Search Results (211)

As high-quality sheep germplasm resources in China, Hu sheep are characterized by fast growth and development, high fecundity, and tolerance to drought and cold. Tibetan sheep, adapted to high-altitude environments, have developed strong environmental adaptability. To explore the differences in the interaction among rumen microbial flora, hepatic gluconeogenesis, and mitochondrial function between Tibetan sheep and Hu sheep in the Qinghai–Tibet Plateau, this study systematically compared and analyzed the rumen flora density, key enzyme activities related to hepatic gluconeogenesis and mitochondrial function, and the expression levels of related genes in Tibetan sheep and Hu sheep under identical feeding management conditions, followed by correlation analysis. The results showed that Hu sheep had significantly higher densities of Ruminobacteramylophilus (Ram) and Fibrobacter succinogenes (Fs) associated with starch and protein degradation (p < 0.01). The expression levels of Forkhead box O1 (FOXO1), pyruvate carboxylase (PC) activity, and adenosine triphosphate (ATP) content were also significantly higher than those in Tibetan sheep (p < 0.01). In contrast, Tibetan sheep had higher densities of Butyrivibrio fibrisolvens (Bf), Ruminococcus albus (Ra), Ruminococcus flavefaciens (Rf), etc., related to cellulose degradation (p < 0.01). The gluconeogenesis-related genes, Glucose-6-phosphatase catalytic subunit 1 (G6PC1) and phosphoenolpyruvate carboxykinase1 (PCK1), and the activities of phosphoenolpyruvate carboxykinase (PEPCK) and fructose-1,6-bisphosphatase (FBPase) were significantly higher in Tibetan sheep than in Hu sheep (p < 0.01). Mitochondrial function-related genes Mitofusin-1 (Mfn1), Mitofusin-2 (Mfn2), subunit 6 of ATP synthase (ATP6), cytochrome b (Cytb), etc., also showed significantly higher expression in Tibetan sheep (p < 0.01). While no significant differences were observed in the contents of citric acid (CA), pyruvic acid (PA), glucose (Glu), etc. (p > 0.05). Correlation analysis indicated that rumen flora was associated with the key enzyme activities and gene expressions of hepatic gluconeogenesis and mitochondrial function to varying degrees. In summary, Tibetan sheep exhibit strong fiber degradation capacity, the efficient utilization of gluconeogenic intermediates, and mitochondrial oxidative phosphorylation (OXPHOS) ability, forming adaptive strategies for high-altitude environments. By contrast, Hu sheep show efficient protein and starch degradation capacity, thereby enhancing the supply of gluconeogenic precursors. It is indicated that when introducing Hu sheep to high-altitude areas, dietary intervention can be used to regulate rumen microorganisms, such as increasing fiber-decomposing bacteria or enhancing mitochondrial oxidative capacity, to counteract metabolic limitations induced by hypoxia. Full article

