The global prevalence of cognitive impairment is currently on the rising, with high-fat diet (HFD) being a significant contributing factor. Phyllanthus emblica Linn (PE) extracts possess potent antioxidant properties, enhance memory, and exert neuroprotective effects. However, the mechanisms by which Phyllanthus emblica Linn poly-phenols (PP) counteract HFD-induced cognitive decline remain poorly understood. In this study, C57BL/6J mice were fed an HFD with or without low and high doses of PP for 14 weeks. The effects of PP on metabolism, inflammation, cognitive function, and hippocampal histopathology were evaluated. 16S rRNA sequencing, network pharmacology, transcriptomics, and molecular docking were integrated to predict mechanisms, which were subsequently validated by qRT-PCR and Western blot. PP supplementation mitigated HFD-induced weight gain, insulin resistance, and peripheral and central inflammation. It also attenuated hippocampal neuronal damage and significantly improved learning and memory in behavioral tests. PP enhanced gut microbial alpha-diversity, increased the abundance of beneficial genera like Akkermansia and Allobaculum, and reduced the Firmicutes/Bacteroidetes ratio. This study also confirms, through faecal microbiota transplantation (FMT), that the gut microbiota is a key mediating target through which PP alleviates intestinal inflammation and improves HFDinduced cognitive decline. Integrative analysis identified the Calcium/cAMP signaling pathway as a key mediator. Molecular docking revealed a strong binding affinity between the PE compound luteolin and EGFR. Subsequent validation confirmed that PP treatment upregulated the mRNA and protein expression of key pathway components, HTR7, PRKACB, and GRIN2A, in the brain. In conclusion, PP alleviates HFD-induced cognitive impairment by remodeling the gut microbiota and upregulating the HTR7/PRKACB/GRIN2A axis within Calcium/cAMP signaling pathways, ultimately attenuating neuroinflammation.

L-Se-methylselenocysteine (L-SeMC) is a naturally occurring organic selenium compound with superior bioavailability and safety compared to inorganic forms. Although proposed to possess antitumor potential, its efficacy in hepatic tumor prevention and intervention remains poorly characterized. This study investigated the long-term preventive and short-term interventional effects of L-SeMC on hepatic tumor development in a mouse model. Tumor progression, oxidative stress, cytokine profiles, apoptosis-related gene and protein expression, and tumor cell apoptosis were comprehensively assessed. L-SeMC significantly inhibited tumor growth, with inhibition rates reaching 66.63% in the high-dose preventive cohort and 73.56% in the preventive-acute continuous intervention cohort. These effects were attributed to the enhancement of antioxidant defenses, as evidenced by increased levels of SOD, CAT, GPx, and GSH, and decreased MDA levels. Additionally, cytokine modulation was observed, with upregulation of IL-4, IL-10, TNF-α, and IFN-γ. Furthermore, apoptotic signaling was activated, marked by elevated levels of Bax, caspase-8/9, and an increased Bax/Bcl-2 ratio, corroborated by TUNEL staining. Remarkably, L-SeMC demonstrated these advantages without causing toxicity or exerting any detrimental effects on body weight or immune organ indices. Overall, the findings highlight L-SeMC as a food-derived bioactive compound capable of integrating antioxidant, immunomodulatory, and apoptotic mechanisms to suppress hepatic tumor progression. This work provides an experimental basis for developing L-SeMC-enriched functional foods and dietary strategies for hepatic tumor prevention.

Methionine-containing cyclolinopeptide ([1-9-NαC]-linusorb B2, CLB) and α-linolenic acid (ALA), two anti-inflammatory flaxseed constituents, were investigated for their combined vascular benefits. CLB-enriched orbitides were prepared for long-term high-fat diet (HFD)-fed mouse studies, while high-purity CLB monomer (>97%) was isolated via preparative chromatography for acute in vivo and cell-based assays. Structural confirmation and purity validation were achieved via mass spectrometry and liquid chromatography. CLB-enriched orbitides co-administered with ALA in HFD-fed mice reduced body weight gain, serum trimethylamine N-oxide (TMAO), dyslipidemia, and vascular inflammation, histologically confirmed by reduced pro-inflammatory mediators and endothelial repair. Purified CLB combined with ALA further demonstrated efficacy in alleviating TMAO-induced acute vascular inflammation in mice. Mechanistically, CLB enhanced ALA metabolism by upregulating key enzymes (lipoxygenases and cytochrome P450) and directly binding to their catalytic pockets. Combined effect loss upon enzyme inhibition confirmed ALA metabolic modulation as the key mechanism. These findings highlight CLB's role in amplifying ALA's efficacy to combat vascular inflammation.

