Search Results (435)

1,3-Dioleoyl-2-palmitoylglycerol (OPO) mimics breast milk fat, yet its regulation of gut short-chain fatty acids (SCFAs) remains unclear. Herein, stable OPO microcapsules (94.12% efficiency) were prepared using soy protein isolate/maltodextrin. Integrating metabolomics and transcriptomics in mice, we found OPO intervention dose-dependently increased acetic, propanoic, and butyric acids in the jejunum and colon. Multi-omics analysis revealed OPO upregulated key genes governing lipid digestion (FABP2, NPC1L1, MTTP) and bile secretion (ABCA1). These results indicate that OPO is closely associated with increased SCFA production, suggesting a potential pathway wherein optimized host nutrient digestion and absorption patterns create a favorable metabolic environment for distal microbial fermentation, rather than merely providing substrates. This study provides correlative multi-omics insights into a potential mechanism for OPO’s health benefits in functional foods. Full article

Blood lipid responses to diet vary substantially between individuals, limiting the effectiveness of uniform dietary recommendations, and genetic variation may contribute to this heterogeneity through gene–diet interactions. This systematic review and meta-analysis evaluated nutrigenetic interactions affecting blood lipid traits. Web of Science Core Collection and MEDLINE were searched in April 2026 to identify human studies testing interactions between dietary exposures—including macronutrient composition, fat quantity, fat type [polyunsaturated fatty acids (PUFA), monounsaturated fatty acids (MUFA), and saturated fatty acids (SFA)], carbohydrate, and protein—and lipid-related genes. Interaction p-values were synthesized using a weighted Stouffer’s Z method with Benjamini–Hochberg false discovery rate correction. Twenty studies (n = 20), comprising approximately 9800 participants, met the inclusion criteria. The most consistent evidence was observed for CETP, APOE, and APOB, particularly in relation to broader macronutrient composition and fat-related exposures, while ABCA1 and APOA5 showed significant but more limited evidence. PUFA was the most consistent specific dietary exposure. In contrast, ABCG5, ABCG8, and CYP7A1 lacked sufficient data for meta-analysis, highlighting major gaps in the current literature. Overall, the findings support the view that lipid responses to diet are partly genotype-dependent, while also underscoring the need for larger, better harmonized studies to clarify and extend the current evidence base. Full article

Cu and Cd, as common heavy metals occurring in the oceans, can induce oxidative stress and toxic responses in marine organisms. Important economic cephalopods inhabit the eastern coastal areas of China, and exposure to Cu and Cd poses a threat to their normal physiological activities, resulting in serious inhibition of their growth. However, the underlying toxicological mechanisms affecting these cephalopods’ larval stages remain to be elucidated. Here, indicators of oxidative stress and transcriptomics were employed to analyze the toxicological mechanisms of S. esculenta larvae exposed to Cd and Cu. GO and KEGG analysis results indicated that material transport, cellular processes, DNA replication, and other processes were inhibited. A comprehensive analysis of a protein–protein interaction network and KEGG pathways was used to explore the mechanism underlying the toxicity of co-exposure to Cu and Cd toward S. esculenta larvae. We found that Cu and Cd induce significant damage and oxidative stress. The results showed that among 20 identified key genes, ITGA4, LAMA1, and LAMC1, which are involved in the adhesion and connection between cells and the extracellular matrix; COL6A1, COL6A3, COL6A4, and COL6A6, which maintain the integrity of the extracellular matrix; and ABCA1, ABCC5, and ABCC7, which regulate the transmembrane transport of Cu and Cd were involved in the mechanism of toxicity. We suggest that co-exposure to the metals primarily inhibits the connection and adhesion between the cells of the larvae and disrupts the structure and function of the extracellular matrix. The results provide a foundation for understanding the toxicological mechanism of S. esculenta and should be of benefit to artificial breeding programs. Full article

