Search Results (167)

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

Background: Obstructive sleep apnea (OSA) syndrome is a common sleep-related breathing disorder characterized by recurrent upper airway collapse during sleep and is closely associated with metabolic dysregulation, including insulin resistance, adipose tissue dysfunction, and impaired lipid metabolism. Perilipin-2 (PLIN-2), a lipid droplet-associated protein involved in triglyceride storage and regulation of lipolysis, may reflect alterations in lipid homeostasis associated with OSA. Objective: This study aimed to evaluate the association between serum PLIN-2 levels and OSA and to assess the relationship between PLIN-2 concentrations and disease severity. Methods: A total of 231 participants were included in this study, comprising 70 healthy controls and 161 patients with OSA. Patients were classified according to apnea–hypopnea index (AHI) as having mild (n = 60), moderate (n = 52), or severe OSA (n = 49). All participants underwent overnight polysomnography (PSG). Results: Serum PLIN-2 levels were significantly higher in patients with OSA and increased progressively with disease severity. PLIN-2 levels were positively correlated with polysomnographic indices of OSA severity, including AHI and oxygen desaturation index. ROC analysis demonstrated good discriminative performance of PLIN-2 for OSA presence and for distinguishing mild from severe OSA. Conclusions: This study is the first to demonstrate an association between serum PLIN-2 levels and OSA. Our findings suggest that PLIN-2 may serve as a novel biomarker reflecting metabolic and lipid-related disturbances in OSA and may provide new insights into the pathophysiological link between intermittent hypoxia and altered lipid metabolism. Full article

Background/Objectives: Bone marrow adipose tissue (BMAT) serves multiple physiological roles but accumulates with age, compromising skeletal health. This expansion is largely driven by an adipogenic drift of bone marrow mesenchymal stromal cells (BMSCs), shifting attention toward stromal cell fate regulation as a target to preserve bone marrow homeostasis. Preventing adipogenic commitment may be as relevant as directly inducing osteogenesis for maintaining a bone-permissive marrow microenvironment. Here, we investigated whether olive leaf extract (OLE) and its purified secoiridoid components, oleacin (OC) and oleuropein aglycone (OA), modulate the adipogenic differentiation and proliferative capacity of human BMSCs. Methods: Human BMSCs were induced to undergo adipogenic differentiation and treated with OLE, OC, or OA. Intracellular lipid accumulation and the expression of key adipogenic regulators were assessed. Proliferative capacity was evaluated under both maintenance and adipogenic conditions. Results: Under adipogenic conditions, OLE markedly reduced intracellular lipid accumulation and induced a coordinated downregulation of PPARγ, PLIN1, FABP4, ADIPOQ, LEP and the adipogenesis-associated miR-422a. In contrast, OC and OA exerted more selective and specific effects on biomarkers, indicating the partial and complementary modulation of adipogenic programs. Notably, OLE also increased BMSC proliferation under both maintenance and adipogenic conditions, suggesting the preservation of a less committed stromal cell pool. Although the relative contribution of enhanced proliferation versus the direct inhibition of adipogenic pathways cannot be fully disentangled, the combined molecular and functional data support a dual action of OLE on stromal cell fate. Conclusions: OLE limits adipogenic commitment while maintaining stromal cell proliferative competence, processes that are critically involved in BMAT expansion and bone marrow dysfunction. OC and OA contribute to OLE bioactivity deserving further investigation, particularly in combination, as potential modulators of BMAT expansion. Full article

