Search Results (753)

To enhance the nutritional value of sheep fat, high-melting-point solid fat (HSO) and low-melting-point liquid oil (LSO) were prepared from Altay sheep rump fat via solvent fractionation. The effects of HSO and LSO on lipid metabolism and intestinal health were evaluated in a mouse model. Results showed that HSO, rich in saturated fatty acids (SFA), induced obesity, dyslipidemia, and colonic inflammation in mice. These adverse effects were associated with the upregulation of hepatic lipid synthesis genes such as Sterol regulatory element-binding protein 1c (SREBP-1c) and Fatty acid synthase (FAS), as well as increased expression of pro-inflammatory cytokines including Tumor necrosis factor-alpha (TNF-α) and Interleukin-6 (IL-6) in the colon. In contrast, LSO, which was predominantly composed of unsaturated fatty acids (UFA), did not cause significant metabolic disorders. Instead, it promoted the upregulation of fatty acid oxidation-related genes such as Peroxisome proliferator-activated receptor alpha (PPARα) and Acyl-CoA oxidase 1 (Acox1), helped maintain intestinal microbial balance, and enhanced the production of beneficial short-chain fatty acids (SCFAs), particularly butyrate and propionate. In conclusion, solvent fractionation effectively modulates the fatty acid composition of sheep fat, thereby influencing lipid metabolism and inflammatory responses through the regulation of key gene expression and modulation of the gut microenvironment. Full article

Dysregulated lipid metabolism is associated with cardiovascular disease, obesity and type 2 diabetes. In the current report, we explore the functional interactions between two important regulators of lipid metabolism, sterol regulatory element-binding protein 1 and 2 (SREBP1/2), and PRDI-BF1 and RIZ homology domain containing 16 (PRDM16). The SREBP family of transcription factors regulate cholesterol and fatty acid synthesis and metabolism, primarily in liver but also in white adipose tissue. PRDM16 is a major regulator of brown adipose tissue (BAT) biogenesis and function as well as an inhibitor of white adipogenesis. We find that PRDM16 interacts with the nuclear forms of SREBP1/2 and inhibits their transcriptional activities. Consequently, inactivation of PRDM16 enhances the expression of well-established SREBP target genes involved in fatty acid and cholesterol synthesis/metabolism. Importantly, PRDM16 inactivation increases the expression of LDL receptor mRNA (1.6-fold) and protein (1.7-fold) and augments the cellular uptake of LDL particles (2.3-fold). Supporting these findings, PRDM16-deficient cells accumulate more neutral lipids in a SREBP1/2-dependent manner. Inactivation of PRDM16 in white and brown preadipocyte cell lines and human adipose-derived stem cells enhances the expression of SREBP target genes. In addition, the expression of adipogenic markers was increased in mature white adipocytes generated from PRDM16-knockdown preadipocytes (1.8- to 3.9-fold). Thus, our study identifies PRDM16 as a novel inhibitor of SREBP-dependent lipid metabolism with implications for adipose biology and metabolic disease. Full article

Dairy cows experiencing negative energy balance (NEB) are prone to metabolic and inflammatory disorders, including ketosis, fatty liver, mastitis, endometritis, and hypocalcemia, which impair productive and reproductive performance. NEB elevates non-esterified fatty acids (NEFA) and β-hydroxybutyrate (BHBA), leading to disrupted lipid metabolism characterized by increased fatty acid synthesis (via SREBP-1c, ACC, FASN), impaired lipid export (downregulated MTTP, ApoB100, ACAT2), and reduced oxidation (suppressed SIRT1–PPARα–CPT1A/2 pathway), resulting in triacylglycerol (TAG) accumulation and ketosis. Excess reactive oxygen species (ROS) trigger oxidative and endoplasmic reticulum (ER) stress and apoptosis through JNK, p53/Nrf2, and PERK–eIF2α signaling, while HIF-2α–mediated hypoxia aggravates hepatic damage. Elevated NEFA/BHBA impair polymorphonuclear neutrophil (PMN) chemotaxis and phagocytosis, promoting mastitis and endometritis, and hypocalcemia further weakens immune defense. Rumen-protected choline (RPC) improves lipid metabolism by enhancing VLDL assembly and TAG export (upregulating MTTP, ApoB100, ATG3; inhibiting SREBF1, DGAT2), stimulating fatty acid oxidation (activating AMPK–PPARα–CPT1α), and reducing oxidative stress (suppressing ROS–ERN1). Moreover, RPC decreases IL-6 and TNF-α levels and enhances antioxidant capacity and PMN function. Overall, RPC alleviates NEB-induced metabolic and inflammatory diseases, supporting its inclusion in periparturient management to mitigate NEB and associated disorders. Full article

