Search Results (34)

Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by abnormal hepatic lipid accumulation and is frequently driven by factors such as a high-fat diet (HFD). Total flavonoids of Apocynum venetum (TFAV), the bioactive constituents of a traditional medicinal plant, have demonstrated antioxidant and lipid-modulating properties. However, their therapeutic potential against MASLD and the underlying mechanisms are not explored. This study aims to evaluate the ameliorative effects of TFAV on HFD-induced MASLD utilizing both in vivo animal and in vitro cellular models. Methods: C57BL/6J were allocated to control, high-fat diet (HFD), TFAV (100 mg/kg/day), and TFAV intervention groups (25, 50, and 100 mg/kg/day). In vitro, WRL68 hepatocytes were stimulated with free fatty acids (FFAs) to establish a cellular model of steatosis. Liver function, serum lipid profiles, hepatic histopathology, and the AMPK signaling pathway were assessed. Results: TFAV intervention significantly improved serum biochemical profiles in the animal models; for instance, co-treatment with 100 mg/kg/day TFAV and HFD reduced TC, TG, and LDL-C levels by 20.59%, 45.26%, and 38.24% respectively (p < 0.05), and effectively alleviated hepatic steatosis and hepatocyte ballooning. Furthermore, TFAV markedly inhibited intracellular reactive oxygen species (ROS) levels and activated the AMPK signaling pathway (p < 0.05). This was accompanied by the downregulation of SREBP-1c and ACC expression (p < 0.05), as well as the upregulation of ATGL and CPT1α expression (p < 0.05). Conclusions: These results demonstrates that TFAV remodel hepatic lipid homeostasis by activating the AMPK signaling pathway, and exerting significant preventive and protective effects against the progression of HFD-induced MASLD in vivo. Full article

Obesity is associated with excessive lipid deposition in adipose tissue and the liver, leading to systemic metabolic disturbances. In this study, we investigated the anti-obesity efficacy of Tisochrysis lutea (TL) powder, standardized to fucoxanthin (12.18 ± 0.21 mg/g DW) and docosahexaenoic acid (DHA) (16.03 ± 0.49 mg/g DW), in a high-fat diet (HFD)-induced obesity model in C57BL/6N mice. TL supplementation (50–150 mg/kg) over eight weeks significantly reduced body weight gain by up to 63.2%, total white adipose tissue mass by 53.4%, and liver weight by 38.2% compared to the HFD control, without affecting renal safety markers. Histological examination revealed smaller adipocytes and diminished hepatic steatosis in TL-treated groups. Serum triglycerides and leptin concentrations were significantly lowered by 38.5% and 70.1%, respectively, while HFD-induced elevations of ALT and AST were reduced by 61.7% and 38.6%, respectively. At the transcriptional level, TL downregulated adipogenic markers including PPARγ, C/EBPα, and SREBP-1c by 46~54%, as well as lipogenic regulators including FAS and ACC1 by up to 72%. Furthermore, TL treatment upregulated the mRNA levels of HSL and AMPK 2.3- and 2.1-fold, respectively, compared to the HFD control. These findings indicate that fucoxanthin- and DHA-enriched TL powder improves obesity-related metabolic alterations by modulating lipid storage and utilization pathways, supporting its development as a marine-derived functional ingredient for metabolic health management. Full article