The rice stem borer (RSB), Chilo suppressalis, is one of the most destructive rice pests in China and chlorantraniliprole has been extensively used for its control over the past decade. However, the continuous and intensive application of chlorantraniliprole has accelerated the development of resistant RSB populations in field, thereby threatening sustainable rice production. In this study, a field resistant strain of RSB exhibited a 181.76-fold resistance level to chlorantraniliprole compared to a susceptible strain. To explore the potential involvement of ATP-binding cassette (ABC) transporters in chlorantraniliprole resistance, four candidate ABC transporter genes (CsABCC1, CsABCC3, CsABCA3 and CsABCD2) were analyzed in resistant and susceptible strains. Compared to the susceptible strain, the expressional levels of CsABCC1 and CsABCC3 were significantly upregulated by 1.58- and 1.38-fold, respectively, whereas of CsABCA3 and CsABCD2 showed non-significant differences in the resistant strain. RNA interference assays demonstrated that naked dsRNA induced only limited gene silencing, while chitosan-mediated dsRNA delivery significantly improved RNAi efficiency. Following feeding with chitosan-coated dsCsABCC1 and dsCsABCC3, the expression levels of both genes were reduced by 44.63% and 38.49%, respectively, relative to the control and the larval mortality increased following chlorantraniliprole treatment to 63.33% and 56.67%, respectively. In addition, silencing CsABCC1 caused a greater reduction in larval weight after insecticide treatment. These findings indicated that CsABCC1 and CsABCC3 are involved in chlorantraniliprole detoxification and may contribute to resistance. Overall, this study provides evidence for the functional involvement of ABC transporters in chlorantraniliprole resistance and highlights chitosan-mediated RNAi as a promising complementary approach for resistance management within integrated pest management programs. Full article

Intestinal dysfunction and parenteral nutrition (PN) can trigger a spectrum of liver disorders collectively referred to as intestinal failure-associated liver disease (IFALD), for which therapeutic options remain limited. In the present study, we investigated the modulatory effects of the bioactive xanthophyll carotenoid lutein in an in vitro IFALD model utilizing human THLE-2 hepatocytes exposed to lipopolysaccharide and Intralipid to mimic PN–associated inflammatory and metabolic stress. Because lutein is poorly water-soluble and patients receiving PN lack enteral intake of this compound, we also evaluated the cyto- and hemocompatibility of a human serum albumin–based lutein nanoformulation developed to enable intravenous administration. A bead-based multiplex immunoassay revealed that lutein attenuated dysregulation of inflammatory and metabolic signaling by modulating total and phosphorylated levels of MAPKs, NF-κB, Akt, STAT5, CREB, and p70S6K. Lutein also affected lipid metabolism–related gene expression, decreasing SREBF2 and restoring ABCA1 and PRKAA2 mRNA toward control levels, as determined by qPCR. Nanoformulated lutein, with a mean particle size of approximately 160 nm, was non-toxic in THLE-2 cells and exhibited hemocompatibility in a human erythrocyte hemolysis assay. Together, our findings provide both biological and technological rationale for further exploration of lutein-based strategies to mitigate IFALD in patients receiving PN. Full article

Phospholipid transfer protein (PLTP) is a lipid transfer protein classically studied in the context of plasma lipoprotein metabolism, high-density lipoprotein (HDL) remodeling, and cardiovascular disease risk. PLTP facilitates phospholipid transfer between lipoproteins and regulates HDL particle size and composition through interactions with apolipoprotein A-I and apolipoprotein A-II. While its systemic roles in cholesterol handling, reverse cholesterol transport, and inflammatory signaling are well established, the cell-autonomous functions of PLTP within cardiomyocytes remain poorly defined, particularly in human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs). Extensive experimental and clinical studies demonstrate that PLTP enhances ABCA1-dependent cholesterol efflux primarily by stabilizing ABCA1 at the plasma membrane and by promoting the generation of lipid-poor apolipoprotein A-I and pre-β HDL particles, which serve as efficient cholesterol acceptors; the magnitude of these effects depends on cellular context, PLTP expression levels, and the availability of lipid acceptors. PLTP expression is metabolically regulated and widely distributed across tissues, including macrophages and other non-hepatic cells, supporting roles beyond circulating lipoprotein remodeling. Altered PLTP activity has been linked to atherosclerosis, cardiovascular disease, and inflammatory pathways, underscoring its relevance to cardiac pathophysiology. Emerging evidence further suggests that intracellular cholesterol distribution, rather than total cholesterol content alone, critically influences mitochondrial membrane composition, bioenergetics, and stress signaling in cardiomyocytes. These observations raise the possibility that PLTP-regulated lipid flux may indirectly shape mitochondrial function by modulating cellular cholesterol homeostasis. This review synthesizes current knowledge of PLTP biology, cholesterol metabolism, and lipoprotein remodeling, and integrates these concepts with emerging frameworks in cardiomyocyte lipid metabolism and mitochondrial physiology. We highlight human iPSC-derived cardiomyocytes as a strategic and translationally relevant platform to investigate PLTP’s non-canonical, cell-intrinsic roles, identify critical knowledge gaps, and propose future directions for elucidating how PLTP may influence mitochondrial function in human cardiac cells. Full article