This study investigated the effects of dietary carbohydrate levels (control 8.13%, HG1 12.03%, and HG2 14.15%) on growth performance and glutamate metabolism in Chinese perch (S. chuatsi) (initial weight: 39.12 ± 0.25 g) reared at 12–15 °C. Diets were isonitrogenous (49% protein). After 8 weeks, the HG1 group optimized weight gain rate (WGR), specific growth rate (SGR), and protein efficiency ratio (PER), while reducing feed conversion ratio (FCR). HG1 and HG2 groups reduced liver glutamate/glutamine levels while downregulating the expression of key ammonia-metabolizing genes (gs, gdh, and ampd), collectively suppressing glutamate-mediated ammonia excretion. HG1 and HG2 groups enhanced glycolysis (upregulated gk and pk) coupled with suppressed gluconeogenesis (decreased PEPCK and G6Pase activities) in the liver. Concurrent downregulation of proteolytic markers (mafbx and murf1) in the muscle indicated improved protein conservation efficiency in the HG1 and HG2 groups. The HG1 diet optimally enhances growth by promoting glycolysis, reducing ammonia excretion, and improving feed efficiency. The insights gained from this research will be used to refine the low-temperature culture feed for Chinese perch, aiming to decrease ammonia and nitrogen emissions, thereby advancing the practice of low-ammonia emission culture for this species. 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 primary active compound in vine tea is dihydromyricetin (DMY), which has a longstanding history as a dietary supplement and traditional ethnic medicine. However, the precise molecular mechanism by which vine tea dihydromyricetin extract (VDMY) regulates glucolipid metabolic disorder remains unclear. In this study, we first assessed the effect of VDMY on various physiological parameters in db/db mice, followed by RNA sequencing (RNA-seq) to identify key signaling pathways affected by VDMY in liver tissues. We also examined the impact of VDMY on the liver’s TLR4/MyD88/NF-κB and FOXO1 pathways using Western blotting. Our results showed that VDMY significantly reduced fasting blood glucose (FBG), total cholesterol (TC), triglycerides (TGs), and low-density lipoprotein cholesterol (LDL-C), while increasing high-density lipoprotein cholesterol (HDL-C) levels. Additionally, VDMY enhanced the liver’s antioxidant capacity by upregulating superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH), while lowering malondialdehyde (MDA), alanine aminotransferase (ALT), and aspartate aminotransferase (AST), thus alleviating liver damage. RNA-seq analysis further revealed that VDMY influenced multiple biological processes, including transcription, glycolysis, gluconeogenesis, and redox reactions, suggesting that its effects may be mediated through the TLR4/MyD88/NF-κB and FOXO1 pathways. Additionally, Western blot analysis revealed that VDMY effectively downregulated the expressions of TLR4, MyD88, NF-κB, and FOXO1 proteins in the liver of db/db mice, indicating that VDMY could target these pathways to intervene glucolipid metabolism dysfunction. Full article

Postnatally, glucagon acutely lowers plasma amino acid (AA) concentrations by stimulating hepatic AA catabolism, but its fetal actions remain unclear. This study tested whether a 2 h fetal glucagon infusion would stimulate hepatic AA catabolism and inhibit placental AA transfer. Late-gestation pregnant sheep (0.9 gestation) underwent surgical, vascular catheterization and received fetal glucagon (n = 8) or vehicle infusions (n = 8) in a crossover design with a 48 h washout period. Nutrient uptake and utilization were assessed during each infusion, and fetal liver and placental tissue were collected post-infusion under hyperglucagonemic (n = 4) or vehicle (n = 4) conditions. Glucagon receptor was identified in fetal hepatocyte and trophoblast cells. Glucagon reduced fetal plasma AA concentrations by 20% (p = 0.0103) and increased plasma glucose by 47% (p = 0.0152), leading to a three-fold rise in fetal plasma insulin (p = 0.0459). Hepatic gene expression associated with AA catabolism and gluconeogenesis increased (p < 0.0500) following glucagon infusion, and hepatic metabolomic analysis showed enrichment in AA metabolism pathways. However, placental AA transfer was unaffected by 2 h fetal glucagon infusions. In conclusion, a 2 h glucagon infusion stimulates hepatic glucose production and enhances AA catabolism in the fetal liver, lowering plasma AA concentrations. The primary acute effects of fetal glucagon are hepatic, as placental AA transfer is unchanged. Full article

Anadromous migration toward riverine tributaries is often challenged by altered environmental cues, food scarcity, and energy demands, sometimes at the expense of life itself. Tenualosa ilisha (Clupeiformes: Dorosomatidae), the national fish of Bangladesh, an anadromous shad, offers a model for understanding the molecular mechanisms of migration. To this end, we present a chromosome-level genome of T. ilisha and compare its transcriptomic imprints from muscle and liver across environments to trace the physiological shifts driving the migration. We observed rapid expansion of gene families to facilitate efficient signaling and osmotic balance, as well as a substantial selection pressure in metabolism regulatory genes, potentially relevant to a highly anadromous fish. We detected 1298 and 252 differentially expressed transcripts between sea and freshwater in the liver and muscle of T. ilisha, respectively, reflecting habitat and organ-specific adaptations. Co-expression analysis led us to hypothesize that the strength required for breeding migration toward upstream rivers is fueled by muscle protein catabolism forming ubiquitin-proteasomal complexes. In the liver, we observed a group of genes promoting fatty acid (FA) synthesis significantly in the riverine habitat. Regulation of FADS2 and ELOVL2 in the river reasoned the natural abundance of LC-PUFAs with better energy utilization in T. ilisha. Moreover, active gluconeogenesis and reduced insulin signaling in the liver are possibly linked to glucose homeostasis, potentially induced by prolonged starvation during migration. These genomic resources will accelerate the future evolutionary and functional genomics studies of T. ilisha. Full article