Familial partial lipodystrophy type 3 (FPLD3) is a rare autosomal dominant disorder caused by mutations in peroxisome proliferator-activated receptor gamma(PPARG), which encodes the key adipogenic transcription factor peroxisome proliferator-activated receptor gamma(PPARγ). Clinical diagnosis is challenging due to phenotypic overlap with common metabolic syndromes. We identified a novel PPARG variant in a Chinese family and performed comprehensive functional characterization to elucidate its pathogenic mechanism. The proband, a 15-year-old boy presenting with atypical fat distribution, severe insulin resistance, hypertriglyceridemia, and pancreatitis, underwent clinical evaluation and whole-exome sequencing. The identified variant was confirmed by Sanger sequencing. Its functional impact was assessed through in silico modeling, luciferase reporter assays, protein stability analysis (cycloheximide chase), and evaluation of mitochondrial function (JC-1 staining) and adipocyte gene expression in cellular models. A heterozygous PPARG c.634C>T (p.Arg212Trp, R212W) variant was identified and segregated with the phenotype. Functional studies revealed that the R212W mutant exhibits a partial loss of transcriptional activity (~40% of wild-type) while retaining ligand sensitivity. Crucially, we demonstrated that the mutant protein has significantly reduced stability due to accelerated degradation. In adipocyte models, R212W expression led to impaired mitochondrial membrane potential, depleted cellular ATP levels, and downregulated expression of key metabolic genes (glucose transporter 4[GLUT4], adiponectin[ADIPOQ], fatty acid binding protein 4[FABP4], lipoprotein lipase[LPL], perilipin 1[PLIN1]). These functional deficits were partially rescued by treatment with the PPARγ agonist rosiglitazone. We report a novel pathogenic PPARG R212W variant associated with FPLD3. Our data extend beyond a simple loss-of-function model by establishing a multi-faceted pathogenic mechanism involving protein destabilization, mitochondrial dysfunction, and cellular bioenergetic failure. The partial rescue by rosiglitazone suggests a potential therapeutic avenue. This study underscores the importance of integrating clinical phenotyping with deep functional analysis to diagnose and understand rare monogenic lipodystrophies. Full article

Cancer is a multifactorial disease influenced not only by genetic and epigenetic alterations but also by interactions with the surrounding microenvironment. Among the hallmarks of cancer, metabolic reprogramming enables tumor cells to adapt and survive under adverse conditions. These metabolic alterations also induce changes in stromal cells. In clear cell renal cell carcinoma (ccRCC), adipocytes are among the most abundant stromal components. We have previously shown that ccRCC progression depends on the bidirectional crosstalk between tumor epithelial cells and neighboring adipocytes. Here, we investigated the effects of ccRCC on naïve human adipose tissue (hRAN). Human retroperitoneal adipose tissue fragments from two distinct donors (n = 2) were incubated with conditioned media (CMs) derived from ccRCC tumors (T-CM) or renal epithelial cells (Tc-CM). We analyzed the expression of adipocytokines, differentiation and browning markers, metabolic parameters, and steroid hormone receptor profiles. The exposure of hRAN to T-CM or Tc-CM led to significant alterations in the expression of adiponectin and leptin, as well as markers associated with differentiation and browning, including PLIN1, HSL, PGC1α, PPARγ, and UCP1. Adipocytes from treated hRAN were smaller than those from controls, suggesting dedifferentiation. Moreover, expression of FABP4 and MCT1 was significantly increased in explants treated with T-CM compared to control media. Conditioned media from these treated hRAN samples showed elevated lactate secretion, indicating enhanced lactatogenesis. Given the role of sex hormones in metabolic regulation, we examined the expression of estrogen (ER), androgen (AR), and progesterone (PR) receptors. While AR and PR levels remained unchanged, both ERα and ERβ were significantly upregulated after T-CM treatment. Metabolic reprogramming in renal tumors induces profound adaptive changes in adjacent adipose tissue. The dedifferentiation and browning of adipocytes, altered adipocytokine expression, and increased lactate production observed in hRAN reflect the metabolic stress imposed by the tumor environment. Here, we provide evidence, using an ex vivo model, of a dynamic partnership between human adipose tissue and ccRCC tumors. Full article