Under the deformation potential model, the superconducting phenomenon in ABC-stacked multilayer graphene under a vertical electric field is investigated using linear combination operators and unitary transformation methods. Through the deformation potential model applied to a linear continuous medium, the effect of the external electric field is converted into the deformation potential energy of the crystal. Deformation potential phonons (LA phonons) act as propagators, generating electron–electron interactions. As the electric field increases, the ratio of the electric displacement vector to the dielectric function ($D/\epsilon$) rises, leading to an increase in the electron ground-state energy, the opening of the band gap, and an enhancement of the attractive electron–electron interaction. With further increases in the external electric field, the deformation potential constant of the crystal ($D_l$) increases. When the phonon vibration frequency ($\omega$) is around 8.5 THz, and the conditions are satisfied—where the wave vectors of different LA phonons are equal in magnitude and opposite in direction, and the electron spins are opposite—the attractive electron–electron interaction reaches its maximum ($H_{eff}$), resulting in the emergence of superconductivity. Our study also provides a new perspective for understanding the unique quantum properties—such as strong correlations, superconductivity, and ferromagnetism—in different stacking configurations like AB, ABC, and ABCA. Full article

Alzheimer’s disease (AD) is the most prevalent form of dementia and is characterized by abnormal aggregation of β-amyloid (Aβ) peptides, tau proteins, and neuroinflammation in the central nervous system (CNS). While most AD research has focused on the brain, the molecular pathology of the spinal cord remains poorly understood. In this study, we investigated amyloid pathology, neurodegeneration, neuroinflammation, and cholesterol metabolism across distinct regions of the spinal cord and examined sex-specific differences using a model of AD, 5xFAD mice. Our data reveal that Aβ accumulation was restricted to the cervical spinal cord at 3 months but was evident in all areas of the spinal cord by 9 months, with similar patterns in both female and male animals. Despite this early and progressive Aβ deposition, no significant neuronal loss was observed in the ventral horn of the cervical spinal cord in either sex at 3 or 9 months of age. In contrast, there was a significant positive correlation between Aβ deposition and Iba1+ cell density in the spinal cord of 5xFAD mice. The number of Iba1+ cells in both the grey and white matter was significantly increased in female and male 5xFAD mice compared with age-matched wild-type (WT) littermates at 9 months of age. Astrocytic responses, however, were sex-specific: female, but not male, 5xFAD mice exhibited a significant increase in GFAP+ astrocytes in the grey matter of the thoracic and lumber spinal cord at 9 months compared with 3 months and relative to age-matched WT controls in the cervical and thoracic spinal cord. Furthermore, GFAP+ area in the thoracic spinal cord was significantly higher in female 9-month-old 5xFAD mice compared with their male counterparts, indicating a female-specific astrocytic response in AD spinal cord pathology. Our data also show an increase in free cholesterol (Filipin+ area) in 5xFAD mice at 9 months relative to WT controls, accompanied by altered expression of cholesterol metabolism genes, including downregulation of Abca1, Cyp46a1 and Cyp27a1. Collectively, these findings provide new insights into AD progression in the spinal cord, highlighting molecular pathology of AD extending beyond the brain. Full article

Background/Objectives: Chitooligosaccharide (COS) is a marine-derived natural product obtained from shrimp and crab shells. Although its anti-inflammatory and antioxidant activities are documented, its potential effects on obesity and metabolic syndrome remain largely unclear. This study aimed to investigate the efficacy of COST (MW ≈ 1000 Da) against high-fat diet (HFD)-induced obesity and metabolic syndrome in Bama pigs. Methods: Bama pigs were fed a HFD for 12 weeks to establish an obesity model, followed by 12 weeks of oral COST administration. Serum biochemical parameters, tissue indicators, histopathology, and gene/protein expression related to cholesterol metabolism were analyzed. Fecal bile acid (BA) profiles, gut microbiota composition, and short-chain fatty acid (SCFA) levels were also examined. Results: COST treatment significantly attenuated weight gain and improved multiple components of metabolic syndrome, including insulin resistance, dyslipidemia, and inflammation. Mechanistically, COST upregulated intestinal ABCG5/ABCG8 to promote cholesterol excretion, increased ABCA1 expression in intestine and liver to enhance reverse cholesterol transport (RCT), and upregulated hepatic LDL-R to facilitate LDL-C clearance from circulation while modulating hepatic cholesterol synthesis via SREBP2 downregulation and RNF145 upregulation. These transcriptional changes were confirmed at the protein level for LXR, LDL-R, and ABCA1. Additionally, COST decreased fecal secondary BA levels, reshaped gut microbiota composition, and increased SCFA production, with significant correlations among these factors. Conclusions: COST ameliorates protective effects against HFD-induced obesity and metabolic syndrome, potentially through the regulation of cholesterol metabolism and the modulation of the gut microbiota-BA-SCFA network. Full article