2,2′,4,4′-tetrabromodiphenyl ether (BDE-47) is a common environmental contaminant and widely detected in aquatic surroundings, while only a few reports exist on the hazard mechanism in economic aquatic animals. It has been shown that 40 and 4000 ng/g of BDE-47 dietary exposure over 42 days significantly increased the levels of blood triglycerides, glucose, and liver glycogen in carp (Cyprinus carpio). Tissue observations showed that BDE-47 resulted in vacuolation, atrophy, and fat deposition in hepatocytes. Combined metabolomic and transcriptomic analyses revealed that BDE-47 affected the inflammatory response and the biosynthesis of steroid hormones. This was further confirmed by gene expression related to inflammatory factors (il-10, tnf-α, il-1β, and tgf-β1), lipid metabolism (acc, fas, srebp, rxr, atgl, hsl, and lpl), and the steroid hormone biosynthetic pathway (11bhsd, hsd3b, and star). Thus, BDE-47 affects liver inflammatory response and lipid deposition through steroid hormone biosynthesis in carp. This helps us to understand how BDE-47 dietary exposure impacts inflammation and lipid metabolism in fish, which affects the health of aquaculture and has potential risks to human health. Full article

Influenza viruses are adept at hijacking host cellular machinery to facilitate their replication and propagation. A critical aspect of this hijacking involves the reprogramming of host cell metabolism. This review summarizes current findings on how influenza virus infection alters major metabolic pathways, including enhanced glycolysis, suppression of oxidative phosphorylation, diversion of TCA cycle intermediates for biosynthesis, and upregulation of lipid and amino acid metabolism. Key nutrients like glucose, glutamine, and serine are redirected to support viral RNA synthesis, protein production, and membrane formation. Moreover, these metabolic changes also modulate host immune responses, potentially aiding in immune evasion. We highlight the role of transcription factors such as SREBPs in lipid synthesis and the impact of one-carbon metabolism on epigenetic regulation. Finally, we discuss how targeting virus-induced metabolic shifts, using agents like 2-deoxyglucose or fatty acid synthesis inhibitors, offers promising avenues for antiviral intervention, while emphasizing the need for selective approaches to minimize harm to normal cells. Full article

Increased hepatic triacylglycerol (TG) storage in lipid droplets (LDs) is a hallmark of metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH). Human carboxylesterase 1 (CES1) regulates TG storage and secretion in hepatocytes, but the mechanism remains to be elucidated. We performed studies in rat hepatoma McArdle RH7777 cells stably transfected with CES1 cDNA and in Ces1d-deficient mice using a variety of biochemical, pharmacological and cell biology approaches including the assessment of gene expression, confocal immunofluorescence microscopy, lipid synthesis measurements and quantitative mass spectrometry. CES1-expressing cells accrued more TG compared to cells lacking CES1 when incubated with oleic acid. CES1 increased the expression of Srebf1c, Nr1h3 and Nr1h2 encoding transcription factors (SREBP1c and LXRα and LXRβ, respectively) that regulate the expression of lipogenic genes. Additionally, CES1 increased the expression of Acsl1 encoding an enzyme catalyzing fatty acid activation and the expression of Dgat1 and Dgat2 encoding enzymes catalyzing TG synthesis. Treatment of CES1-expressing cells with PPARγ antagonist (GW9662), LXR antagonist (GSK2033) or CYP27A1 inhibitor Felodipine prevented CES1-mediated fatty acid esterification into TG. Ces1d-deficient mice fed high-fat diet (HFD) presented with decreased expression of Nr1h3, Nr1h2, Srebf1c and reduced hepatic TG content. Felodipine and GSK2033 treatment eliminated the differential effects on TG concentration between wild-type and Ces1d-deficient hepatocytes. The results suggest that CES1/Ces1d activates PPARγ, LXR and SREBP1c pathways, thereby increasing TG synthesis and LD storage by augmenting fatty acid esterification. Full article

