualized nutritional strategies. This study evaluated the effects of Holder pasteurization (HoP) and storage conditions (refrigeration and freezing) on the microbiological profile and lipid stability of human milk–derived cream. Cream fractions from six mothers of preterm infants were analyzed for bacterial counts using Columbia Nalidixic Acid and MacConkey agar, with isolate identification by MALDI-TOF MS, and for lipid stability through free fatty acids (FFAs), triacylglycerol (TAGs) composition by GC-FID, and peroxide values (PV) determined by a rapid photometric method. Raw cream showed stable total bacterial counts across storage conditions, with a reduction in Gram-negative bacteria after freezing, while HoP samples exhibited no detectable bacterial growth. Lipolysis was significantly higher in raw cream, with increased FFAs after 72 h refrigeration, whereas HoP samples maintained lower and more stable FFA levels. TAG profiles remained largely stable under refrigeration but were significantly altered during frozen storage in raw samples, suggesting membrane disruption and selective hydrolysis; these changes were attenuated in HoP samples. PV increased over time in both groups, indicating progressive primary lipid oxidation, although values remained within moderate ranges. Overall, HoP improved microbiological safety and lipid stability, supporting the potential use of human milk cream as a controlled lipid source for individualized fortification in preterm infants. Full article

Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by abnormal hepatic lipid accumulation and is frequently driven by factors such as a high-fat diet (HFD). Total flavonoids of Apocynum venetum (TFAV), the bioactive constituents of a traditional medicinal plant, have demonstrated antioxidant and lipid-modulating properties. However, their therapeutic potential against MASLD and the underlying mechanisms are not explored. This study aims to evaluate the ameliorative effects of TFAV on HFD-induced MASLD utilizing both in vivo animal and in vitro cellular models. Methods: C57BL/6J were allocated to control, high-fat diet (HFD), TFAV (100 mg/kg/day), and TFAV intervention groups (25, 50, and 100 mg/kg/day). In vitro, WRL68 hepatocytes were stimulated with free fatty acids (FFAs) to establish a cellular model of steatosis. Liver function, serum lipid profiles, hepatic histopathology, and the AMPK signaling pathway were assessed. Results: TFAV intervention significantly improved serum biochemical profiles in the animal models; for instance, co-treatment with 100 mg/kg/day TFAV and HFD reduced TC, TG, and LDL-C levels by 20.59%, 45.26%, and 38.24% respectively (p < 0.05), and effectively alleviated hepatic steatosis and hepatocyte ballooning. Furthermore, TFAV markedly inhibited intracellular reactive oxygen species (ROS) levels and activated the AMPK signaling pathway (p < 0.05). This was accompanied by the downregulation of SREBP-1c and ACC expression (p < 0.05), as well as the upregulation of ATGL and CPT1α expression (p < 0.05). Conclusions: These results demonstrates that TFAV remodel hepatic lipid homeostasis by activating the AMPK signaling pathway, and exerting significant preventive and protective effects against the progression of HFD-induced MASLD in vivo. Full article

Objective: This study investigated the effects of ginsenoside F1 on lipid metabolism using cell-based assays combined with lipidomics. Methods: The optimal non-cytotoxic concentration of ginsenoside F1 was determined by the CCK-8 assay. A hyperlipidemic cell model was established by inducing HepG2 cells with free fatty acids (FFAs). Model cells were treated with ginsenoside F1 (0.2 µM, 0.8 µM, and 3.2 µM) or simvastatin (3.2 µM, positive control) for 24 h. Intracellular lipid accumulation was determined by measuring absorbance at 510 nm, together with quantification of total cholesterol (TC) and triglyceride (TG) contents. Untargeted lipidomics was employed to explore alterations in the lipid profile and identify relevant metabolic pathways. Results: Compared with the model group, lipid deposition, total cholesterol, and triglycerides were significantly reduced by ginsenoside F1 (p < 0.05). A total of 110 differential metabolites, mainly phosphatidylinositol and phosphatidylcholines, were identified by lipidomics, with glycerophospholipid and ether lipid metabolism highlighted as the key regulated pathways. Potential roles of targets including Akt1, PPARG, and EGFR, as well as pathways related to cancer and lipid metabolism, were further indicated by network pharmacology and molecular docking. Conclusions: FFA-induced lipid disorders in HepG2 cells were alleviated by ginsenoside F1, potentially through the regulation of glycerophospholipid metabolism. Full article