Search Results (91)

The oleaginous yeast Rhodotorula glutinis is a promising industrial host for the simultaneous production of lipids and carotenoids, yet the transcriptional regulation governing carbon flux toward these metabolites is poorly understood. As a foundational step, we performed a comparative transcriptomic analysis on bioreactor cultures under optimized fed-batch conditions with varying carbon-to-nitrogen (C/N) ratios and metal supplementation, comparing a nutrient-replete control (C) with conditions favoring high lipid (HLP) or high carotenoid (HCP) production. This study was designed as a preliminary, in-depth case study using single, well-controlled bioreactor runs per condition, with the goal of generating a comprehensive transcriptional map to identify key candidate genes for future validation. The data delineates two distinct presumptive metabolic strategies. The HLP regime was associated with broad transcriptional downregulation, channeling carbon toward lipogenesis via specific upregulation of the fatty acid synthase complex (FAS1/2, Log₂FC(HLP/HCP) > 2.99) and concerted suppression of β-oxidation genes (Log₂FC < −9.70). Conversely, the HCP condition was characterized by significant upregulation of NADPH-supplying pathways, including the pentose phosphate pathway (e.g., rpiA, Log₂FC(HCP/C) = 11.39) and an NADP⁺-dependent glyceraldehyde-3-phosphate dehydrogenase (gapN, Log₂FC(HCP/C) = 12.24). Notably, a putative beta-carotene hydroxylase (CrtZ) was uniquely sustained in the HCP condition (Log₂FC(HLP/HCP) = −10.65), strongly correlating with torularhodin accumulation and suggesting its novel role in torulene hydroxylation. This exploratory study reveals prospective transcriptional determinants of carbon partitioning in R. glutinis and provides a prioritized genetic blueprint for future hypothesis-driven research with full biological replication. Full article

Alcohol use disorder (AUD) predisposes individuals to pneumonia, acute respiratory distress syndrome, and chronic obstructive pulmonary disease, yet the mechanisms underlying alcohol-related lung disease (ARLD) remain unclear. Alveolar type II (AT2) epithelial cells play a central role in ethanol (EtOH) metabolism, surfactant production, alveolar repair, and pulmonary innate immunity. To examine EtOH-mediated effects, immortalized human AT2 cells were treated with 22–130 mM EtOH for 6 h (concentration-dependent) and 65 mM EtOH for 6–72 h (time-dependent). Cytotoxicity, inflammation, surfactant lipid/protein dysregulation, fatty acid ethyl ester (FAEE) formation, cellular stress responses, AMP-activated protein kinase (AMPKα) signaling, and mitochondrial function were analyzed. EtOH disrupted surfactant homeostasis by reducing dipalmitoylphosphatidylcholine and surfactant protein C (SP-C). Importantly, EtOH inactivated AMPKα, downregulated CPT1A (involved in β-oxidation of fatty acids), and upregulated lipogenic proteins ACC1 and FAS, accompanied by increased ER stress markers (GRP78, p-eIF2α, and CHOP). Expression of carboxyl ester lipase (FAEE-synthesizing enzyme) and FAEE levels increased with EtOH exposure, further exacerbating oxidative and ER stress, impairing mitochondrial energetics, ATP production, and AT2 cell function. These findings suggest that EtOH-induced FAEE formation, dysregulation of AMPKα-CPT1A signaling, and surfactant contribute to AT2 cell dysfunction and play a critical role in the pathogenesis of ARLD. Full article