Endoplasmic reticulum (ER) stress significantly affects liver metabolism, often leading to disorders such as hepatic steatosis. Tunicamycin (TM), a known ER stress inducer, is frequently used to model metabolic stress, but its specific effects on liver energy homeostasis remain unclear. This study investigates how farnesol (FOH), a natural compound with antioxidant and anti-inflammatory properties, counteracts TM-induced ER stress and its associated metabolic disruptions in the liver. Using both primary hepatocytes and a mouse model, this study demonstrates that TM treatment caused upregulation of ER stress markers, including ATF4, and disrupted genes related to lipid metabolism and gluconeogenesis. Co-treatment with FOH reduced these stress markers and restored the expression of metabolic genes. In vivo, FOH treatment alleviated oxidative stress, reduced lipid accumulation, and restored normal glycogen and lipid metabolism. Histological analysis further confirmed that FOH preserved liver architecture and minimized cellular damage. FOH also stabilized serum lipid profiles and modulated key metabolic biomarkers, suggesting its protective role against TM-induced liver injury. These findings suggest that FOH has therapeutic potential in mitigating ER stress-related metabolic dysfunctions, offering promising insights for the treatment of liver diseases linked to metabolic stress. Full article

Neonatal mammals must rapidly adapt to significant physiological changes during the transition from the intrauterine to extrauterine environments. This adaptation, particularly in the metabolic and respiratory systems, is essential for survival. MicroRNAs (miRNAs) are small noncoding RNAs that regulate various physiological and pathological processes by binding to the 3′ untranslated regions of mRNAs. This study aimed to identify miRNAs involved in the early extrauterine adaptation of neonatal piglets and explore their functions. We performed small RNA sequencing on six tissues (heart, liver, spleen, lung, multifidus muscle, and duodenum) from piglets 24 h before birth (day 113 of gestation) and 6 h after birth. A total of 971 miRNA precursors and 1511 mature miRNAs were identified. Tissue-specific expression analysis revealed 881 tissue-specific miRNAs and 164 differentially expressed miRNAs (DE miRNAs) across the tissues. Functional enrichment analysis showed that these DE miRNAs are significantly enriched in pathways related to early extrauterine adaptation, such as the NFκB, PI3K/AKT, and Hippo pathways. Specifically, miR-22-3p was significantly upregulated in the liver post-birth and may regulate the PI3K/AKT pathway by targeting AKT3, promoting gluconeogenesis, and maintaining glucose homeostasis. Dual-luciferase reporter assays and HepG2 cell experiments confirmed AKT3 as a target of miR-22-3p, which activates the AKT/FoxO1 pathway, enhancing gluconeogenesis and glucose production. Furthermore, changes in blood glucose and liver glycogen levels in newborn piglets further support the role of miR-22-3p in glucose homeostasis. This study highlights the importance of miRNAs, particularly miR-22-3p, in the early extrauterine adaptation of neonatal piglets, offering new insights into the physiological adaptation of neonatal mammals. Full article