This study focuses on Lacto-N-neotetraose (LNnT), a core component of human milk oligosaccharides. Although LNnT has been demonstrated to promote early intestinal development and maintain gut homeostasis, its protective mechanism against D-galactose-induced intestinal injury and associated cognitive impairment remains unclear. This investigation systematically examined the protective effects and underlying mechanisms of LNnT against D-gal-induced colonic damage and cognitive impairment in mice. The results demonstrated that LNnT not only significantly improved systemic physiological phenotypes and upregulated the expression of colonic tight junction proteins to repair the intestinal barrier, but also effectively enhanced learning and memory abilities in mice. Concurrently, LNnT reduced serum proinflammatory factor levels, elevated the anti-inflammatory factor IL-10, and alleviated oxidative stress. Furthermore, LNnT remodeled the gut microbiome structure by increasing microbial diversity, enhancing beneficial bacteria abundance, and promoting short-chain fatty acid production. Untargeted metabolomics analysis further revealed that LNnT corrected metabolic disturbances by regulating key sphingolipid molecules (ceramide, sphingosine, S1P) and the expression of related metabolic enzymes (ACER2, SphK2). In summary, this study suggests that LNnT mitigates intestinal injury and improves cognitive function, potentially through modulation of the gut microbiota-sphingolipid metabolism axis, although further causal validation is warranted. These findings provide a mechanistic foundation for future studies exploring its potential as a functional dietary ingredient.

This study integrates fluorescence resonance energy transfer (FRET) and small-angle X-ray scattering (SAXS) to elucidate, in real time, how triacylglycerol (TAG) self-assembly dynamics in human milk regulate digestion and absorption. Among three major human milk TAGs-1-oleoyl-2-palmitoyl-3-linoleoyl-glycerol (OPL), 1,3-dioleoyl-2-palmitoyl-glycerol (OPO), and 1,3-dilinoleoyl-2-palmitoyl-glycerol (LPL)-OPL showed ∼20% faster lipolysis and more rapid micelle formation (IRhB/IFITC stabilized 60 min earlier, RSD < 5%), likely due to its asymmetric sn-1,3 acyl chain structure. However, OPL-assembled micelles had ∼25% lower molecular packing density (qmax) and ∼ 20% lower interfacial stability (KPorod) than OPO/LPL. This "fast-assembly-loose-structure" profile led to ∼10% slower diffusion of OPL digestion products in mucus, suggesting that although OPL digests efficiently, its absorption is hindered by unstable self-assemblies that disintegrate in mucus. These findings reveal a previously unrecognized antagonism between digestion and absorption driven by lipid molecular structure, providing new insights into the design of lipid ingredients in infant formula.

The phospholipid composition of human milk and infant formula differs. To evaluate how the structure and distribution of phospholipid classes affect digestion and the bioavailability of fatty acids, our study employed simplified phospholipid-composition model emulsions comprising purified phosphatidylethanolamine (PE), phosphatidylcholine (PC), and sphingomyelin (SM), and phospholipid analogs mimicking human milk (HMPA) or infant formula (IFPA). In simulated infant gastrointestinal digestion, phospholipid hydrolysis and free fatty acid release followed the order PE > PC > SM. HMPA showed greater interfacial charge changes, faster phospholipid degradation, and higher fatty acid release than IFPA. In mice, it also produced higher dose-normalized serum AUCs for major fatty acids. These findings indicate that phospholipid class composition modulates digestion characteristics and the rate of fatty acid absorption. However, these purified models do not reproduce human milk or formula. Thus, the results should be interpreted as mechanistic evidence rather than direct infant nutritional outcomes.