Obesity and related metabolic disorders are closely linked to dysregulated lipid metabolism, where the metabolic balance of diacylglycerol (DAG) played a pivotal role. Although cis-palmitoleic acid (cPOA) exhibits anti-obesity effects, its efficacy varies across dietary conditions, and its molecular mechanisms remains unclear. In this study, we investigated the dose-dependent regulatory effects of cPOA on DAG metabolic shunting in db/db mice, employing lipidomics, pathway analysis, and gene/protein expression assays. Under a basal diet, low-dose cPOA (75 mg/kg) inhibited DAG-to-triglyceride (TAG) conversion, reducing hepatic lipid accumulation, while medium-to-high doses (150–300 mg/kg) redirected DAG flux toward phospholipid metabolism pathways (e.g., phosphatidylcholine [PC] and phosphatidylethanolamine [PE]), significantly lowering body weight and adiposity index. In high-fat diet (HFD)-fed mice, cPOA failed to reduce body weight but alleviated HFD-induced hepatic pathological damage by suppressing DAG-to-TAG conversion and remodeling phospholipid metabolism (e.g., inhibiting PE-to-PC conversion). Genetic and protein analyses revealed that cPOA downregulated lipogenic genes (SREBP-1c, SCD-1, FAS) and upregulated fatty acid β-oxidation enzymes (CPT1A, ACOX1), while dose-dependently modulating DGAT1, CHPT1, and PEMT expression to drive DAG metabolic shunting. Notably, DAG(36:3, 18:1–18:2) emerged as a potential biomarker for HFD-aggravated metabolic dysregulation. This study elucidated cPOA as a bidirectional regulator of lipid synthesis and oxidation, improving lipid homeostasis through dose-dependent DAG metabolic reprogramming. These findings provide novel insights and strategies for precision intervention in obesity and related metabolic diseases. Full article

Endometrial cancer (EC) is a complex gynecologic malignancy that requires a deeper understanding of its molecular basis to improve therapeutic strategies. In this study, we investigated the role of fatty acid (FA) reprogramming in the progression of EC. We analyzed FA profiles to identify the stage-specific changes and gene expression profiles of key enzymes involved in FA synthesis, desaturation, elongation, transport, and oxidation at different stages of EC. Our results show that EC tissues have lower levels of saturated FA and branched-chain FA, higher levels of very long-chain FA, n-3 polyunsaturated FA (PUFA), and monounsaturated FA, with the exception of myristoleic acid. The differences in n-6 PUFA were inconsistent. Gene expression analysis revealed the upregulation of key enzymes controlling de novo FA synthesis, including ACACA, FASN, SCD1, and ELOVL1. In contrast, the expression of genes related to FA transport in the cell and β-oxidation was downregulated. The expression of some genes related to PUFA metabolism was upregulated, while others were downregulated. These results demonstrate a reprogramming of lipid metabolism in EC tissues and suggest potential targets for novel therapeutic interventions in EC. Full article

This investigation evaluates the impact of the EOB on chicken growth performance, meat quality, and lipid metabolism. Two hundred and fifty-six one-day-old, white-feathered broilers were randomly allocated to four groups. Each group was subdivided into eight replicates, each with eight unsexed chicks, including the control group (CON), EOB₁₅₀, EOB₂₅₀, and EOB₃₅₀, with 0, 150, 250, and 350 mg/L of the EOB added to the drinking water, respectively. The expression levels of genes associated with antioxidants and lipid metabolism were analyzed using real-time polymerase chain reaction (RT-PCR). Additionally, the FA profile of the breast muscle was determined using gas chromatography. The data displayed that those birds in the EOB₂₅₀ group had a higher breast muscle index compared to the CON group. The breast meat in the EOB groups showed that there is increased yellowness, water holding capacity (WHC), and polyunsaturated fatty acids (PUFAs), while cooking losses, drip losses, and saturated fatty acids (SFAs) were reduced compared to the CON. The application of supplements for the EOB₂₅₀ and EOB₃₅₀ groups increased antioxidant indices as well as the expression of antioxidant-related genes in the liver and muscles. However, these groups decreased the concentrations of triglycerides (TG), total cholesterol (TC), and low-density lipoprotein (LDL-C) in serum and liver compared to the EOB₁₅₀ and CON groups. These EOB groups downregulated expression of some genes linked to liver FA synthesis and elevated the expressions of lipid β-oxidation-related genes compared to the CON. It can be concluded that the supplementation with 250 mg/L of the EOB has the potential as an alternative water additive in the broiler industry. Full article