Sheep’s meat production and quality are influenced by genetic and physiological factors that affect muscle development, growth, and fat deposition metabolism. However, the breed-specific transcriptional landscapes driving these traits in Indian sheep breeds, especially in Nellore (meat-type) and Deccani (wool-meat type) breeds are remain unexplored. Therefore, this study aimed to investigate the differences in muscle growth and fat deposition between Nellore and Deccani breeds by integrating transcriptomic profiling, carcass characteristics, and histological analysis of longissimus dorsi muscle and liver tissues. Carcass assessment revealed higher Hot Carcass Weight (HCW), Cold Carcass Weight (CCW), Hot Carcass Yield (HCY) and Cold Carcass Yield (CCY), and larger myofibrillar cross-sectional area (p < 0.05), indicating enhanced musculature, which was observed in Nellore. Deccani showed elevated Intramuscular Fat (IMF) deposition (p < 0.05), indicating improved meat flavour/juiciness. Transcriptomic profiling revealed several Differentially Expressed Genes (DEGs) associated with meat quality and quantity traits. In Nellore, the genes WFIKKN2, FGFRL1, FKBP4, and IRF1 were upregulated, while the gene TAS1R2 was downregulated, leading to enhanced muscle development, superior carcass traits, thermotolerance, and immunity. While Deccani showed higher expression of lipid metabolism genes PLA2G4F, ACSL1, ACOX1, CPT1A, and PLIN1, which are linked to higher IMF content. Functional enrichment analysis revealed 46 significantly enriched GO terms for the DEGs (p < 0.05), including oxidoreductase activity, muscle development, etc. These outcomes demonstrate novel genetic markers and key biological insights into the regulation of muscle development, thermotolerance, immunity, and IMF for future validation in Indian sheep breeds. Full article

Cardiovascular disease is the leading cause of mortality in insulin-resistant individuals, with metabolic cardiomyopathy preceding overt heart failure in a substantial proportion of patients with diabetes. Skeletal muscle accounts for approximately 40% of body mass and nearly 80% of insulin-stimulated glucose disposal, positioning it as a major determinant of systemic lipid flux. Dysregulation of lipid droplet dynamics, lipolysis, and fatty acid trafficking in skeletal muscle alters circulating lipid availability and promotes ectopic lipid deposition and mitochondrial stress in the myocardium. Intramyocellular lipid handling is governed by coordinated actions of lipid droplets, perilipin proteins (PLIN2 and PLIN3), adipose triglyceride lipase (ATGL), and diacylglycerol acyltransferases (DGAT1/2), which together regulate the rate and composition of fatty acid release into the circulation. Impaired coupling between intramyocellular lipid droplet turnover and mitochondrial oxidation in insulin-resistant muscle increases circulating free fatty acids, reducing cardiac oxidative capacity. In response, the myocardium undergoes mitochondrial lipid remodeling, including alterations in cardiolipin composition that impair cristae structure and electron transport chain efficiency. Excess lipid exposure activates apoptosis signal-regulating kinase-1 (ASK-1), promoting cardiomyocyte apoptosis and inflammatory signaling, while peroxisome proliferator-activated receptor gamma (PPARγ) modulates lipid uptake, storage, and mitochondrial oxidation in a context-dependent manner. This review integrates skeletal muscle–cardiac lipid crosstalk with ASK-1 and PPARγ signaling to define mechanisms linking peripheral insulin resistance to early myocardial dysfunction and to identify targets for intervention before irreversible cardiac remodeling develops. Full article

Background: MYC dysregulation is frequent in ocular adnexal sebaceous carcinoma (SebCA), an aggressive malignancy without precision therapy. Fatty acid synthase (FASN) expression and lipid metabolism are commonly perturbed in high-MYC-expressing tumors; however, the role of MYC and FASN in the coregulation of lipid biosynthesis and tumorigenesis in SebCA is unknown. Methods: The aim of this study was to characterize the effects of FASN inhibition on MYC expression, oncogenic processes, and lipid profiles in vitro, using non-neoplastic human Meibomian gland epithelial cells (HMGECs) and three primary SebCA cell lines, and in vivo, utilizing a conditionally MYC-overexpressing mouse model. Results: FASN inhibition reduced cell viability, proliferation, and clonogenicity and altered the saturation profile of fatty acids across multiple lipid classes. The relative saturation of ceramides was the most variable between treatment conditions. MYC overexpression in the murine Meibomian gland promoted proliferation while suppressing sebaceous differentiation. Subsequent topical FASN inhibition further reduced sebaceous differentiation, attenuated PLIN2 expression, and induced apoptotic cell death. Conclusions: Collectively, these findings suggest that MYC expression in SebCA is responsive to FASN inhibition. Pharmacologic targeting of FASN reveals a metabolic vulnerability that may serve as a target for future therapeutic development. Full article