Background/Objectives: The interaction between brain-metastasizing melanoma cells and surrounding microglia shapes the immune tumor microenvironment and influences tumor progression. Gene expression analysis revealed that sphingosine-1-phosphate receptor 1 (S1PR1), encoding the S1P1 receptor, is upregulated in microglia upon interaction with melanoma cells. Here, we investigated the functions of S1P1 in microglia and its contribution to melanoma–microglia crosstalk. Methods: We examined the effects of S1P1 inhibition on microglia and four brain-metastasizing human melanoma cell lines in monocultures and co-cultures using the selective S1P1 antagonist NIBR0213 and S1PR1 gene knockdown. Results: We found that melanoma-secreted IL-6 upregulated S1PR1 expression in microglia. S1P1 inhibition increased expression of CD32, CD150, and CD163 in microglia; however, CD150 and CD163 upregulation was abolished in the presence of melanoma cells. S1P1 inhibition downregulated immunosuppressive and anti-inflammatory factors in microglia, including CD274, SOCS3, TGFBR1, TGFBR2, and JunB, promoting a pro-inflammatory phenotype. It also reduced viability of both melanoma and microglia cells, inducing apoptosis in melanoma-associated microglia, possibly via downregulation of CH25H, an upstream regulator of SREBPs. In co-cultures, melanoma cells were more sensitive than microglia to NIBR0213-induced growth arrest. In 3D spheroid cultures, NIBR0213 delayed melanoma–microglia aggregation. Combined treatment with the BRAF inhibitor Vemurafenib and NIBR0213 enhanced Vemurafenib efficacy in three of four melanoma lines. Conclusions: S1P1 contributes to the immunosuppressive phenotype of microglia. Inhibiting the S1P/S1P1 axis impairs viability and crosstalk between melanoma cells and tumor-activated microglia, offering a potential therapeutic strategy for melanoma brain metastases. Full article

This study evaluated the protective effects of magnolol, rutin, and gallic acid in broilers fed oxidized soybean oil. Four hundred seven-day-old male Arbor Acre broilers were randomly assigned to five treatments with eight replicates each: CON (4% fresh oil), OOC (4% oxidized oil), and OOC supplemented with 200 mg/kg of magnolol (MAG), rutin (RUT), or gallic acid (GAA). OOC significantly reduced 42-day body weight (BW), average daily gain (ADG), and average daily feed intake (ADFI), reduced serum antioxidant enzyme activities (T-SOD, GSH-Px) and elevated malondialdehyde and triglyceride levels. It also upregulated hepatic lipogenic (FASN, ACACA, SREBP-1) and inflammation (NF-κB1/2) genes, damaged intestinal morphology, reduced cecal Erysipelatoclostridium and Shuttleworthia abundances, and elevated oxidized lipids (9,10-DiHOME and prostaglandin G2) in breast muscle. All three polyphenols increased ADFI (22–42 d), ileal villus height and ZO-1 expression, while reducing serum triglycerides, ileal MDA, and hepatic NF-κB2 expression. Both magnolol and rutin further enhanced BW (42 d) and ADG (7–42 d), decreased ACACA expression, and elevated cecal Lachnoclostridium abundance. Additionally, magnolol significantly decreased the contents of 9,10-DiHOME and malondialdehyde, while rutin reduced prostaglandin G2 levels in the breast muscle. In conclusion, polyphenol supplementation alleviated oxidized oil-induced adverse effects, with magnolol and rutin being more effective. Full article

