Search Results (168)

Obesity and associated metabolic disorders are rising globally, necessitating effective dietary strategies. CKDB-322, a formulation containing Lactiplantibacillus plantarum Q180 and Phaeodactylum tricornutum, was evaluated for anti-obesity efficacy using in vitro adipocyte differentiation and in vivo high-fat-diet (HFD)-induced obese mouse models. In 3T3-L1 cells, CKDB-322 suppressed adipogenesis by downregulating PPARγ and C/EBPα and enhancing glycerol release. In mice, 8 weeks of oral administration—particularly at the CKDB-322-M dose—significantly reduced body weight gain, adiposity, and serum glucose, triglyceride, and cholesterol levels without affecting liver function. Gene expression analysis revealed the strong inhibition of lipogenic markers (SREBP-1c, ACC, and FAS) in addition to activation of the fatty acid oxidation (CPT-1α and PPARα) and energy metabolism (PGC-1α and AMPK) pathways, with the most pronounced effects in the CKDB-322-M group, which also exhibited the greatest reduction in leptin. These molecular effects were confirmed histologically by decreased adipocyte hypertrophy and ameliorated hepatic steatosis. Collectively, these findings demonstrate that CKDB-322 exerts lipid-modulatory effects through multiple pathways, supporting its potential as a novel functional dietary ingredient for obesity and metabolic disorder prevention. Full article

Disused muscle atrophy (DMA) is characterized by skeletal muscle loss and functional decline due to prolonged inactivity. Though evidence remains limited, recent studies suggest that ferroptosis, an iron-dependent, lipid peroxidation-driven form of cell death, may contribute to DMA. Taurine, a natural amino acid enriched in energy drinks, can improve the proliferation and myogenic differentiation potential of myoblasts. This study aimed to investigate whether taurine supplementation could protect against DMA and explore its potential role in modulating ferroptosis. Using a hindlimb suspension-induced DMA model in male C57BL/6J mice (6–8 weeks old), we assessed muscle mass, function, ferroptosis-related markers, histopathological changes, and metabolic alterations. The results showed that taurine supplementation improved muscle strength and morphology while attenuating markers of ferroptosis, including iron accumulation, lipid peroxidation, and glutathione and related protein (NRF2, GPX4, and xCT) depletion. Metabolomic analysis suggested that taurine modulates disorders in glutathione and lipid metabolism, potentially associated with the regulation of the xCT-GSH-GPX4 and AMPK-ACC-ACSL4 pathways. While these findings support a protective role for taurine and a possible link between ferroptosis and DMA, further functional studies are needed to confirm causality and assess the compound’s translational potential. This study provides initial in vivo evidence implicating ferroptosis in DMA and highlights taurine as a promising candidate for future therapeutic exploration. Full article

Sarcopenic obesity (SO) is a metabolic disorder for which no effective pharmacological treatments are currently available. Cistanoside F (Cis), a phenoxyethanol-derived compound, remains relatively unexplored in the context of lipid metabolism regulation, as well as its potential mechanisms and therapeutic applications in metabolic disorders. Consequently, this study aimed to evaluate the potential of Cis in ameliorating the pathological manifestations of SO in C2C12 cells. Two classical adipogenic differentiation models using C2C12 cells were employed to quantitatively assess the ability of Cis to inhibit lipid droplet formation, utilizing Oil Red O staining coupled with high-content imaging analysis. Markers associated with adipogenic and myogenic differentiation were examined using quantitative real-time PCR and Western blotting. Our experimental findings demonstrated that Cis significantly attenuated lipid droplet accumulation and promoted muscle protein synthesis via the modulation of PPARγ, ATGL, CPT1b, and UCP1 expression during lipogenic differentiation of C2C12 cells. Cis significantly upregulated the phosphorylation and expression levels of key metabolic regulators, including p-AMPK/AMPK, p-ACC1/ACC1, and MHC. We identified a positive regulatory feedback mechanism between AMPK signaling and MHC expression in the adipogenic differentiation model, suggesting that Cis exerts its therapeutic effects through AMPK-dependent pathways. This is the first study to provide the first experimental evidence supporting the therapeutic potential of Cis for metabolic regulation, targeting adiposity reduction and muscle mass enhancement. Furthermore, Cis exhibited potent anti-inflammatory properties, as demonstrated by its ability to significantly downregulate proinflammatory mediators, including IL-6 and p-NF-κB/NF-κB, during adipogenic differentiation. These novel findings regarding the anti-inflammatory mechanisms of Cis will form the basis for our subsequent in-depth mechanistic investigations. Full article