Obstructive nephropathy (ON), characterized by urine flow disruption, can induce chronic kidney disease (CKD). Although the release of the obstruction is performed as the primary intervention, renal pathology often persists and progresses. Accordingly, the murine model of releasing unilateral ureteral obstruction (RUUO) is valuable for investigating the molecular events underlying renal damage after obstruction release. Remarkably, after RUUO, disturbances such as oxidative stress, inflammation, lipid accumulation, and fibrosis continue to increase. Mitochondrial dysfunction contributes to fibrosis in the UUO model, but its role in RUUO remains unclear. Additionally, the impact of using antioxidants to restore mitochondrial function and prevent renal fibrosis in RUUO has not been determined. This study aimed to determine the therapeutic effect of pre-administering the antioxidant sulforaphane (SFN) in the RUUO model. SFN was administered 1 day before RUUO to evaluate mitochondrial biogenesis, fatty acids (FA) metabolism, bioenergetics, dynamics, and mitophagy/autophagy mechanisms in the kidney. Our data demonstrated that SFN enhanced mitochondrial biogenesis and reestablished mitochondrial oxygen consumption and β-oxidation. These effects collectively reduced lipid accumulation and normalized mitochondrial dynamics, mitophagy, and autophagy, thereby mitigating fibrosis after obstruction. Our findings suggest that SFN holds promise as a potential therapeutic agent in ON-induced CKD progression in RUUO and opens new avenues in studying antioxidant molecules to treat this disease. Full article

In this work, the hypolipidemic and antioxidative capacity of FSGLR (S7) and GIEWA (S10) from miiuy croaker swim bladders was explored systematically in an oleic acid (OA)-induced nonalcoholic fatty liver disease (NAFLD) model of HepG2 cells. Moreover, the hypolipidemic activity of S7 and S10 and their antioxidative abilities were preliminarily investigated in combination with molecular docking technology. The results indicated that S7 and S10 could decrease the amount of lipid accumulation and the content of triglycerides (TG) and total cholesterol (TC) in the OA-induced NAFLD cell model in a dose-dependent manner. In addition, S7 and S10 exhibited better bile salt binding, pancreatic lipase (PL) inhibition, and cholesterol esterase (CE) inhibition capacities. The hypolipidemic mechanisms of S7 and S10 were connected with the downregulation of the mRNA expression levels of adipogenic factors, including sterol-regulatory element-binding protein-1c (SREBP-1c), acetyl-CoA carboxylase (ACC), sterol-regulatory element-binding protein (SREBP)-2, hydroxymethylglutaryl-CoA reductase (HMGR), and fatty acid synthase (FAS) (p < 0.01), and the upregulation of the mRNA expression of β-oxidation-related factors, including carnitine palmitoyltransferase 1 (CPT-1), acyl-CoA oxidase 1 (ACOX-1), and peroxisome proliferator-activated receptor α (PPARα). Moreover, FSGLR (S7) and GIEWA (S10) could significantly protect HepG2 cells against OA-induced oxidative damage, and their antioxidant mechanisms were related to the increased activity of intracellular antioxidant proteases (superoxide dismutase, SOD; glutathione peroxidase, GSH-PX; catalase, CAT) to remove excess reactive oxygen species (ROS) and decrease the production of malondialdehyde (MDA). The presented findings indicate that the hypolipidemic and antioxidant functions and mechanisms of S7 and S10 could make them potential hypolipidemic and antioxidant candidates for the treatment of NAFLD. Full article