Background/Objectives: Long-chain fatty acids induce lipid droplet formation in several cell types including cancer cells. These lipid droplets have been shown to accumulate in various cancers and are dysregulated in many pathologies. Thus, this study was designed to examine the many unique long-chain fatty acids and their abilities to induce lipid droplet formation in cancer cells. Methods: HeLa human cervical cancer cells were incubated with individual fatty acids and live-stained for lipid droplets. This study analyzed four saturated, four monounsaturated, and nine polyunsaturated (4 omega-3, 4 omega-6, and 1 omega-9) fatty acids. This diversity of fatty acids was chosen to highlight any important non-uniform differences in the regulation of lipid droplet formation by unsaturated fatty acids. The area of the lipid droplets and the number of lipid droplets per cell were measured and compared between the different fatty acid conditions. Results: Unsaturated fatty acids induced lipid droplets differently compared to saturated fatty acids. Further, an inverse relationship was established between average area of lipid droplets and the average number of lipid droplets per cell. Finally, two perilipin genes (PLIN1/2) involved in lipid droplet formation were shown to have significantly higher expression with the two polyunsaturated fatty acids (alpha- and gamma-linolenic acid) versus the saturated fatty acid (stearic acid) condition. Conclusions: Together, different fatty acids produce structurally different lipid droplets. It will be important to further investigate the biochemistry and mechanistic differences in the formation of these lipid droplets under these specific long-chain fatty acid conditions. Full article

Background/Objectives: Non-alcoholic fatty liver disease (NAFLD), also referred to as metabolic dysfunction-associated fatty liver disease (MAFLD), is the most common chronic liver disease, closely associated with obesity and Metabolic Syndrome (MetS). Perilipin-2 (PLIN2), the most abundant lipid droplet protein in the liver, is linked to lipid accumulation and inflammation, the hallmarks of NAFLD. The role of PLIN2 in NAFLD etiopathogenesis remains partially understood. This study aims to elucidate the relationship between serum PLIN2 levels and other disease-related parameters in NAFLD, investigate the role of PLIN2 in disease pathogenesis, and evaluate its utility as a biomarker in NAFLD diagnosis. Methods: The study included 46 patients diagnosed with NAFLD who presented internal medicine outpatient clinics and 44 healthy controls. Results: Serum PLIN2 level was found to be statistically significantly higher in the NAFLD patient group compared to the control group. In the NAFLD group, a statistically significant positive correlation was detected between PLIN2 and Body Mass Index (BMI), hip circumference, C-reactive protein (CRP), and platelet count. In ROC analysis, taking the cut-off value for serum PLIN2 level as 5.52 ng/mL predicted the diagnosis of NAFLD with 50% sensitivity and 97.7% specificity. Conclusions: PLIN2 determination demonstrated high specificity at the proposed cut-off value and may represent a promising complementary biomarker for NAFLD, particularly when interpreted alongside other clinical and laboratory parameters. Circulating PLIN2 appears to be influenced by metabolic and inflammatory parameters. Full article