Background: Diet-derived advanced glycation end products (dAGEs) are closely associated with obesity and metabolic disorders. This study investigates the therapeutic potential of myriocin (Myr), a sphingolipid synthesis inhibitor, in counteracting dAGE-induced obesity and its underlying mechanisms. Methods: Male C57BL/6J wild-type mice were randomly assigned to receive either a low-AGE diet or a high-AGE diet with or without the administration of myriocin for a duration of 24 weeks. At the end of the experimental period, blood samples, whole livers, and adipose tissues were harvested for subsequent biochemical, histological, and molecular analyses. Results: Using a 24-week high-AGE diet mouse model, we demonstrate that Myr significantly reduces body weight gain (by 76%) and adipose tissue accumulation, while alleviating hepatic steatosis. Myr improves glucose homeostasis by lowering fasting blood glucose (a 44.5% reduction), enhancing oral glucose tolerance, and restoring hepatic glycolysis/gluconeogenesis balance via upregulating glucokinase and suppressing G6pc. Notably, Myr reduces serum LDL-C, TG, and TC levels by 52.3%, 51.8%, and 48.8%, respectively, and ameliorates liver dysfunction as evidenced by normalized ALT/AST activities. Metabolomics reveal Myr reshapes amino acid, carbohydrate, and lipid metabolism pathways. Mechanistically, Myr suppresses lipogenesis by downregulating Srebp1, Fasn, and Acc, while activating AMPK-PGC1α signaling to enhance mitochondrial biogenesis (a 2.1-fold increase in mtDNA) and thermogenesis via Ucp1 upregulation in brown and white adipose tissues. Conclusions: Our findings unveil Myr as a novel dual regulator of lipid and glucose metabolism through AMPK-PGC1α-mediated mitochondrial activation, providing the first evidence of sphingolipid inhibition as a therapeutic strategy against dAGE-induced metabolic syndrome. This study establishes a multifaceted mechanism involving hepatic lipid regulation, adipose browning, and systemic metabolic reprogramming, advancing potential clinical applications for obesity-related disorders. Full article

The liver accounts for almost 95% of lipid metabolism in broilers and serves as a crucial metabolic organ. Stress, which occurs when broilers are exposed to a heated environment, inhibits liver metabolism, significantly impacting their growth. This experiment investigated the combination of GBE with TP to improve hepatic lipid metabolism in heat-stressed broiler chickens by inhibiting the AMPK/SREBP-1C/ACC pathway. Three hundred broilers were reared usually until 21 days and randomly divided into six groups, namely CON group, HS group, TP group (300 mg/kg), GBE100 group (GBE100 mg/kg + TP300 mg/kg), GBE300 group (GBE 300 mg/kg + TP 300 mg/kg), GBE600 (600 mg/kg + TP 300 mg/kg) groups, where the CON group was kept at 23 °C, and the HS group and the TP, GBE100, GBE300, and GBE600 groups of each medication group were kept at 35 ± 2 °C for 10 h per day. Liver and serum samples were extracted at 28 and 42 days of age, respectively. The results showed that, at 42 days of age, the GBE600 group exhibited significantly superior performance to the HS group in ADG, ADFI, and F/G (p < 0.01). Serum TG, TC, and LDL-C levels were significantly lower (p < 0.01), while HDL-C levels were significantly higher (p < 0.05). Additionally, the mRNA expression levels of LKB1, AMPK, SREBP-1C, and ACC were markedly reduced (p < 0.01). In contrast, the mRNA expression of HSL and CPT1A was significantly elevated (p < 0.01), indicating that the GBE600 was more effective in mitigating heat stress in broiler chickens at 42 days of age. It showed that the GBE600 was more effective in ameliorating heat stress in broilers at 42 days of age, thus providing an ethical basis for ameliorating the flocculation of hepatic lipid metabolism in heat-stressed broilers. Full article