This study examined how the dietary lipid levels influence growth performance, lipid metabolism, oxidative response and hepatopancreatic health in Macrobrachium rosenbergii. A total of 720 post-larvae (0.86 ± 0.01 g) were divided into 4 groups according to the lipid levels in 43% protein-contained diets: 6% (L6), 8% (L8), 10% (L10), and 12% (L12). The results exhibited a significant increase in both the weight gain rate (WGR) and specific growth rate (SGR) in the L8 group (p < 0.05). Hepatopancreatic lipid metabolism genes (fas, acc, srebp1, and fabp) showed increased expression at higher dietary lipid levels (p < 0.05). The expression of ampk was significantly reduced, whereas the expression of atgl was increased in the L8 group (p < 0.05). Additionally, the activities of total superoxide dismutase (SOD), glutathione S-transferase (GST), and total antioxidant capacity (T-AOC) level were significantly higher in the L8 group, while the content of malondinaldehyde (MDA) was significantly reduced (p < 0.05). H&E staining of the hepatopancreas revealed that high-lipid diets resulted in severe hepatopancreas damage. Moreover, the L8 group exhibited consistently high cumulative survival rates under both ammonia nitrogen and high-temperature stress (p < 0.05). In conclusion, this study recommends a dietary lipid level of 8% to optimize growth performance in M. rosenbergii under high-density rearing conditions (70 prawns/m³). Full article

SIRT1-SREBP−1c/PGC−1α signaling is involved in the production of non-esterified fatty acids (NEFAs) and liver lipid metabolism disorders in ketotic calf. The molecules contained in extracellular vesicles (EVs) regulate intercellular communication, and research on calf hepatocytes−derived EVs has become a hot spot. We hypothesized that EVs in cell culture supernatants could affect lipid metabolism in hepatocyte models via SIRT1/SREBP−1c/PGC−1α signaling. Non-ketosis (NK, 0 mM NEFA) and clinical ketosis calf models (CK, 2.4 mM NEFAs) were established in vitro cultured calf hepatocytes and EVs were extracted from their supernatants as NK−derived EVs and CK−derived EVs, respectively. In vitro hepatocyte models, comprising a normal culture group (normal) and the group treated with NEFAs at 2.4 mM (2.4 NEFA), were treated with NK and CK−derived EVs. In addition, we transfected an SIRT1−overexpressing adenovirus into calf hepatocytes and determined the expression of key genes, enzymes, and proteins involved in the SIRT1/SREBP−1c/PGC−1α pathway. The results showed that the NK−derived EVs inhibited the expression of the SREBP−1c gene and protein and increased the expression of the SIRT1 and PGC−1α genes and proteins (p < 0.05). In contrast, CK−derived EVs induced lipid metabolism disorders in the normal hepatocyte group and aggravated NEFA-induced lipid metabolism imbalances in hepatocytes (p < 0.05). Moreover, overexpression of SIRT1 confirmed that EVs exert vital functions in hepatocyte lipid metabolism via SIRT1/SREBP−1c/PGC−1α signaling to regulate hepatocyte lipid metabolism. In summary, NK−derived EVs alleviated liver lipid metabolism disorders caused by NEFAs via modulation of SIRT1/SREBP−1c/PGC−1α signaling, while CK−derived EVs had the opposite effect. NK−derived EVs upregulated lipid oxidation-related genes and downregulated lipid synthesis-related genes, suggesting that NK−derived EVs could be used as biological extracts to alleviate lipid metabolism disorders in ketotic calf. Full article