Type 2 diabetes mellitus (T2DM) is an intricate disease correlated with many metabolic deregulations, including disordered glucose metabolism, oxidative stress, inflammation, and cellular apoptosis due to hepatic gluconeogenesis aberrations. However, there is no radical therapy to inhibit hepatic gluconeogenesis disturbances yet. We thus sought to probe the effectiveness and uncover the potential mechanism of quercetin (QCT) and silk sericin (SS) in mitigating hyperglycemia-induced hepatic gluconeogenesis disorder, which remains obscure. Administration of QCT and SS to diabetic male albino rats markedly restored the levels of glucose, insulin, advanced glycation end-products (AGEs), liver function enzymes, alpha-fetoprotein (AFP), globulin, and glycogen, in addition to hepatic carbohydrate metabolizing enzymes and gluconeogenesis in comparison with diabetic rats. Furthermore, treatment with QCT and SS modulated hepatic malondialdehyde (MD), reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), nitric oxide, tumor necrosis factor-alpha (TNF-α), and interleukin-1β (IL-1β), in addition to serum interleukin-6 (IL-6) and cyclooxygenase-2 (COX-2), implying their effectiveness in safeguarding cells against oxidative impairment and inflammation. Remarkably, QCT and SS treatments led to the upregulation of expression of phosphatidylinositol 3-kinases (PI3K), phospho-Akt (p-Akt), and forkhead box-O1 (FOXO1) genes in hepatic tissues compared to diabetic rats, orchestrating these singling pathways for curtailing hyperglycemia and pernicious consequences in hepatic tissues. Importantly, immunohistochemical investigations exhibited downregulation of caspase-3 expression in rats treated with QCT and SS compared to diabetic animals. Beyond that, the histopathological results of hepatic tissues demonstrated notable correlations with biochemical findings. Interestingly, the in silico results supported the in vivo findings, showing notable binding affinities of QCT and SS to PI3K, GPx, and TNF-α proteins. These results imply that QCT and SS could mitigate oxidative stress and inflammation and regulate hepatic gluconeogenesis in diabetic rats. However, QCT revealed greater molecular interactions with the studied proteins than SS. Overall, our results emphasize that QCT and SS have significant therapeutic effects on attenuating hyperglycemia-induced hepatic gluconeogenesis, with QCT showing superior effectiveness. Full article

To explore the molecular targets for regulating glucose metabolism in carnivorous fish, the turbot (Scophthalmus maximus) was selected as the research object to study. Farnesoid X receptor (FXR; NR1H4), as a ligand-activated transcription factor, plays an important role in glucose metabolism in mammals. However, the mechanisms controlling glucose metabolism mediated by FXR in fish are not understood. It was first found that the protein levels of FXR and its target gene, small heterodimer partner (SHP), were significantly decreased in the high-glucose group (50 mM, HG) compared with those in the normal glucose group (15 mM, CON) in primary hepatocytes of turbot. By further exploring the function of FXR in turbot, the full length of FXR in turbot was cloned, and its nuclear localization function was characterized by subcellular localization. The results revealed that the FXR had the highest expression in the liver, and its capability to activate SHP expression through heterodimer formation with retinoid X receptor (RXR) was proved, which proved RXR could bind to 15 binding sites of FXR by forming hydrogen bonds. Activation of FXR in both the CON and HG groups significantly increased the expression of glucokinase (gk) and pyruvate kinase (pk), while it decreased the expression of cytosolic phosphoenolpyruvate carboxykinase (cpepck), mitochondrial phosphoenolpyruvate carboxykinase (mpepck), glucose-6-phosphatase 1 (g6pase1) and glucose-6-phosphatase 2 (g6pase2), and caused no significant different in glycogen synthetase (gs). ELISA experiments further demonstrated that under the condition of high glucose with activated FXR, it could significantly decrease the activity of PEPCK and G6PASE in hepatocytes. In a dual-luciferase reporter assay, the FXR could significantly inhibit the activity of G6PASE2 and cPEPCK promoters by binding to the binding site ‘ATGACCT’. Knockdown of SHP after activation of FXR reduced the inhibitory effect on gluconeogenesis. In summary, FXR can bind to the mpepck and g6pase2 promoters to inhibit their expression, thereby directly inhibiting the gluconeogenesis pathway. FXR can also indirectly inhibit the gluconeogenesis pathway by activating shp. These findings suggest the possibility of FXR as a molecular target to regulate glucose homeostasis in turbot. Full article