The objectives of this study were to evaluate the antioxidant interactions and underlying mechanisms of the combinations of purple carrot anthocyanins extracts (PCAE) and red papaya carotenoids extracts (RPCE) using tert-butyl hydrogen peroxide (TBHP)-induced human umbilical vein endothelial cells (HUVEC). The results revealed that cyanidin-3-xylosyl (feruloyl glucosyl) galactoside (731.65 +/- 2.66 mu g/mg) and lycopene (787.50 +/- 5.73 mu g/mg) were the dominant anthocyanins and carotenoids in purple carrot and papaya, respectively. Cellular antioxidant assays, including cellular antioxidant activity (CAA) and antioxidant enzymes expression, reactive oxygen species (ROS) and malondialdehyde (MDA) levels, showed that in the combinations which contained more hydrophilic PCAE, the combinations would tend to show synergistic effects. When RPCE were in the majority, the combinations would tend to show antagonistic effects. Reverse transcriptase-PCR and Western blot analysis revealed the underlying mechanisms of synergistic/antagonistic antioxidant interactions were that they significantly inhibited intracellular ROS generation, exhibiting either synergistic/antagonistic effects on reducing mitochondrial ROS levels, restoring the mitochondrial membrane potential, and inhibiting the activity of the nicotinamide adenine dinucleotide phosphate oxidase 4. Meanwhile, they also reduced cellular ROS level via inhibition of the nuclear factor kappa-light-chain-enhancer of activated B (NF-kappa B) signaling pathway, to elevate the activities of antioxidant enzymes based on HUVEC cell model. The synergistic/antagonistic antioxidant effects of phytochemical combinations supported their potential as functional food ingredients for cardiovascular diseases prevention.

Pomegranate peel extract (PPE) shows limited potent antioxidant activity due to the presence of high levels of bound polyphenols and macromolecular ellagitannins that are poorly absorbed directly by the intestine. Enzymatic treatment could effectively facilitate the bioconversion of macromolecules into micromolecules, thereby enhancing antioxidant activity. Therefore, in this study, PPE was treated by tannase and beta-glucosidase to evaluate its in vitro antioxidant activity and protective effects on D-galactose-induced oxidative stress in mice. Compared to single-enzyme treatment, dual-enzyme-treated PPE exhibited the most pronounced enhancement in in vitro antioxidant activity. Further mass spectrometry analysis revealed that dual-enzyme treatment significantly converted macromolecular polyphenols, including punicalagin (41.23% of reduction), into micromolecules, such as gallic acid (471.88% of increase) and ellagic acid (101.71% of increase), which are tightly linked to enhanced antioxidant activity. The animal experiments showed that dual-enzyme-treated PPE most significantly alleviated the oxidative stress in mice via the activation of antioxidant enzymes. Furthermore, dualenzyme-treated PPE most notably up-regulated the gene expression levels of nuclear factor erythroid-derived 2related factor 2 (Nrf2) and its downstream antioxidant enzyme genes, such as heme oxygenase-1 (HO-1) and NAD(P)H quinone dehydrogenase 1 (NQO1) (230.23%, 94.24% and 95.38% of increase respectively) and their protein expression levels (195.92%, 91.97% and 197.64% of increase respectively). These findings indicate that the dual-enzyme-treated PPE may alleviate the oxidative stress via the activation of a Nrf2-related pathway. This work provides evidence for the enhancement of multi-enzyme combined treatment of PPE on antioxidant activity and potential applications in natural antioxidants and antioxidant nutraceuticals.

Medium- and long-chain triglycerides (MLCTs) in human milk play a critical role in infant nutrition. In this study, human milk-simulated MLCTs (HMS-MLCTs) were synthesized via lipase-catalyzed acidolysis. Lipozyme RM IM was identified as the optimal lipase. The reaction conditions were optimized as follows: temperature 60 °C, enzyme loading 10%, reaction time 4 h, substrate molar ratio 1:6, and free fatty acids molar ratio 2:8. Under those reaction conditions, the content of MLCT and MLL (containing one medium-chain fatty acid and two long-chain fatty acids) in HMS-MLCTs were 53.76% and 41.96%, respectively. The major MLCT species closely resembled those found in human milk. Furthermore, HMS-MLCTs exhibited greater thermal oxidative stability and a lower melting point compared to the substrate oil. Similarity evaluations indicated that HMS-MLCTs exhibited potential to bridge the compositional gap between human milk and infant formula in MLCTs. This study provides novel insights into the humanization of lipids for infant formula.