Nobiletin, a citrus-derived polymethoxylated flavone, has been reported to exert anti-obesity effects, but its molecular mechanisms remain poorly understood. This study aimed to investigate whether nobiletin suppresses adipogenesis and promotes browning in 3T3-L1 adipocytes by modulating exosomal microRNAs (miRNAs) and AMPK signaling. To this end, we treated 3T3-L1 adipocytes with various concentrations of nobiletin and evaluated gene and protein expression by RT-qPCR and Western blotting. Nobiletin significantly reduced intracellular lipid accumulation at 50 μM (p < 0.001) and downregulated key adipogenic transcription factors, PPARγ, C/EBPα, and SREBP-1c, and suppressed the lipogenic enzyme FAS, while activating the AMPK/ACC signaling pathway. Concomitantly, it enhanced the expression of thermogenic markers UCP-1, PRDM16, and PGC-1α, indicating a metabolic shift toward energy expenditure. Exosomal RNA-seq revealed 10 differentially expressed miRNAs, of which miR-181d-5p (3.1-fold) and miR-221-3p (2.4-fold) were upregulated, whereas miR-205-5p (−2.9-fold), miR-331-3p (−3.2-fold), miR-130b-3p (−2.6-fold), miR-143-5p (−2.9-fold), miR-183-3p (−2.8-fold), miR-196b-5p (−2.4-fold), miR-26b-3p (−2.2-fold), and miR-378d (−2.7-fold) were verified by RT-qPCR after nobiletin treatment (50 μM). These miRNAs are functionally associated with adipogenic and thermogenic pathways, supporting a regulatory role of the exosomal miRNA network in nobiletin’s action. Collectively, our results identify a novel exosome–miRNA–AMPK axis underlying the anti-adipogenic and browning-inducing activities of nobiletin, highlighting its potential as a therapeutic phytochemical for obesity prevention. Full article

Lipid metabolism and lipid-derived signaling together ensure cellular and systemic homeostasis. Their dysregulation causes obesity, type 2 diabetes, cardiovascular disease, NAFLD/MASH, and neurodegeneration throughout life. This review integrates central pathways, such as ACC–FASN-mediated de novo lipogenesis, lipid-droplet lipolysis, and mitochondrial and peroxisomal β-oxidation, and their regulation by insulin–PI3K–Akt, glucagon–cAMP–PKA, SREBPs, PPARs, and AMPK. We emphasize the mechanisms by which bioactive lipids like diacylglycerols, ceramides, eicosanoids, and endocannabinoids serve as second messengers linking nutrient state to insulin signaling, inflammation, and stress response; pathologic accumulation of these species enhances insulin resistance and lipotoxicity. Aging disrupts these axes via diminished catecholamine-stimulated lipolysis, defective fatty-acid oxidation, mitochondrial failure, and adipose depot redistribution, facilitating ectopic fat and postprandial dyslipidemia. We suggest a pathway-to-phenotype paradigm that connects lipid species and tissue environment to clinical phenotypes, allowing for mechanism-to-intervention alignment. Therapeutic avenues range from lipid lowering for atherogenic risk to novel agents targeting ACLY, ACC, FASN, CPT1, and nuclear receptors, with precision lifestyle intervention in diet and exercise. Translation is still heterogeneous because of isoform-dependent effects, safety trade-offs, and inconsistent adherence. We prioritize harmonization of lipidomics with multi-omics for stratifying patients, enriching responders, and bridging gaps between mechanistic understanding and clinical outcome, with focus on age-sensitive prevention and treatment for lipid-mediated 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

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

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

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

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

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

Background/Objective: This study examined the anti-obesity effect of royal jelly (RJ) in rats fed with a high-fat diet by targeting the major pathways involved in adipogenesis and lipolysis. In addition, it examined whether this effect is AMPK-dependent. Methods: Five groups of adult male albino rats were used (n = 6 each as 1); the control rats were fed with a normal diet (2.9 kcal), and the other groups were as follows: control + RJ (300 mg/kg), HFD (4.75 kcal), HFD + RJ (300 mg/kg), and HFD + RJ (300 mg/kg) + dorsomorphin (an AMPK inhibitor) (0.2 mg/kg). Results: RJ was administered orally to all rats. With no changes in food and energy intake, RJ significantly reduced gains in body weight, fat weight, body mass index (BMI), the Lee index, abdominal circumference (AC), and the adiposity index (AI). It also reduced fasting glucose and insulin levels, HOMA-IR, and the circulatory levels of free fatty acids (FFAs), triglycerides, cholesterol, and LDL-c in the HFD-fed rats. RJ also increased serum glycerol levels and adiponectin levels, but reduced the serum levels of leptin, IL-6, and TNF-α. Moreover, RJ reduced the secretion of IL-6 and TNF-α from isolated WAT. At the tissue level, the HFD + RJ rats exhibited a smaller adipocyte size compared to the HFD rats. At the molecular level, RJ increased the phosphorylation of AMPK, SREBP1, and ACC-1 and increased the mRNA and protein levels of HSL and ATG in the WAT of the HFD rats. In concomitance, RJ increased the mRNA levels of PGC-α1, reduced the protein levels of PPARγ, and repressed the transcriptional activities of PPARγ, SREBP1, and C/EBPαβ in the WAT of these rats. All the aforementioned effects of RJ were prevented by co-treatment with dorsomorphin. Conclusions: RJ exerts a potent anti-obesity effect in rats that is mediated by the AMPk-dependent suppression of WAT adipogenesis and the stimulation of lipolysis. Full article