Background: The gut-liver axis is essential for maintaining liver physiology, with the gut microbiota playing a central role in this bidirectional communication. Recent studies have identified microbiota-derived extracellular vesicles (EVs) as key mediators of inter-organ signaling. This study explored the impact of EVs from two beneficial Escherichia coli strains, the probiotic EcN and the commensal EcoR12, on hepatic metabolism and oxidative stress in healthy neonatal rats. Methods: EVs were administered orally during the first 16 days of life, and blood and liver samples were collected on days 8 and 16. Results: The results demonstrated that EVs significantly reduced intestinal permeability, as evidenced by decreased plasma zonulin levels. In the liver, EVs enhanced redox homeostasis by downregulating CYP2E1 and upregulating key antioxidant genes (SOD1, CAT, GPX). Furthermore, the treatment shifted liver metabolism toward an anti-lipogenic profile by inducing fatty acid oxidation genes (PPARA, CPT1A) and suppressing genes involved in de novo lipogenesis (SREBP1C, ACC1, FASN, CNR1). Importantly, markers of hepatic inflammation remained unchanged, indicating the safety of the intervention. In vitro experiments using human HepG2 cells supported these findings, further validating the antioxidant and metabolic effects of the EVs. Conclusions: Our results underscore the role of microbiota-derived EVs as important mediators of hepatic metabolic programming in healthy individuals via the gut-liver axis and highlight their potential as therapeutic postbiotic agents for management of fatty liver diseases. Full article

A fast-paced lifestyle contributes to heightened emotional stress, driving the demand for milder and safer cosmetic ingredients that can counteract stress-induced skin damage—a focus of cutting-edge research in the field. Aim: The aim was to elucidate the role and mechanistic basis of tea (Camellia sinensis) seed meal saponin (Sap) in regulating stress-induced sebum overproduction and inflammatory responses. Methods: The composition and chemical structure of Sap were analyzed using UV-vis absorption spectroscopy, Fourier-transform infrared spectroscopy (FT-IR), and ultra-high-performance liquid chromatography–mass spectrometry (UHPLC-MS). In vitro models of cortisone-induced excessive lipid accumulation and the tumor necrosis factor-alpha (TNF-α)-stimulated inflammatory models were established on sebaceous gland cells (SZ95) and normal human epidermal keratinocytes (NHEKs), respectively. Cortisol and inflammatory cytokine secretion levels in cells were detected using ELISA. Additionally, the signaling pathways were revealed by Western blot (WB) and real-time quantitative polymerase chain reaction (RT-PCR). Results: Five saponins were identified in the Sap extract, all belonging to the oleanolic-acid-type pentacyclic triterpenes. Sap treatment significantly attenuated cortisone-induced cortisol secretion and lipid accumulation in SZ95 sebocytes. Mechanistically, Sap inhibited the 11β-HSD1/SREBP-1 pathway, which mediates its sebosuppressive effects, while concurrently down-regulating the mRNA expression of key downstream transcription factors and enzymes, including SREBP-1, FAS, and ACC. Additionally, Sap treatment significantly attenuated TNF-α-stimulated cortisol secretion and inflammatory cytokine (IL-1β, IL-6, and IL-8) production in NHEK cells through the inhibition of the 11β-HSD1/TLR2/NF-κB signaling pathway. Conclusion: Sap demonstrated dual inhibitory effects, suppressing both emotional-stress-induced sebum overproduction and inflammatory cytokines secretion. Full article

Prostate cancer (PCa), the second leading cause of cancer-related mortality among men in the United States, is marked by profound metabolic reprogramming, particularly in lipid metabolism. This review highlights the pivotal role of altered lipid metabolic pathways, including de novo fatty acid synthesis, fatty acid uptake and transport, β-oxidation, and cholesterol metabolism, in the development, progression, and therapeutic resistance of PCa. Key enzymes and transcription factors, such as FASN, ACLY, SREBPs, and FABPs, which are mainly regulated by androgen receptor signaling, orchestrate a lipogenic phenotype that supports prostate tumor growth and survival. Crosstalk between lipid metabolism and the tumor microenvironment further promotes immune evasion and metastasis. The review also explores therapeutic opportunities in targeting lipid metabolic pathways, highlighting the preclinical and clinical advances in inhibiting FASN, SREBP1, SREBP2, HMGCR, and FABPs, as well as combinatorial strategies with conventional therapies. Understanding the impact of lipid metabolism on PCa pathogenesis provides a promising avenue for developing novel targeted and combinatorial interventions to improve clinical outcomes in PCa. Full article