Background/Objectives: The backfat thickness of pigs is closely related to dorsal subcutaneous fat deposition and meat quality, and appropriate reduction in backfat thickness is important for improving pork quality. The present study investigated the effect of acorn diet on the backfat thickness and lipase activity of Yuxi black pigs and to gain further insight into the molecular mechanism of the acorn diet on the dorsal subcutaneous fat deposition of Yuxi black pigs by transcriptome sequencing (RNA-seq). Methods: Thirty-six Yuxi black pigs with an initial body weight of 99.60 ± 2.32 kg (three replicates per group and six pigs per replicate) were randomly divided into two groups (CON group was fed a basic diet and AEG group was fed 30% acorn diets). Pigs were individually fed twice daily and had access to water ad libitum throughout the experiment. The test period was 4 months. Results: Results showed that backfat thickness and ACC, MDH, and LPL lipase activities were significantly reduced in the AEG group than in the CON group (p < 0.05). In addition, RNA-seq identified 826 differentially expressed genes (DEGs), with 505 up-regulated and 321 down-regulated. The DEGs were significantly enriched in the lipid metabolism process and lipid catabolic process, fatty acid (FA) catabolic process, and FA β-oxidation according to GO enrichment analysis. LEP, CHPT1, UCP3, ACOX1, SCD5, and ACAA1 were screened as key differential genes regulating dorsal subcutaneous fat deposition. Conclusions: The above results indicated that feeding the 30% acorn diet could regulate the expression of genes involved in fat deposition and reduce lipase activity, thereby decreasing the backfat thickness, inhibiting the deposition of dorsal subcutaneous fat, and improving the pork quality. The findings of this experiment established a basis for subsequent research into the molecular mechanisms underlying the impact of acorn diets on fat deposition in Yuxi black pigs and provided the scientific evidence to promote the exploitation and industrialization of acorns. Full article

Iron overload is a common complication in various chronic liver diseases, including non-alcoholic fatty liver disease (NAFLD). Lipid and bile acid metabolism disorders are regarded as crucial hallmarks of NAFLD. However, effects of iron accumulation on lipid and bile acid metabolism are not well understood. Ferulic acid (FA) can chelate iron and regulate lipid and bile acid metabolism, but its potential to alleviate lipid and bile acid metabolism disorders caused by iron overload remains unclear. Here, in vitro experiments, iron overload induced oxidative stress, apoptosis, genomic instability, and lipid deposition in AML12 cells. FA reduced lipid and bile acid synthesis while increasing fatty acid β-oxidation and bile acid export, as indicated by increased mRNA expression of PPARα, Acox1, Adipoq, Bsep, and Shp, and decreased mRNA expression of Fasn, Acc, and Cyp7a1. In vivo experiments, FA mitigated liver injury in mice caused by iron overload, as indicated by reduced AST and ALT activities, and decreased iron levels in both serum and liver. RNA-seq results showed that differentially expressed genes were enriched in biological processes related to lipid metabolism, lipid biosynthesis, lipid storage, and transport. Furthermore, FA decreased cholesterol and bile acid contents, downregulated lipogenesis protein FASN, and bile acid synthesis protein CYP7A1. In conclusion, FA can protect the liver from lipid and bile acid metabolism disorders caused by iron overload by targeting FASN and CYP7A1. Consequently, FA, as a dietary supplement, can potentially prevent and treat chronic liver diseases related to iron overload by regulating lipid and bile acid metabolism. Full article

The metabolism of glucose and lipids plays a crucial role in the normal homeostasis of the body. Although glucose is the main energy substrate, in its absence, lipid metabolism becomes the primary source of energy. The main means of fatty acid oxidation (FAO) takes place in the mitochondrial matrix through β-oxidation. Glioblastoma (GBM) is the most common form of primary malignant brain tumor (45.6%), with an incidence of 3.1 per 100,000. The metabolic changes found in GBM cells and in the surrounding microenvironment are associated with proliferation, migration, and resistance to treatment. Tumor cells show a remodeling of metabolism with the use of glycolysis at the expense of oxidative phosphorylation (OXPHOS), known as the Warburg effect. Specialized fatty acids (FAs) transporters such as FAT, FABP, or FATP from the tumor microenvironment are overexpressed in GBM and contribute to the absorption and storage of an increased amount of lipids that will provide sufficient energy used for tumor growth and invasion. This review provides an overview of the key enzymes, transporters, and main regulatory pathways of FAs and ketone bodies (KBs) in normal versus GBM cells, highlighting the need to develop new therapeutic strategies to improve treatment efficacy in patients with GBM. Full article