Based on the traditional Chinese medicine principle of “medicine-food homology”, a dairy-based meal replacement product, Herbal-Dairy Meal Replacement (HD-MR), was developed for the dietary intervention of non-alcoholic fatty liver disease (NAFLD). HD-MR was designed with an optimized nutritional composition: low in fat and sugar, high in protein, and enriched with various medicine and food homology substances such as kudzu root, Poria cocos, reed rhizome, ginseng, dandelion, Hovenia dulcis Thunb., and cordyceps flower. Bioactive components were extracted from these substances through an optimized enzymatic hydrolysis process. A six-week intervention study was performed in a high-fat diet (HFD)-induced NAFLD mouse model. Comprehensive analyses were performed, including serum biochemistry, histopathology, 16S rRNA sequencing, and quantification of short-chain fatty acids (SCFAs). HD-MR significantly alleviated hepatic steatosis, reduced serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglycerides (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C), while increasing high-density lipoprotein cholesterol (HDL-C) and improving histopathological liver injury. These positive effects appear to be mediated through the modulation of the gut microbiota-SCFA axis, characterized by an increased abundance of Verrucomicrobia, a reduced Firmicutes/Bacteroidota ratio, and enhanced production of beneficial SCFAs. HD-MR demonstrated hepatoprotective effects in NAFLD mice, potentially by regulating lipid metabolism and modulating the gut microbiota-SCFA axis. Thus, HD-MR may represent a promising dietary management strategy for patients with NAFLD.

This study aimed to enhance the nutritional value, functional performance, and storage stability of organic brown rice-based infant cereal by incorporating Microencapsulated Rice Bran (MRB). Unlike the direct addition of rice bran (RB), which often compromises sensory quality and reconstitution properties, RB was enzymatically treated with alpha-amylase and cellulase to achieve partial hydrolysis prior to microencapsulation, and then encapsulated using maltodextrin (MD), whey protein isolate (WPI), and phospholipids. This pretreatment facilitated structural breakdown and improved protein accessibility. The optimal microencapsulation conditions (MD:WPI = 1:1, 20 % wall addition, 1.5 % phospholipids) yielded stable emulsions with high encapsulation efficiency. Powder viscosity reduced from 27.67 cP to 19.67 cP, water solubility index increased from 16.75 % to 60.70 %, peroxide value lowered from 23.174 mmol/kg to 11.589 mmol/kg after storage, and gelatinization enthalpy significantly increased from 116.76 J/g to 228.02 J/g, indicating markedly improved flowability, oxidative, and thermal stability. When incorporated at 8 % into infant cereal, MRB not only significantly improved the nutritional composition (1.11-fold higher protein, 1.87-2.92-fold higher fat) with better sensory quality, reconstitution properties, and flowability compared to cereals with unencapsulated RB. In vitro digestion showed 1.10-fold higher protein and 1.07-fold higher starch digestibility, attributed to smaller particle size and enhanced enzymatic accessibility. Overall, this approach overcomes the key limitations of direct RB incorporation, offering a promising approach to developing nutrient-dense, high-quality infant foods.

Tannase is an industrial enzyme with broad application potential in areas such as the food industry. In this study, two tannase isoenzymes, SM-1-TA and SM-2-TA, were identified from Streptomyces avermitilis and comparatively analyzed for their bioinformatic and enzymatic properties. The optimal temperature for SM-1-TA and SM-2-TA was 35°C and 45°C, respectively, while their optimal pH was 7.0 and 8.0. Notably, SM-2-TA exhibited high thermal stability, retaining 40.03% residual activity after incubation at 40°C for 2 h. Most metal ions and chemical reagents inhibited the catalytic activity of both SM-1-TA and SM-2-TA. Meanwhile, compared to SM-1-TA, SM-2-TA demonstrated greater tolerance to organic reagents. When methyl gallate, propyl gallate, and tannic acid were used as substrates, the kcat/Km of SM-1-TA was 77.59, 63.53, and 198.31 s- 1 mM- 1, respectively, while those of SM-2-TA were 44.65, 23.43, and 473.67 s- 1 mM- 1, respectively. Molecular dynamics (MD) simulations suggested that the lower thermal stability of SM-1-TA may originate from its higher overall flexibility and pronounced local fluctuations within the residue region 100-150. The functional complementarity between SM‑1‑TA and SM‑2‑TA observed in this study highlights the ecological significance of isoenzymes in microbial adaptation to diverse environments. These findings not only provide insights into the functional divergence of isoenzymes but also establish a foundation for the future discovery and engineering of tannases with enhanced properties.

Proteins and amino acids are indispensable for infant growth and development; however, a systematic and quantitative synthesis of their global concentrations remains limited. This study conducted a systematic review, integrating data from 71 studies and 113,829 human milk samples. Meta-regression and subgroup analyses were used to quantify variations attributable to the lactation stage. Pooled mean concentrations were determined for total protein, total amino acids, and representative bioactive proteins, including lactoferrin and osteopontin. All components declined over lactation except osteopontin, which uniquely increased. Notably, the relative proportions of indispensable amino acids remained highly stable. Overall, these data could establish a consolidated, stage-resolved benchmark for the protein and amino acid composition of human milk.