Cadmium (Cd) is a major environmental pollutant due to its high mobility and persistence in soils, facilitating entry into the food chain and threatening ecosystems and human health. However, the mechanisms that enable Salix species, well adapted for Cd remediation, to both tolerate and accumulate Cd remain elusive. Here, two Salix genotypes with contrasting Cd tolerance were examined under control and Cd stress using integrated physiological, transcriptomic, and metabolomic analyses of roots and leaves. The Cd-tolerant genotype (Salix suchowensis P294) maintained biomass under Cd stress, whereas the Cd-sensitive genotype (Salix sinopurpurea × Salix integra P646) showed a ~17% reduction. P294 accumulated more Cd in its stems (132.76 mg kg⁻¹) and leaves (122.25 mg kg⁻¹) than P646 (93.54 and 56.24 mg kg⁻¹). Transcriptomics responses were stronger in roots, with 896 DEGs in P294 and 462 in P646, enriched in nitrogen metabolism, phenylpropanoid biosynthesis, and metal transport, whereas only 167 and 176 DEGs were detected in leaves for P294 and P646, respectively. Metabolomics revealed more altered metabolites in roots (125 in P294, 89 in P646), mainly organic acids, amino acids, and flavonoids, compared with leaves (46 and 66). RT-qPCR validated the root-specific upregulation of key detoxification and transport genes (ABCA7, PRX72, GSTU1, GSTU4, ZIP1). These results reveal a root-centered regulatory network underlying Cd accumulation and tolerance, integrating detoxification, redox homeostasis, and structural reinforcement, as well as providing valuable targets for genetic improvement of phytoremediation efficiency. Full article

A549 cells are widely used as an in vitro model of alveolar type II (ATII) epithelial cells; however, their phenotype and metabolic state are highly sensitive to culture conditions, cell density, and the duration of static, non-passaged cultivation. Here, we examined how prolonged static culture affects lipid metabolism, mitochondrial bioenergetics, and viability in A549 cells. A549 cultures were maintained without passaging for up to 25 days in DMEM or Ham’s F-12 and analyzed using lipid secretion assays, targeted lipidomics, [¹⁴C]-acetate incorporation, Seahorse bioenergetic profiling, and transcriptional analysis of stress-associated markers. Several surfactant-associated readouts were highest during early culture, peaking on day 7, as evidenced by elevated expression of ABCA3 and SP-A and maximal secretion of surfactant-associated phospholipids. With prolonged cultivation and increasing culture density, cellular phosphatidylglycerol levels declined progressively and became nearly undetectable by day 25, accompanied by reduced anabolic lipid metabolism, lower oxygen consumption, and impaired glycolytic activity. These changes coincided with increased reactive oxygen species, elevated intracellular Ca²⁺ levels, and increased expression of stress-associated transcripts, including CASP1, IL1B, and C3. Later stages were also associated with reduced mitochondrial respiration and decreased viability. Collectively, our findings show that prolonged static culture is associated with metabolic remodeling and reduced bioenergetic capacity in A549 cells. Full article