(1) Background: In aquaculture, chronic stress due to high stocking density impairs animals’ welfare and results in declined fishery production with low protein quality. However, most previous studies evaluated the effects of high stocking density on trout in freshwater rather than seawater. (2) Methods: Juvenile trout were reared for 84 days in circular tanks under three stocking densities, including low density (“LD”, 9.15 kg/m³), moderate density (“MD”, 13.65 kg/m³), and high density (“HD”, 27.31 kg/m³) in seawater. The final densities of LD, MD, and HD were 22.00, 32.05 and 52.24 kg/m³, respectively. Growth performance and lipid metabolism were evaluated. (3) Results: Growth performance and feeding efficiency were significantly reduced due to chronic stress under high density in mariculture. The digestive activity of lipids was promoted in the gut of HD fish, while the concentration of triglycerides was decreased in the blood. Furthermore, decreased acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS), increased hormone-sensitive lipase (HSL) concentrations, and activated hepatic β-oxidation processes were observed in trout under HD. Redundancy analysis showed that glycerol and HSL can be used as potential markers to evaluate the growth performance of trout in mariculture. (4) Conclusions: We showed that chronic high stocking density led to negative effects on growth performance, reduced de novo synthesis of fatty acids, and enhanced lipolysis. Full article

Kidney transplantation offers a longer life expectancy and a better quality of life than dialysis to patients with end-stage kidney disease. Ischemia–reperfusion injury (IRI) is thought to be a cornerstone in delayed or reduced graft function and increases the risk of rejection by triggering the immunogenicity of the organ. IRI is an unavoidable event that happens when the blood supply is temporarily reduced and then restored to an organ. IRI is the result of several biological pathways, such as transcriptional reprogramming, apoptosis and necrosis, innate and adaptive immune responses, and endothelial dysfunction. Tubular cells mostly depend on fatty acid (FA) β-oxidation for energy production since more ATP molecules are yielded per substrate molecule than glucose oxidation. Upon ischemia–reperfusion damage, the innate and adaptive immune system activates to achieve tissue clearance and repair. Several cells, cytokines, enzymes, receptors, and ligands are known to take part in these events. The complement cascade might start even before organ procurement in deceased donors. However, additional experimental and clinical data are required to better understand the pathogenic events that take place during this complex process. Full article

The present study investigated potential bioactive natural products from the EtOH extract of Salix chaenomeloides twigs using column chromatography, leading to the isolation of six compounds (1–6), which were characterized as two proanthocyanidins, procyanidin B₂ (1) and procyanidin B₁ (2), and four phenolic compounds, 4-hydroxybenzoic acid β-D-glucosyl ester (3), di-O-methylcrenatin (4), p-coumaric acid glucoside (5), and syringin (6) by the comparison of their NMR spectra with the reported data and high-resolution (HR)-electrospray ionization mass spectroscopy (ESI-MS) analysis. We investigated the potential of six compounds (1–6) to inhibit adipogenesis in 3T3-L1 preadipocytes, which showed that the compounds (1–6) significantly reduced lipid accumulation in 3T3-L1 adipocytes without affecting cell proliferation. Notably, compound 1 demonstrated a remarkable 60% and 90% reduction in lipid levels with 50 and 100 µM treatments, respectively. Oil Red O staining results indicated that compound 1 significantly inhibits the formation of lipid droplets, comparable to the effect of T863, an inhibitor of triglyceride used as a positive control, in adipocytes. Compound 1 had no effect on the regulators PPARγ, C/EBPα, and SREBF1 of adipocyte differentiation in 3T3-L1 preadipocytes, but compound 1 activated the fatty acid oxidation regulator, PPARα, compared to the lipogenic-induced control. It also suppressed fatty acid synthesis by downregulating the expression of fatty acid synthase (FAS). Finally, compound 1 induced the mRNA and protein levels of CPT1A, an initial marker of mitochondrial fatty acid oxidation in 3T3-L1. This finding substantiates the anti-lipogenic and lipolytic effects of procyanidin B₂ (1) in 3T3-L1 preadipocytes, emphasizing its pivotal role in modulating obesity-related markers. Full article