Background/Objectives: Metabolites produced by gut microbiota play an important role in the crosstalk between the gut and other organs. Although HYA (10-hydroxy-cis-12-octadecenoic acid), a linoleic acid metabolite produced by lactic acid bacteria represented by Lactobacillus, has been shown to exert physiological effects such as metabolic improvement and anti-inflammation in the host, its direct action on adipose tissue and the mechanism remains unknown. Methods: The effect of HYA administration on adipocyte size in mice fed a high-fat diet was examined. In 3T3-L1 mature adipocytes treated with HYA, the amount of intracellular lipid droplets was evaluated by Oil red O staining, gene expression by real-time qPCR, phosphorylation of AMP-activated protein kinase (AMPK) by immunoblotting, and intracellular Ca²⁺ concentration with calcium imaging. Results: Administration of HYA, but not linoleic acid, to obese mice fed a high-fat diet significantly reduced adipocyte size. To investigate whether the inhibition of adipocyte hypertrophy by HYA has a direct effect on adipocytes, 3T3-L1 adipocytes were treated with HYA, which significantly decreased the amount of intracellular lipid droplets in these cells. Gene expression analysis by real-time PCR showed decreased expression of genes related to lipogenesis such as FAS and ACC1, and increased expression of CPT1A, which is involved in fatty acid oxidation. Mechanistically, HYA was found to activate AMPK in adipocytes by increasing intracellular Ca²⁺ concentration. Conclusions: HYA suppresses adipocyte hypertrophy by activating AMPK in adipocytes. HYA may be a potential therapeutic for obesity and related metabolic disorders. Full article

Background/Objectives: Obesity is a significant global health concern, and the natural bioactive compounds with anti-obesity effects remain challenging. This study aims to examine the anti-obesity effect and the potential mechanism of Vaccinium oldhamii fruit water extract (VOW). Methods: Lipid accumulation, AMP-activated protein kinase (AMPK) activity, and Wnt/β-catenin signaling were evaluated in 3T3-L1 cells. In high-fat and high-sucrose diet (HFHSD)-induced obese mice, body weight, food intake, fat weight, serum lipid profiles, and adipogenic transcription factors were assessed. The most effective VOW fraction was selected by Oil Red O (ORO) staining and its mechanism was studied in 3T3-L1 cells. Results: VOW treatment significantly inhibited cellular lipid accumulation and suppressed phosphorylation of AMPK and its downstream protein, acetyl-CoA carboxylase (ACC). VOW also decreased adipogenic-associated protein expressions such as the peroxisome proliferator-activated receptor-γ (PPAR-γ), CCAAT/enhancer-binding proteins α (C/EBP α), sterol regulatory element binding protein-1c (SREBP-1c), and fatty acid synthase (FAS). The enhanced effect of VOW was abolished by the knockdown of AMPK with siRNA. The inhibitory effect of VOW on differentiation depended on the treatment period, even though VOW treatment downregulated the C/EBP β expression at the early phase of differentiation. VOW dramatically reduced activation of AMPK, thereby downregulating adipogenic-associated proteins. Furthermore, the butanol fraction (BtOH) of VOW showed the most powerful effect of VOW dose-dependently reduced lipid accumulation by suppressing the phosphorylation of AMPK. Consistent with inhibited lipid accumulation in vitro, VOW reduced body weight and white adipose tissue weight in the HFHSD-induced obese animal model. Conclusions: Overall, our study suggested that the anti-adipogenesis effect of VOW and its BtOH fraction involved the activation of AMPK. Full article