Bcakground: Hepatocellular carcinoma (HCC) is a prevalent malignancy with limited therapeutic options. Drug repurposing offers an attractive strategy to accelerate anticancer discovery. The pleuromutilin class of antibiotics, including the human-approved agent lefamulin and the veterinary drug tiamulin, has shown preliminary anticancer potential, but its efficacy and mechanism in HCC remain unexplored. Methods: The anti-tumor effects of lefamulin and tiamulin were evaluated in HCC cell lines, patient-derived organoids, and a C57BL/6 mouse subcutaneous tumor model. Safety was assessed in a human normal hepatocyte cell line and by histopathological examination of major organs in treated mice. Mechanistic investigations were performed using RNA-sequencing, RT-qPCR, immunohistochemistry (IHC), filipin staining, pharmacological rescue assays, and shRNA-mediated gene silencing. Results: In this study, we found that both lefamulin and tiamulin markedly inhibited HCC cell proliferation in vitro and significantly suppressed tumor growth in vivo (lefamulin vs. control, p = 0.014; tiamulin vs. control, p = 0.021), without causing significant toxicity. RNA-sequencing analysis revealed consistent downregulation of the cholesterol transporter Abca1 (ATP-binding cassette transporter A1) and alterations in cell adhesion molecule pathways. Functional studies confirmed that treatment reduced ABCA1 protein levels, leading to intracellular cholesterol accumulation and aberrant distribution. Furthermore, treated tumors exhibited a significant increase in CD8⁺ T-cell infiltration, with CD4⁺ T cells and macrophage infiltration remained unchanged, indicating a specific modulation of the tumor immune microenvironment. Conclusions: These findings suggest that lefamulin and tiamulin are promising therapeutic candidates for HCC. Full article

Background/Objectives: Mexicans are disproportionately affected by dyslipidemia, specifically low high-density lipoprotein (HDL-C) and high triglyceride (TG) concentrations. Research on the genetic contributions to dyslipidemia, conducted primarily among European populations, has identified numerous single-nucleotide polymorphisms (SNPs) with small effect sizes and low replication rates. A genetic risk score (GRS) can examine the cumulative effects of multiple SNPs and potentially explain greater phenotypic variability than individual SNPs. GRS in Mexican populations and those without diagnosed dyslipidemia are limited. This study aims to construct a GRS from lipid metabolism-related SNPs and determine its associations with blood lipid concentrations in young Mexican college students. Methods: Adults (ages 18–25 years, n = 580) provided a fasting blood sample to determine TG and HDL-C concentrations. DNA was genotyped for 14 SNPs in lipid metabolism pathways (reverse cholesterol transport [RCT], cellular lipid uptake, and lipoprotein formation and transport). Additive (number of risk alleles) and weighted (regression-derived β coefficients) GRS were calculated for individual pathways, and their sum (total GRS) was explored. Associations among individual SNPs, GRS, and blood lipids were determined through general linear models in SAS. Results: The additive RCT and total GRS were associated with TG (both p < 0.05). The RCT pathway explained 3.4% of the variability in TG concentrations, and the total GRS explained 6.1%. The weighted RCT GRS was associated with HDL-C (p = 0.007). The ATP-binding cassette protein (ABCA1) rs9282541 variant was most strongly associated with HDL-C (p = 0.016). When this SNP was removed from the GRS, the association became non-significant. Conclusions: SNPs in lipoprotein metabolism pathways cumulatively associate with blood lipid concentrations in young Mexican adults. The ABCA1-rs9282541 variant, previously shown to be positively associated with low HDL-C concentrations in Amerindian populations, had the strongest association with HDL-C. Further work is needed to elucidate the roles of genetic admixture and lifestyle risk factors in dyslipidemia in this population. Full article

ABC transporters (ATP-binding cassette transporters) constitute one of the largest known protein families and are widely distributed in plants. Their primary function involves utilizing energy derived from ATP hydrolysis to transport substrates across membranes against concentration gradients. These transporters play crucial roles in the translocation and accumulation of metabolites, stress tolerance, disease resistance, and plant defense. Lotus is an important traditional Chinese medicinal herb and contains active ingredients primarily composed of secondary metabolites, whose transport and accumulation require the involvement of ABC transporters. However, the function of these ABC transporters remains unexplored in lotus. In this study, 122 ABC transporter genes were predicted within the lotus genome. We identified 1~15 conserved motifs among the NnABC proteins and most of them were stable proteins predominantly located on the plasma membrane with ExPASy-ProtParam, ProComp and WoLF PSORT analysis. Phylogenetic tree analysis revealed that the lotus ABC transporter gene family could be divided into eight subfamilies, from ABCA to ABCI, and the evolution was predominantly driven by purifying selection. Comparative transcriptome analysis between the cultivar ‘Yindu Zhimi’ with orange-reddish stamen and ‘Weishan Hong’ with yellowish stamen, along with quantitative real-time PCR results, showed that the NnABCG25 gene is highly specifically expressed in the orange-reddish stamen. Molecular docking demonstrated that NnABCG25 has a stable affinity for lycopene, β-carotene and β-apocarotenal, suggesting its potential involvement in the transport of carotenoids in the stamen. These findings expand our understanding of the role of ABC transporters in the transport and accumulation of carotenoids, as well as providing a valuable reference for research on the ABC transporter gene family in other plants. Full article