In this study, four ages of pigeons (20 days, 2 months, 6 months, and 2 years) were comprehensively evaluated for their nutritive composition, meat quality parameters, and flavor precursors. The 2-month-old pigeon meat was selected as the optimal raw material due to its suitable protein content (23.39%), desirable meat texture, color, and significantly higher levels of amino acids (179.22 mg/100 g), which provided an ideal substrate basis for enzymatic hydrolysis. Then, the optimal raw material was treated with a variety of proteases (Neutral protease, Flavor protease, Acid protease, Alkaline protease, Trypsin, Papain) to prepare protease hydro lysates. Among protease hydro lysates, the flavor protease hydro lysate had a prominent umami taste, and its degree of hydrolysis (15.87%), sweet amino acids (0.61 mg/mL) and nucleotides (367.45 µg/mL) content were significantly higher than those of other samples except trypsin. Meanwhile, the content of small molecule peptides was significantly higher (94.42%). HS-SPME-GC-MS detected protease hydro lysates contained diverse volatile organic compounds (VOCs), among which the flavor protease hydro lysate contained significantly higher amounts of aldehydes (69.99%) and esters (8.98%) than other treatments, which had more meaty and fruity flavor. Consequently, flavor protease hydrolysis was identified as the most effective method for enhancing the taste and aroma of protease hydro lysates. This study provided an innovative strategy for the development of flavored pigeon meat products.

For a long time, milk fat has been recognized as a potential risk factor in the diet for cardiovascular disease because of its high saturated fatty acid content. However, mounting evidence may call into question this narrow-minded view, as it does not account for the complex and at times paradoxical relationship between dairy consumption and health. This review suggests that an integrative approach should be adopted to re-evaluate the health benefits of milk fat. We suggest that milk fat should not be viewed from a solely "saturated fat" perspective and should be considered a four-dimensional system: functional lipid diversity, food matrix structure, dose-response relationship, and individual metabolic characteristics. We first call attention to the fact that milk fat is not simplified in its fatty acid classifications and thus is molecularly heterogeneous. Second, we will discuss the modulation of lipid digestion kinetics and metabolic fate by the food matrix. Third, we combine epidemiological evidence, which shows the different kinds of nonlinear dose-response relationships between dairy consumption and health outcomes. Fourth, we discuss the contribution of genetic background, gut microbiota, and metabolic status to interindividual variability in response to milk fat. Finally, we discuss the implications of this framework for dietary guidelines, clinical practice, and innovation of dairy products. The change in paradigm from a single "saturated fat" to a multidimensional approach resolves inconsistencies that plagued the single "saturated fat" paradigm and offers a scientific playing field for personalized nutrition and precision dietary recommendations.

Minerals are indispensable for infant development, but their concentrations in human milk vary considerably among studies. This meta-analysis synthesized data from 60 studies comprising 8,376 samples to estimate the pooled concentrations of Ca, P, Mg, Fe, Zn, Cu, K, Na and Se. Although heterogeneity was substantial (I2 = 97.9–99.5%), no single study materially altered the estimates. The associations with lactation stage, geographical region and analytical method were tested by meta-regression with Šidák correction across 27 tests. After correction, lactation stage was associated with Zn (adjusted P < 0.0001, adjusted R2 = 30.73%) and Cu (adjusted P < 0.0001, adjusted R2 = 34.97%), geographical region with Ca (adjusted P = 0.0024, adjusted R2 = -5.72%), and analytical method with Fe (adjusted P < 0.0001, adjusted R2 = 39.75%). Nevertheless, heterogeneity remained extreme for every mineral, thus the estimates should therefore be interpreted as comparative summaries, not universal reference values.