Isoquercitrin, a flavonoid glycoside found in various plants, has demonstrated antioxidant, anti-inflammatory, and anticancer properties. However, its hepatoprotective effects and underlying mechanisms against oxidative liver injury remain unclear. In this study, we evaluated the antioxidant and hepatoprotective effects of isoquercitrin using integrated in silico, in vitro, and in vivo approaches. HepG2 cells exposed to arachidonic acid (AA) and iron exhibited oxidative stress-induced apoptosis, which was significantly attenuated by isoquercitrin treatment, as evidenced by increased cell viability and reduced apoptosis-related protein alterations. Isoquercitrin decreased reactive oxygen species (ROS) generation and preserved mitochondrial function in a dose-dependent manner. Molecular docking and Western blot analyses revealed that isoquercitrin activates the LKB1/AMPK pathway, increasing phosphorylation of AMPK and its downstream target ACC, thereby modulating energy metabolism and reducing oxidative stress. This activation was LKB1 dependent, as confirmed in LKB1-deficient HeLa cells. Additionally, isoquercitrin modulated the YAP signaling pathway in hepatic cells. In vivo, isoquercitrin protected mice against carbon tetrachloride-induced liver injury, reducing serum ALT and AST levels and improving histopathological features. These findings suggest that isoquercitrin exerts hepatoprotective effects by activating the LKB1/AMPK pathway and modulating metabolic enzymes, highlighting its potential as a therapeutic agent against oxidative liver damage. Full article

This experiment was arranged to explore the impacts of dietary MHA on liver lipid metabolism in largemouth bass. A total of 480 fish (14.49 ± 0.13 g) were randomly allocated into four groups, each with three replicates. They were then given four different diets containing graded levels of MHA (0.0, 3.0, 6.0, and 9.0 g/kg) for 84 days. The results showed that dietary MHA increased hepatic lipid vacuoles and lipid content (p < 0.05). Dietary supplementation with MHA 9.0 g/kg diets increased the activities of acetyl-coA carboxylase (ACC), fatty acid synthase (FAS), and stearoyl-coA desaturase 1 (SCD-1). Dietary MHA up-regulated the mRNA expressions of liver lipid synthesis (ACC, FAS, SCD-1 and SREBP-1c) (p < 0.05). Furthermore, compared with the 0.0 g/kg diet group, the group supplemented with 9.0 g/kg MHA in the diet exhibited a significant decrease in the activities of liver lipid-oxidation-related enzymes (acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), and stearoyl-CoA desaturase 1 (SCD-1), as well as HSL and CPT1) and the gene expressions of ATGL, HSLa, HSLb, CPT1a, and PPARα (p < 0.05). Additionally, the mRNA expressions and protein levels of SIRT1 and AMPK in the 9.0 g/kg MHA-supplemented group were significantly lower than those in the 0.0 g/kg diet group (p < 0.05). Overall, the present results suggested that dietary MHA could increase lipid accumulation through regulating SIRT1/AMPK signaling pathways in the livers of largemouth bass. Full article

Pyranoanthocyanins exhibit greater bioactivity compared to monomeric anthocyanins, yet the lipid-lowering effects of pyranoanthocyanin Vitisin A, a primary derivative found in aged red wines, have not been extensively studied in vivo. This study evaluated the triglyceride-lowering effects of Vitisin A and its anthocyanin counterpart Cyanidin-3-O-glucoside (C3G) in both free fatty acid -induced HepG2 cells and high-fat diet-fed ApoE^-/- mice, with a focus on their roles in lipid metabolism. In vitro, Vitisin A significantly reduced triglyceride levels and lipid accumulation in HepG2 cells compared to C3G at equivalent concentrate. In vivo, dietary supplementation with 100 mg/kg of Vitisin A reduced body weight gain and plasma triglyceride levels by 19.6% and 29.5%, respectively, whereas no significant effects were observed with C3G. Mechanistically, Vitisin A markedly inhibited hepatic de novo lipogenesis (DNL) by activating the AMPK/ACC signaling pathway and downregulating FASN expression. Concurrently, Vitisin A enhanced fatty acid β-oxidation more robustly than C3G by upregulating CPT-1A via AMPK/SIRT1/PGC-1α and PPAR-α/PGC-1α pathways. Both Vitisin A and C3G driving peroxisomal β-oxidation of very-long-chain fatty acids. In summary, Vitisin A demonstrated superior triglyceride-lowering effects compared to C3G, primarily through dual mechanisms of inhibiting hepatic DNL and enhancing fatty acid β-oxidation. Full article