Fat deposition plays a crucial role in regulating the production performance and meat quality of broilers. Although the heterogeneity of mammalian adipocytes has been extensively studied, research on the molecular mechanisms underlying differences in lipid droplet accumulation in avian adipocytes remains limited. This study confirmed a significant positive correlation (R² > 0.81, p < 0.001) between the SSC signal and lipid droplet content via fluorescence staining of lipid droplets, Oil Red O staining, and triglyceride (TG) quantification. Based on this, a label-free sorting strategy using SSC signals was established to sort differentiated chicken preadipocytes, obtaining high lipid droplet (H) and low lipid droplet (L) subpopulations, which were subsequently subjected to transcriptome sequencing and differential gene expression (DEG) analysis, followed by GO and KEGG enrichment analysis. The results indicated no significant differences in the expression of adipogenesis marker genes (PPARG, LPL, CD36, PLIN1, PLIN2) between the high lipid droplet (H) and low lipid droplet (L) groups, suggesting that both groups are at similar stages of differentiation. KEGG analysis revealed that both the H vs. NC and L vs. NC comparisons were enriched in common pathways, including the PPAR signaling pathway, ECM–receptor interaction, focal adhesion, cytokine–receptor interaction, and calcium–Apelin signaling pathway, suggesting that both groups of cells had activated the adipogenesis program. GO analysis showed that, in both H vs. NC and L vs. NC comparisons, differentially expressed genes (DEGs) were enriched in biological processes (BPs) related to cell adhesion, nucleosome assembly, chromatin remodeling, and receptor activity, as well as cellular components (CCs) such as the extracellular matrix, cytoskeleton, and nucleosome organization, indicating extensive gene reprogramming and activation of signaling transduction during differentiation. In the H vs. L comparison, enriched pathways included ABC transporters, ECM–receptor interaction, focal adhesion, gap junctions, microtubule-related processes, and neuroactive ligand–receptor interactions, involving lipid transmembrane transport, cytoskeleton stabilization, and signal transduction regulation, suggesting that high lipid droplet cells are more mature in lipid droplet transport, storage, and homeostasis maintenance. GO enrichment results further supported this conclusion, as H vs. L specifically enriched processes related to microtubule-related processes, cell cycle, and redox reactions (BPs), as well as chromosome organization, cytoskeleton, and motor activity (CC/MF), indicating that high lipid droplet cells maintain lipid droplet fusion and metabolic homeostasis via enhanced microtubule transport and antioxidant regulation. Differential gene analysis revealed that the L group upregulated genes associated with fatty acid synthesis and elongation (ACACA, FASN, SCD, FADS2, ELOVL1), cholesterol and isoprenoid biosynthesis (HMGCR, SQLE, MSMO1, DHCR7, DHCR24, FDPS, LSS), and fatty acid oxidation (PPARA, PPARD, ACAD11, SIRT5), reflecting a metabolic characteristic of concurrent lipid synthesis and mobilization; the H group, conversely, upregulated genes associated with lipid droplet formation and storage (G0S2, MOGAT1, GPAT4, PLIN4, AUP1), lipid transport (ABCA1, ABCA2, ABCG1, OSBPL3, VLDLR), and antioxidant defense (GPX3, GPX4, HMOX1), exhibiting a storage and homeostasis-oriented metabolic state. In the NC, L, and H groups, the expression of five genes—GEM, SPP1, ABCA1, PDLIM3, and ITGA8—showed a gradual increase, suggesting that these genes were associated with preadipocyte differentiation and lipid droplet deposition. In summary, although the high and low lipid droplet subpopulations of chicken preadipocytes exhibit similar differentiation states, they form distinct metabolic orientations. The L group is characterized by active lipid synthesis, fatty acid oxidation, and membrane lipid remodeling, while the H group predominantly features lipid droplet storage, lipid transport, and antioxidant homeostasis. This study highlights the molecular mechanisms underlying the metabolic heterogeneity of avian adipocytes and provides a theoretical basis for poultry fat deposition regulation and genetic improvement. Full article