Glycolipid metabolic disorders (GLMD) refer to a series of metabolic disorders caused by abnormal processes of glucose and lipid synthesis, decomposition, and absorption in the body, leading to glucose and lipid excess, insulin resistance, and obesity. Probiotic intervention is a new strategy to alleviate metabolic syndrome. Lactobacillus paracasei JY062 (L. paracasei JY062) was separated from the Tibet-fermented dairy products. The results demonstrated a strong ability to relieve blood glucose disorders, blood lipid disorders, and tissue damage. The LPH group had the best effect, significantly decreasing the total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), leptin, insulin, and free fatty acid (FFA) concentrations and increasing the high-density lipoprotein cholesterol, adiponectin, and GLP-1 level compared to HFD-group mice. L. paracasei JY062 could activate the APN-AMPK pathway, increased AdipoQ, AMPK GLUT-4, and PGC-1α mRNA expression and decreased SREBP-1c, ACC, and FAS mRNA expression. L. paracasei JY062 intervention decreased the relative abundance of harmful bacteria, increased the relative abundance of beneficial bacteria, and restored the imbalance of gut microbiota homeostasis caused by a high-glucose-fat diet. L. paracasei JY062 alleviated glucolipid metabolism disorders via the adipoinsular axis and gut microbiota. This study provided a theoretical basis for probiotics to ameliorate glucolipid metabolism disorders by regulating the adipoinsular axis. Full article

Acetate is associated with adipocyte differentiation and lipid deposition. To further develop this scientific point, obese mice on a high-fat diet were given an intragastric administration of acetate for 8 weeks and mouse adipose mesenchymal stem cells (mAMSCs) were treated with acetate for 24 h. The results showed that the body weight, food intake, Lee’s index, adipose tissue coefficient, liver index, blood lipid levels, insulin resistance, pro-inflammatory factors levels and fatty lesions in liver and adipose tissue in obese mice treated with acetate increased markedly, while anti-inflammatory factors levels and liver function decreased significantly (p < 0.05). The mRNA expression levels of PPAR-γ, C/EBP-α, SREBP, AFABP, FAS, ACC-1, SCD-1, LPL, LEPR, GPR41 and GPR43 genes in adipose tissue and mAMSCs were significantly increased, while the mRNA expression levels of HSL, CPT-1, CPT-2, AMPK, AdipoR1 and AdipoR2 genes were significantly reduced (p < 0.05). Except for AMPK-α signaling pathway proteins, the phosphorylation levels of p38 MAPK, ERK1/2, JNK and mTOR were significantly increased (p < 0.05) and these changes were dose-dependent. The findings indicated that acetate played a positive role in regulating adipocyte differentiation and lipid deposition by activating MAPKs and mTOR signaling pathways (the expression up-regulation of genes such as PPAR-γ, C/EBP-α and SREBP-1, etc.) and inhibiting the AMPK signaling pathway (the expression down-regulation of genes such as HSL, CPT-1 and AMPK-α, etc.). Full article