Hyperlipidemia, characterized by an abnormal lipid metabolism, is related to multiple cardiovascular diseases that pose challenges to global public health. Macadamia oil (MO), rich in monounsaturated fatty acids (around 80%), is regarded as a functional oil used to regulate lipid accumulation. Nonetheless, the lipid-lowering mechanism of MO is still unknown. Therefore, the lipid-lowering effects of MO in high-fat diet (HFD)-induced hyperlipidemic mice were evaluated in this study. The results revealed that MO could effectively reduce body weight and the organ index and improve serum lipid levels by reducing total cholesterol, triglycerides, and low-density lipoprotein cholesterol levels and elevating high-density lipoprotein cholesterol levels. Additionally, MO supplementation could improve abnormal liver function caused by hyperlipemia, characterized by decreased liver enzyme levels, including alanine aminotransferase and aspartate aminotransferase. Meanwhile, MO also exhibited an inhibitory effect on oxidative stress and lipid accumulation caused by an HFD. Moreover, findings from qRT-PCR and Western blotting analyses suggest that MO supplementation markedly prevented hyperlipidemia by inhibiting the expression of AMPK pathway-related genes, SREBP-1c, FAS, ACC, and PPAR-γ, as well as upregulating the levels of Nrf2, HO-1, and γ-GCS. These results indicate that MO attenuates lipid accumulation in vivo via AMPK/Nrf2 pathway activation, suggesting that MO could serve as a dietary supplementation or medication for treating hyperlipidemia. Full article

Objectives: Isostrictiniin (ITN), a natural polyphenol extracted from Nymphaea candida (snow-white waterlily), has antioxidant and hepatoprotective activities that may be beneficial in treating metabolic dysfunction-associated steatotic liver disease (MASLD). This study aimed to investigate the protective effects of ITN on high-fat, high-sugar diet (HFSD)-induced steatosis in MASLD mice and its mechanisms. Methods: Kunming mice were randomly divided into normal control and HFSD groups. After being fed for 4 weeks, the HFSD group was randomly divided into model, atorvastatin calcium (ATC; 10 mg/kg), and ITN (25, 50, and 100 mg/kg) groups. After continued feeding for 4 weeks, the biochemical indexes in the mice were determined. Results: Compared with the model group, the liver index; FBG; HOMA-IR; serum AST, ALT, TG, TC, and LDL-C; and liver MDA, IL-6, TNF-α, and IL-1β levels in the ITN (25, 50, and 100 mg/kg) and ATC (10 mg/kg) groups were significantly decreased (p < 0.05), while serum HDL-C and liver SOD and GSH-Px levels were increased (p < 0.05). Pathological observation showed that ITN treatment mitigated the lipid liver deposition in the HFSD mice. Moreover, ITN could upregulate liver-tissue p-AMPK/AMPK protein expression in the HFSD-induced MASLD mice and downregulate SREBP-1c and ACC levels (p < 0.05). Conclusions: ITN can significantly improve MASLD mice, and its mechanism may be related to the regulation of the AMPK/SREBP-1c/ACC pathway. Full article