Hyperlipidemia, characterized by elevated serum lipid concentrations resulting from lipid metabolism dysfunction, represents a prevalent global health concern. Ginsenoside Rb1, compound K (CK), and 20(S)-protopanaxadiol (PPD), bioactive constituents derived from Panax ginseng, have shown promise in mitigating lipid metabolism disorders. However, the comparative efficacy and underlying mechanisms of these compounds in hyperlipidemia prevention remain inadequately explored. This study investigates the impact of ginsenoside Rb1, CK, and PPD supplementation on hyperlipidemia in rats induced by a high-fat diet. Our findings demonstrate that ginsenoside Rb1 significantly decreased body weight and body weight gain, ameliorated hepatic steatosis, and improved dyslipidemia in HFD-fed rats, outperforming CK and PPD. Moreover, ginsenoside Rb1, CK, and PPD distinctly modified gut microbiota composition and function. Ginsenoside Rb1 increased the relative abundance of Blautia and Eubacterium, while PPD elevated Akkermansia levels. Both CK and PPD increased Prevotella and Bacteroides, whereas Clostridium-sensu-stricto and Lactobacillus were reduced following treatment with all three compounds. Notably, only ginsenoside Rb1 enhanced lipid metabolism by modulating the PPARγ/ACC/FAS signaling pathway and promoting fatty acid β-oxidation. Additionally, all three ginsenosides markedly improved bile acid enterohepatic circulation via the FXR/CYP7A1 pathway, reducing hepatic and serum total bile acids and modulating bile acid pool composition by decreasing primary/unconjugated bile acids (CA, CDCA, and β-MCA) and increasing conjugated bile acids (TCDCA, GCDCA, GDCA, and TUDCA), correlated with gut microbiota changes. In conclusion, our results suggest that ginsenoside Rb1, CK, and PPD supplementation offer promising prebiotic interventions for managing HFD-induced hyperlipidemia in rats, with ginsenoside Rb1 demonstrating superior efficacy. Full article

Our previous study established that chrysoeriol (CHE) can reduce reactive oxygen species (ROS) accumulation, apoptosis, and autophagy in vitro culture (IVC) of porcine embryos. However, the role of CHE in oocyte maturation and lipid homeostasis is unclear. Herein, we aimed to elucidate the effect of CHE on porcine oocyte competence in vitro maturation (IVM) and subsequent embryo development. The study chooses parthenogenetic activated porcine oocytes as the research model. The study revealed that the cumulus expansion index and related gene expressions are significantly elevated after supplementing 1 μM CHE. Although there were no significant differences in nuclear maturation and cleavage rates, the blastocyst formation rate and total cell numbers were significantly increased in the 1 μM CHE group. In addition, CHE improved the expression of genes related to oocyte and embryo development. ROS was significantly downregulated in all CHE treatment groups, and intracellular GSH (glutathione) was significantly upregulated in 0.01, 0.1, and 1 μM CHE groups. The immunofluorescence results indicated that mitochondrial membrane potential (MMP) and lipid droplet (LD), fatty acid (FA), ATP, and functional mitochondria contents significantly increased with 1 μM CHE compared to the control. Furthermore, CHE increased the expression of genes related to lipid metabolism, mitochondrial biogenesis, and β-oxidation. Full article