This study aimed to ascertain the potential benefits of green radish polysaccharide (GRP) in treating alcoholic liver disease (ALD) in mice and explore its mechanism of action. Using biochemical analysis, high-throughput sequencing of gut microbiota, and gas chromatography–mass spectrometry to measure short-chain fatty acids (SCFAs) in feces, we found that GRP intervention significantly improved lipid metabolism and hepatic function in mice subjected to excessive alcohol intake. The GRP intervention reduced malondialdehyde levels by 66% and increased total superoxide dismutase levels by 22%, thereby mitigating alcohol-induced oxidative stress. Furthermore, GRP intervention in mice with alcohol consumption resulted in a reduction in tumor necrosis factor, interleukin 6, and lipopolysaccharide levels by 12%, 9%, and 25%, respectively, effectively attenuating alcoholic liver inflammation. 16S rRNA amplicon sequencing demonstrated that excessive alcohol consumption markedly altered the gut microbiota composition in mice. The GRP treatment resulted in a significant reduction in the number of beneficial bacteria (Lactobacillus and Lachnospiraceae_NK4A136_group) and an increase in the proportion of harmful bacteria (Muribaculaceae and Verrucomicrobiota). The metabolomic analyses of the SCFAs demonstrated an increase in the contents of SCFAs, acetic acid, propionic acid, and butyric acid, following GRP supplementation. Furthermore, the metabolic levels of cholinergic synapses and glycolysis/gluconeogenesis were found to be modulated. In conclusion, these findings suggest that GRP may attenuate alcohol-induced oxidative damage in the liver by modulating the gut microbiota and hepatic metabolic pathways. This may position GRP as a potential functional component for ALD prevention. Full article

Background/Objectives: The Xizang sheep is a unique breed of sheep in the highland regions of China that has gradually developed physiological characteristics adapted to the plate environment through long-term natural selection and artificial breeding. However, little is known about the molecular basis of metabolic adaptation to seasons in Xizang sheep. Methods: In this study, liver tissues from Xizang sheep in summer (SL) and autumn (AL) were selected for transcriptome sequencing to explore the metabolic adaptability of Xizang sheep to seasons. Results: The results showed that a total of 12,046 differentially expressed genes (DEGs) were identified, with 1123 genes significantly upregulated and 951 genes significantly downregulated in autumn. The top five pathways enriched for DEGs were Metabolic pathways, Phagosome, Valine, leucine and isoleucine degradation, Propanoate metabolism, and Fatty acid metabolism, which are involved in immune regulation, fat oxidation, and synthesis. The reduction in lipid synthesis, fatty acid oxidation, and fat breakdown metabolism promotes gluconeogenesis by inhibiting the Peroxisome proliferator-activated receptors (PPAR) and Phosphoinositide 3-kinase- Protein kinase B (PI3K-Akt) signaling pathways. Conclusions: This process helps to maintain the whole-body energy homeostasis of Xizang sheep, facilitating their adaptation to the seasonal changes in the extreme high-altitude environment. These findings provide foundational data for studying the molecular mechanisms of metabolic adaptation to seasons in ruminants. Full article

Imeglimin promotes glucose-stimulated insulin secretion in the pancreas in a glucose-dependent manner and inhibits gluconeogenesis in the liver. Meanwhile, imeglimin can improve mitochondrial function in hepatocytes. We used a nondiabetic metabolic dysfunction-associated steatohepatitis (MASH) model to examine the effects of imeglimin on MASH independent of its glucose-lowering action. Mice fed a choline-deficient high-fat diet (CDA-HFD) were orally administered imeglimin (100 and 200 mg/kg twice daily), and MASH pathophysiology was evaluated after 8 weeks. Moreover, an in vitro study investigated the effects of imeglimin on palmitic acid (PA)-stimulated lipid accumulation, apoptosis, and mitochondrial dysfunction in human hepatocytes. CDA-HFD-fed mice showed hepatic steatosis, inflammation, and fibrosis without hyperglycemia. Imeglimin reduced hepatic steatosis in response to increased expression of β-oxidation-related markers. Imeglimin reduced reactive oxygen species accumulation and increased mitochondrial biogenesis in CDA-HFD-fed mice. Consequently, imeglimin suppressed hepatocyte apoptosis and decreased macrophage infiltration with reduced proinflammatory cytokine expression, suppressing hepatic fibrosis development. PA-stimulated hepatocytes induced lipogenesis, inflammatory cytokine production, and apoptosis, which were significantly suppressed by imeglimin. In mitochondrial function, imeglimin improved PA-stimulated decrease in mitochondrial membrane potential, mitochondrial complexes activity, oxygen consumption rate, and mitochondrial biogenesis marker expression. In conclusion, imeglimin could contribute to prevention of MASH progression through suppressing de novo lipogenesis and enhancing fatty acid oxidation. Full article