This study investigated the effects of acupuncture and warm acupuncture on the expression and mechanism of the AMP-activated protein kinase (AMPK) signalling pathway associated with lipid accumulation in the liver tissue of rats with metabolic dysfunction-associated fatty liver disease (MAFLD) induced by a high-fat diet. Sprague–Dawley rats were categorised into four groups: control (CON), untreated MAFLD (MAFLD), and two MAFLD groups treated with acupuncture (ACU) and warm acupuncture (WA). The treatment groups underwent 16 application sessions over 8 weeks at the SP9 and BL18 acupoints. We measured the expression levels of AMPK, sterol regulatory element-binding protein1 (SREBP1), acetyl-coenzyme A carboxylase (ACC), peroxisome proliferator-activated receptorα (PPARα), carnitine palmitoyltransferase1 (CPT1), and CPT2. AMPK was activated in both ACU and WA groups. WA downregulated both SREBP1 and ACC expression at the protein level, whereas the acupuncture treatment downregulated SREBP1 expression. Additionally, WA selectively induced the activation of signalling pathways related to AMPK, PPARα, CPT1, and CPT2 at the mRNA level. Histological observations confirmed that fat accumulation was reduced in both the ACU and the WA groups compared to the MAFLD group. The WA treatment-promoted amelioration of HFD-induced MAFLD may be related to the activation of the AMPK/SREBP1/ACC pathway in the liver. Full article

The major components of magnolia flower extracts (MFEs) were classified into four substances, such as flavonoids, phenylethanoid glycoside derivatives (PhGs), caffeoylquinic acids (CQAs), and others, in our previous study. The chemical components of MFEs, including the rutin of flavonoid, acteoside and isoacteoside of PhGs, and caffeyolquinic acids, are reported to have physiological effects on anti-obesity effects. The anti-obesity effect of fresh and browned Magnolia denudata flower extracts (FMFE and BMFE, respectively) was investigated in 3T3-L1 adipocytes. The treatment concentrations of FMFE and BMFE were 200 and 400 μg/mL, respectively, as determined with the WST-1 assay. Intracellular lipid accumulation in 3T3-L1 cells was inhibited with the treatment of MFEs, including FMFE and BMFE, as observed with an image of the culture plate, using an optical microscope and Oil red O staining. The expression of the adipogenic target genes involved in adipocyte differentiation, including PPARγ, C/EBPα, perilipin, FABP4, FAS, HSL, and SREBP-1, was suppressed with the treatment of MFEs. Additionally, the phosphorylation of AMPK and ACC in 3T3-L1 cells was significantly increased following treatment with the MFEs. These results suggest that both MFEs have a potential for physiological effects on anti-obesity activity. Full article

In recent years, the prevalence of non-alcoholic fatty liver disease (NAFLD) has risen annually, yet due to the intricacies of its pathogenesis and therapeutic challenges, there remains no definitive medication for this condition. This review explores the intricate relationship between the intestinal microbiome and the pathogenesis of NAFLD, emphasizing the substantial roles played by Lactobacillus plantarum and Bifidobacterium bifidum. These probiotics manipulate lipid synthesis genes and phosphorylated proteins through pathways such as the AMPK/Nrf2, LPS-TLR4-NF-κB, AMPKα/PGC-1α, SREBP-1/FAS, and SREBP-1/ACC signaling pathways to reduce hepatic lipid accumulation and oxidative stress, key components of NAFLD progression. By modifying the intestinal microbial composition and abundance, they combat the overgrowth of harmful bacteria, alleviating the inflammatory response precipitated by dysbiosis and bolstering the intestinal mucosal barrier. Furthermore, they participate in cellular immune regulation, including CD4⁺ T cells and Treg cells, to suppress systemic inflammation. L. plantarum and B. bifidum also modulate lipid metabolism and immune reactions by adjusting gut metabolites, including propionic and butyric acids, which inhibit liver inflammation and fat deposition. The capacity of probiotics to modulate lipid metabolism, immune responses, and gut microbiota presents an innovative therapeutic strategy. With a global increase in NAFLD prevalence, these insights propose a promising natural method to decelerate disease progression, avert liver damage, and tackle associated metabolic issues, significantly advancing microbiome-focused treatments for NAFLD. Full article