Background/Objectives: Obesity, a metabolic disorder resulting from an energy imbalance, often leads to excess fat and related diseases. Browning of white adipose tissue, which increases energy expenditure, is a promising anti-obesity strategy. Herbal medicines are considered safer than conventional drugs, but their fat browning mechanisms remain unclear. Therefore, this study aims to examine the effects of Coix lacryma-jobi L. and Raphanus sativus L., alongside their active compounds, coixol and sinigrin. Methods: Cytotoxicity in 3T3-L1 cells was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Lipid accumulation was quantified by the Oil Red O (ORO) staining. Immunofluorescence staining was employed to evaluate mitochondrial activity and uncoupling protein 1 (UCP1). Protein and mRNA expressions were analysed using western blot and quantitative real-time polymerase chain reaction (qRT-PCR), respectively. Results: In 3T3-L1 adipocytes, ORO staining showed reduced lipid accumulation and droplet size after treatment. qRT-PCR, western blot, and immunostaining revealed that coixol and sinigrin upregulated browning markers (UCP1, PGC-1α, PRDM16) and beige fat genes (Cd137, Cidea, Cited, Fgf21, Tbx1, Tmem26). They also upregulated mitochondrial biogenesis genes (Cox4, Nrf1, Tfam), downregulated lipogenic genes (Fasn, Lpl, Srebf1, Acaca), and increased lipolytic (Atgl, Hsl, Plin1) and fatty acid oxidation genes (Aco1, Cpt1, Ppara). Mechanistic studies revealed that fat browning was associated with β3-adrenergic receptor activation and AMPK phosphorylation. Conclusions: Overall, coixol and sinigrin promote fat browning and metabolic improvement, highlighting their potential as natural anti-obesity agents. Full article

Abdominal fat deposition is an important economic trait in poultry, as excessive accumulation reduces feed efficiency and carcass yield. The gut microbiota is known to influence host energy metabolism and fat storage, suggesting its potential involvement in fat deposition. This study examined the relationship between intestinal microbiota and abdominal fat deposition in an F₂ population derived from Cherry Valley Ducks (♂) × Runzhou Crested White Ducks (♀) at 42 days of age. Based on abdominal fat rate, ducks with values of 0–0.75% and 1.5–2.25% were defined as the low (LF) and high (HF) abdominal fat groups, respectively. A combined multi-omics approach was used, including 16S rRNA gene sequencing, metagenomics, and whole transcriptomics, to compare high and low abdominal fat rate groups. 16S rRNA gene sequencing results showed that the cecum had the highest microbial diversity among all intestinal segments (duodenum, jejunum, ileum, and rectum) and was significantly enriched in carbohydrate metabolism pathways, highlighting its key role in nutrient utilization and growth. Therefore, the cecum was selected for further analysis. Metagenomic analysis of the cecum contents revealed significantly different intestinal microbial β diversity between the high and low abdominal fat rate groups (p < 0.05). The low abdominal fat rate group was enriched in beneficial microorganisms such as Paenibacillus, Butyrivibrio, Coprococcus, Ruminococcaceae, Veillonellaceae (Clostridiales), and Firmicutes. Conversely, the high abdominal fat rate group was characterized by an increased abundance of Bacteroidetes, including both beneficial and potentially pathogenic taxa such as Alistipes and Eggerthellales. The integrated analysis of metagenomic and whole transcriptome sequencing showed that Firmicutes and Bacteroidetes were not only related to energy metabolism, lipid metabolism, and amino acid metabolism, but also to the expression of FGF2, FKBP5, PNPLA2, PLIN3, FGFR2, DGAT2, and ACER2. In addition, Firmicutes and Bacteroidetes were also associated with 7 lncRNAs: XR_003493494.1, XR_003492471.1, XR_001190174.3, TCONS_00005095, XR_001190238.3, TCONS_00005095, and XR_003492841.1. In conclusion, this study highlights that the cecal microbiota is closely associated with abdominal fat deposition in ducks, elucidating its potential influence on host metabolism and gene expression. These findings enhance our understanding of the gut microbiota’s relationship with obesity and offer new strategies to modulate gut–microbe interactions to reduce abdominal fat accumulation in poultry. Full article

Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is highly prevalent worldwide and represents a growing healthcare challenge due to its risk of progression and association with metabolic comorbidities. Extracellular vesicles (EVs), nanosized membrane-bound particles mediating intercellular communication, have emerged as candidate biomarkers in multiple diseases. This study aimed to characterize serum EV profiles in MASLD patients, stratified into obese and lean groups using a body mass index cutoff of 23 for Asians. Methods: We enrolled 170 MASLD patients, 83 obese (median age 50, range 20–80) and 87 lean (median age 50, range 20–87), along with 57 non-MASLD controls (median age 44, range 21–86). Serum EV concentrations and particle sizes were quantified using nanoparticle tracking analysis and correlated with clinical and laboratory parameters. EV cargo proteins, including tetraspanins (CD9, CD63) and lipid droplet-associated perilipins (PLIN2, PLIN3), were assessed by Western blotting. Results: Obese MASLD patients displayed marked biochemical abnormalities, whereas lean MASLD patients showed levels comparable to non-MASLD controls. Nevertheless, serum EV concentrations were elevated in both the obese and lean MASLD groups. Importantly, in lean MASLD, EV levels correlated strongly with disruptions in lipid and glycemic homeostasis. Furthermore, a reduction in the PLIN3/CD63 ratio was observed in EVs isolated from lean MASLD patients. Conclusions: Circulating EVs are elevated in both obese and lean MASLD, but lean patients demonstrate a distinctive decrease in the EV PLIN3/CD63 ratio. These findings highlight the potential of EV profiling to uncover disease heterogeneity and to inform risk stratification in MASLD. Full article

Lipid droplets (LDs) are emerging as key regulators of metabolism and inflammation, with their buildup in microglia linked to aging and neurodegeneration. Perilipin-2 (Plin2) is a ubiquitously expressed LD-associated protein that stabilizes lipid stores; in peripheral tissues, its upregulation promotes lipid retention, inflammation, and metabolic dysfunction. Yet, its role in microglia remains unclear. Using CRISPR-engineered Plin2 knockout (KO) BV2 microglia, we examined how Plin2 contributes to lipid accumulation, bioenergetics, and immune function. Compared to wild-type (WT) cells, Plin2 KO microglia showed markedly reduced LD burden under basal and oleic acid-loaded conditions. Functionally, this was linked to enhanced phagocytosis of zymosan particles, even after lipid loading, indicating improved clearance capacity. Transcriptomics revealed genotype-specific responses to amyloid-β (Aβ), especially in mitochondrial metabolism pathways. Seahorse assays confirmed a distinct bioenergetic profile in KO cells, with reduced basal respiration and glycolysis but preserved mitochondrial capacity, increased spare reserve, and a blunted glycolytic response to Aβ. Together, these findings establish Plin2 as a regulator of microglial lipid storage and metabolic state, with its loss reducing lipid buildup, enhancing phagocytosis, and altering Aβ-induced metabolic reprogramming. Targeting Plin2 may represent a strategy to reprogram microglial metabolism and function in aging and neurodegeneration. Full article

Intramuscular fat (IMF) content is an important factor of goat meat quality, which is related to the proliferation and differentiation of intramuscular preadipocytes. Perilipin 5 (PLIN5) is a lipid droplet-associated protein; however, the specific function and underlying mechanism of PLIN5 in goat IMF deposition are still unclear. In this study, overexpression of PLIN5 significantly enhanced apoptosis and reduced the proliferation of preadipocytes and also promoted cellular lipid deposition via both the upregulation of the expression of peroxisome proliferator-activated receptor gamma (PPARγ) and a significant increase in the expression of lipogenesis-related genes. The inhibition of PLIN5 then confirmed these results. Untargeted lipidomics sequencing identified a total of 34 differentially expressed lipids after PLIN5 overexpression in goat preadipocytes and analysis by KEGG pathway enrichment, which are mainly involved in the PI3K-AKT signaling pathway. The lipid omics findings also show that ceramides and lysophosphatidylinositol were significantly upregulated, e.g., Cer (d35:1), Cer (d18:2/22:1), LPI (18:0), and LPI (16:0), after overexpression of the PLIN5 gene. Higher expression of LPI (16:0) or LPI (18:0) may regulate lipid droplet accumulation by activating PPARγ. Rescue experiments with the PI3K-AKT inhibitor (LY294002) and the PPARγ inhibitor (GW9662) showed that the PI3K-AKT signaling pathway is involved in the regulation of cell proliferation, and PPARγ is involved in the regulation of lipid deposition. In conclusion, our findings demonstrate that PLIN5 regulates lipid reconstitution in goat intramuscular fat via PPARγ and PI3K-AKT signaling pathways. This regulation delivered theoretical support for improving meat quality from the aspect of IMF deposition. Full article