Infant formula rice flour (IFRF) is a digestive-promoting formula containing yam, chicken gizzard lining, malt, and Hericium erinaceus (H. erinaceus), with banana, skim milk, and oligosaccharides to mask bitterness. Its potential role in juvenile functional dyspepsia (FD) via gut microbiota modulation was unexplored. This study investigated IFRF's anti-FD effect in an iodine acetamide-induced juvenile rat model. IFRF improved gastrointestinal dysfunction by enhancing motility, digestive enzyme activity, and balancing brain-gut peptides. Gut microbiota analysis showed IFRF increased alpha-diversity, raised sulfate-reducing and SCFA-producing bacteria (Desulfovibrio, Clostridium), and reduced FD marker bacteria (Prevotella, Akkermansia), significantly elevating fecal acetic, propionic, and butyric acid. Moreover, IFRF regulated the "Ghrelin-GOAT-GHSR-AGRP/alpha-MSHMC4R '' pathway to promote motility and appetite. Thus, IFRF ameliorates FD by normalizing gut microbiota, enhancing motility, and stimulating appetite, offering a safe therapeutic approach for juvenile FD.

Ganoderma lucidum (G. lucidum) spore oil is a premium functional lipid, but its safety is frequently compromised by phthalate plasticizers (PAEs). Although supercritical fluid extraction (SFE) is widely used to obtain spore oil, the co-extraction of these hazardous PAEs remains a critical bottleneck. This study introduces an integrated in situ adsorption strategy within the SFE process, coupling one-step micro-interfacial purification with an AHP-CRITIC multi-criteria decision model to mathematically optimize the inherent yield-quality trade-off. The application of activated carbon (AC) and activated clay (ACLT) revealed distinct physicochemical trade-offs. For AC, its non-selective microporous network caused massive competitive physical entrapment, depleting above 70

With the rapid development of the Camellia oleifera industry, tea saponin (TS), a bioactive component in C. oleifera seed meal, has garnered increasing attention in production and application research. This study innovatively employed ultrasound-assisted ethanol extraction combined with AB-8 macroporous resin purification (10% ethanol, 20 g/L TS, 8 BV loading volume, 8 h adsorption time) to effectively prepare high-purity (95.43 ± 0.04%) TS (HP-TS) with a relatively high yield (40.75 ± 0.52%) from C. oleifera seed meal. Furthermore, HP-TS alleviated hypertension-induced myocardial fibrosis in rats by inhibiting the protein expression of ACE, TGF-β1, Smad3, COL I, p65, p50, and pro-inflammatory factors in the ACE-AT1R/TGF/NF-κB pathways (p < 0.05). This study provides scientific evidence for the high-value utilization of tea seed meal and opens up possibilities for TS as an active ingredient in health foods and pharmaceuticals targeting antimyocardial fibrosis.

INTRODUCTION:Obesity-associated non-alcoholic fatty liver disease (NAFLD) remains a global health burden with limited treatment options. Human milk fat substitutes (HMFS), designed to mimic the triacylglycerol structure of breast milk, have shown potential metabolic benefits. However, the mechanisms underlying their effects on hepatic lipid metabolism remain unclear. OBJECTIVES:This study aims to evaluate the therapeutic effects of HMFS on established high fat diet-induced metabolic dysfunction and to delineate the lipid-mediated pathways involved. METHODS:A high-fat diet-induced obese mouse model was used to evaluate HMFS effects on metabolic parameters, liver histology, and lipid composition. Untargeted lipidomics identified candidate bioactive lipids. qPCR and Western blot were performed to assess hepatic gene and protein expression involved in lipid metabolism and signaling. Steatotic hepatocyte assays examined LPC 18:2 induced GPR119-AMPK activation. Molecular docking and molecular dynamics simulations were conducted to characterize LPC 18:2-GPR119 binding interactions. RESULTS:HMFS significantly reduced weight gain, hepatic triacylglycerols, and serum dyslipidemia, and improved liver enzyme profiles. Lipidomics revealed a marked elevation of LPC 18:2 alongside broad triacylglycerol reduction. HMFS upregulated enzymes involved in triacylglycerol hydrolysis and phospholipid remodeling, restoring hepatic GPR119-AMPK activation and promoting fatty acid oxidation over lipogenesis. Spearman correlation analysis revealed that LPC 18:2 levels were inversely correlated with obesity markers and positively correlated with GPR119-AMPK signaling. In vitro, LPC 18:2 replicated these effects in hepatocytes, reducing steatosis and enhancing AMPK phosphorylation. Computational analyses demonstrated stable LPC 18:2-GPR119 binding with favorable interaction energies. CONCLUSION:HMFS alleviates diet-induced metabolic impairments in mice by enriching LPC 18:2, which activates GPR119-AMPK signaling to promote hepatic lipid catabolism. These findings provide mechanistic evidence supporting structured lipids as potential nutritional interventions for obesity-related liver disease.