Steamed ginger ethanolic extract (GGE03) has been shown to exert anti-obesity effects, yet its underlying molecular mechanisms remain unclear. This study investigates the metabolic impact of GGE03 on lipid metabolism, adipogenesis, and energy regulation in a high-fat diet (HFD)-induced obesity model. C57BL/6N mice were fed a control diet, a high-fat diet (HFD), or HFD supplemented with GGE03 (50, 100, or 200 mg/kg/day) for eight weeks. GGE03 significantly reduced body weight gain (HFD: 18.1 ± 0.3 g vs. HFD+GGE03 200 mg/kg/day: 13.4 ± 0.2 g, p < 0.05) and fat mass percentage (HFD: significantly higher vs. HFD+GGE03 50, 100, 200 mg/kg/day, p < 0.05). Serum glucose levels were decreased from 220.2 ± 8.2 mg/dL (HFD) to 169.6 ± 5.9 mg/dL (HFD+GGE03 200 mg/kg/day, p < 0.05), and triglyceride levels were reduced from 82.9 ± 4.2 mg/dL (HFD) to 57.2 ± 2.9 mg/dL (p < 0.05). Insulin resistance, as measured by HOMA-IR, was improved by up to 54.9% compared to the HFD (p < 0.05). Mechanistically, GGE03 administration increased AMPK phosphorylation (p-AMPK/AMPK ratio significantly elevated by HFD+GGE03 100 and 200 mg/kg/day, p < 0.05) and upregulated fatty acid oxidation gene expression (Cpt-1), while suppressing lipogenesis-related genes (Srebp-1c, Fas, and Acc1). GGE03 improved obesity-related metabolic disturbances in high-fat diet-induced mice, with beneficial effects associated with AMPK signaling and lipid metabolism. These findings suggest the potential of GGE03 as a functional food ingredient for obesity prevention and management. Full article

Dysregulation of hepatic lipid metabolism constitutes a central mechanism in the pathogenesis of metabolic dysfunction-associated steatotic liver disease (MASLD). 3,3′-Diindolylmethane (DIM), a bioactive compound abundant in dietary Brassica vegetables, exhibited protective effects on hepatocellular carcinoma and metabolic/inflammatory pathologies. Nevertheless, the effects of DIM on hepatic lipid metabolism and its underlying mechanisms remain unclear. Administration of DIM (50 mg/kg bw/day) prevented oxidative stress and hepatic lipid deposition in both high-fat diet (HFD)-fed wild-type (WT) and ob/ob mice. Lipidomics revealed that DIM diminished the lipogenesis and reshaped the hepatic lipid profile. Network pharmacology analysis identified the AMPK signaling pathway as the underlying mechanistic target for DIM in treating MASLD. In both HepG2 cells and mouse primary hepatocytes (MPH), DIM attenuated palmitic acid (PA)-induced cellular lipid accumulation, ROS generation, and reduction in oxygen consumption rate (OCR). These protective effects of DIM were diminished by co-treatment with Compound C (CC), a specific AMPK inhibitor. DIM administration enhanced AMPKα phosphorylation in vivo (WT/ob/ob mice) and in vitro (HepG2/MPH), concomitant with PPARα upregulation and SREBP1/ACC1 downregulation. CC abolished all DIM-induced molecular changes in vitro. Collectively, DIM alleviates hepatic lipid accumulation and oxidative stress in MASLD models through AMPK activation, subsequently modulating PPARα and SREBP1/ACC1 pathways. Full article