Obesity, a prevalent metabolic disorder in youth, leads to complications and economic strain. Gut dysbiosis significantly contributes to obesity and metabolic issues. Bifidobacterium breve, a probiotic strain, may help regulate gut dysbiosis and benefit obese individuals. However, more research is needed on its effect on serum metabolism. A total of 75 overweight or obese young adults (aged 19–45) participated in the current study, and were randomly divided into probiotic and placebo groups using a random number table. Both groups received dietary guidance and underwent twelve weeks of intervention with either oral Bifidobacterium breve BBr60 (BBr60) or a placebo. After the intervention, collection and analysis of fasting serum samples were conducted using mass spectrometry coupled with liquid chromatography. Analyses of associations were conducted in order to determine the correlations between key serum metabolites and clinical obesity indicators, aiming to understand the influence of BBr60. Due to 10 participants dropping out for personal reasons, the study included 32 and 33 participants in the placebo and the BBr60 groups, respectively. The BBr60 intervention significantly regulated 134 serum metabolites and influenced crucial metabolic pathways in obesity management (p < 0.05), including ascorbate and aldarate metabolism for oxidative stress reduction, cholesterol metabolism for lipid regulation, parathyroid hormone synthesis, secretion and action for the endocrine system, oxidative phosphorylation for enhanced energy efficiency, and glycolysis/gluconeogenesis for glucose metabolism. Analysis showed a positive relationship between fasting blood glucose (FBG), aspartate aminotransferase (AST), total protein (TP), and the content of 5-Methyl DL-glutamate (p < 0.05). Similarly, body mass index (BMI), weight, and body fat percentage (BFP) were positively linked to serum metabolites (1-Hydroxycyclohexyl) acetic acid, and 5-Oxooctanoic acid (p < 0.05). Significant associations of AST levels with key serum metabolites in cholesterol metabolism pathways further suggest BBr60’s potential to improve liver function and overall metabolic health in overweight or obese individuals. These findings support BBr60’s effectiveness in modulating serum metabolic profiles and suggest it may improve liver function and BMI in overweight or obese individuals by regulating key serum metabolites. Full article

Large-scale intensive feeding triggered reduced growth performance and nutritional value. Exogenous probiotics can promote the growth performance and nutritional value of fish through improving the intestinal microbiota. However, detailed research on the correlation between the intestinal microbiota, growth performance, and nutritional value remains to be elucidated. Therefore, we performed metagenomic and metabolomic analysis to investigate the effects of probiotic addition to basal diet (1.0 × 10⁸ CFU/g) (PF) and water (1.0 × 10⁸ CFU/g) (PW) on the growth performance, muscle nutritional value, intestinal microbiota and their metabolites, and glucolipid metabolism in Coilia nasus. The results showed that FBW, BL, and SGR were enhanced in PF and PW groups. The concentrations of EAAs, TAAs, SFAs, MUFAs, and PUFAs were increased in PF and PW groups. Metagenomic and metabolic analyses revealed that bacterial community structure and metabolism were changed in the PF and PW groups. Moreover, adding probiotics to diet and water increased SCFAs and bile acids in the intestine. The gene expression associated with lipolysis and oxidation (hsl, pparα, cpt1, and acadm) and glycolysis (gck and pfk) was upregulated, while the gene expression associated with lipid synthesis (srebp1, acc, dgat, and elovl6) and gluconeogenesis (g6pca1, g6pca2, and pck) was downregulated in the liver. Correlation analysis displayed that hepatic glucolipid metabolism was regulated through the microbiota–gut–liver axis. Mantel test analysis showed that growth performance and muscle nutritional value were improved by the gut–liver axis. Our findings offered novel insights into the mechanisms that underlie the enhancement of growth performance and nutritional value in C. nasus and other fish by adding probiotics. Full article