Search Results (30)

Group A rotavirus continues to be a leading global etiological agent of severe gastroenteritis in young children under 5 years of age. The replication of this virus in the host is associated with the occurrence of Lewis antigens and the secretor condition. Moreover, histo-blood group antigens (HBGAs) act as attachment factors to the outer viral protein of VP4 for rotavirus. Therefore, in this study, we employed a metabolomic approach to reveal potential signature metabolic molecules and metabolic pathways specific to rotavirus P[8] strain infection (VP4 genotype), which is associated with the expression of HBGA combined secretor and Lewis (Le) phenotypes, specifically secretor/Le^(a+b+). Further integration of the achieved metabolomics results with lipidomic and proteomics metadata analyses was performed. Saliva samples were collected from children diagnosed as negative or positive for rotavirus P[8] strain infection (VP4 genotype), which is associated with the HBGA combined secretor/Le^(a+b+). A total of 22 signature metabolic molecules that were downregulated include butyrate, putrescine, lactic acid, and 7 analytes. The upregulated metabolic molecule was 2,3-Butanediol. Significant pathway alterations were also specifically observed in various metabolism processes, including galactose and butanoate metabolisms. Butyrate played a significant role in viral infection and was revealed to exhibit different reactions with glycerolipids, glycerophospholipids, sphingolipids, sterol lipids, and fatty acyls. Moreover, butyrate might interact with protein receptors of free fatty acid receptor 2 (FFAR2) and free fatty acid receptor 3 (FFAR3). The revealed metabolic pathways and molecule might provide fundamental insight into the status of rotavirus P[8] strain infection for monitoring its effects on humans. Full article

(1) Background: Hepatic lipid accumulation is the initial factor in metabolic-associated fatty liver disease (MAFLD) in type 2 diabetics, leading to accelerated liver damage. The NOD-like receptor protein 3 (NLRP3) inflammasome plays a critical role in this process. Dapansutrile (DAPA) is a novel NLRP3 inflammasome inhibitor; however, its effect on ectopic lipid accumulation in the liver remains unclear. This study aimed to investigate the therapeutic effect of DAPA on hepatic lipid accumulation in a diabetic mouse model and its potential mechanisms. (2) Methods: The effects of DAPA on hepatic ectopic lipid deposition and liver function under metabolic stress were evaluated in vivo using db/db and high-fat diet (HFD) + streptozotocin (STZ) mouse models. Additionally, the role and mechanism of DAPA in cellular lipid deposition, mitochondrial oxidative stress, and inflammation were assessed in HepG2 cells treated with free fatty acids (FFA) and DAPA. (3) Results: Our findings indicated that DAPA treatment improved glucose and lipid metabolism in diabetic mice, particularly addressing liver heterotopic lipid deposition and insulin resistance. DAPA treatment also ameliorated lipid accumulation and mitochondrial-related functions and inflammation in HepG2 cells through the NLRP3-Caspase-1 signaling axis. (4) Conclusions: Targeting NLRP3 with DAPA may represent a novel therapeutic approach for diabetes-related fatty liver diseases. Full article

This study tested the ISL against renal damage induced by a high-fat diet (HFD) and explored its underlying mechanisms. Adult male rats were assigned to four groups: (1) control on a standard diet (STD), (2) ISL on STD (30 mg/kg), (3) HFD, and (4) HFD + ISL (30 mg/kg). After 12 weeks of dietary intervention, ISL treatment led to significant reductions in body weight gain, visceral fat, and glucose and insulin levels in HFD-fed rats. Notably, ISL decreased serum urea and creatinine, increased serum albumin, and improved urinary profiles by lowering the urinary albumin and the albumin/creatinine ratio. Histological analyses revealed that ISL enhanced the glomerular structure and mitigated tubular damage, as evidenced by reduced urinary excretion of the kidney injury markers NGAL and KIM-1. Additionally, ISL significantly lowered cholesterol, triglycerides, and free fatty acids in both the control and HFD groups while also decreasing oxidized low-density lipoproteins (ox-LDLs) and malondialdehyde (MDA). Importantly, ISL enhanced renal antioxidant levels, increasing glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT). Moreover, ISL downregulated mRNA levels of MD-2, Toll-like receptor-4 (TLR-4), and NF-κB, leading to reduced NF-κB p65 levels in renal tissues. In conclusion, ISL offers substantial protection against HFD-induced renal toxicity through mechanisms that attenuate metabolic stress, enhance antioxidant defenses, and inhibit the MD-2/TLR4/NF-κB inflammatory pathway. Full article

We planned to explore the protective activities of extract of Phyllanthus emblica L. (EPE) on insulin resistance and metabolic disorders including hyperlipidemia, visceral obesity, and renal dysfunction in high-fat diet (HFD)-progressed T2DM mice. Mice treatments included 7 weeks of HFD induction followed by EPE, fenofibrate (Feno), or metformin (Metf) treatment daily for another 4-week HFD in HFD-fed mice. Finally, we harvested blood to analyze some tests on circulating glycemia and blood lipid levels. Western blotting analysis was performed on target gene expressions in peripheral tissues. The present findings indicated that EPE treatment reversed the HFD-induced increases in blood glucose, glycosylated HbA1_C, and insulin levels. Our findings proved that treatment with EPE in HFD mice effectively controls hyperglycemia and hyperinsulinemia. Our results showed that EPE reduced blood lipid levels, including a reduction in blood triglyceride (TG), total cholesterol (TC), and free fatty acid (FFA); moreover, EPE reduced blood leptin levels and enhanced adiponectin concentrations. EPE treatment in HFD mice reduced BUN and creatinine in both blood and urine and lowered albumin levels in urine; moreover, EPE decreased circulating concentrations of inflammatory NLR family pyrin domain containing 3 (NLRP3) and kidney injury molecule-1 (KIM-1). These results indicated that EPE displayed antihyperglycemic and antihyperlipidemic activities but alleviated renal dysfunction in HFD mice. The histology examinations indicated that EPE treatment decreased adipose hypertrophy and hepatic ballooning, thus contributing to amelioration of lipid accumulation. EPE treatment decreased visceral fat amounts and led to improved systemic insulin resistance. For target gene expression levels, EPE enhanced AMP-activated protein kinase (AMPK) phosphorylation expressions both in livers and skeletal muscles and elevated the muscular membrane glucose transporter 4 (GLUT4) expressions. Treatment with EPE reduced hepatic glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (PEPCK) expressions to suppress glucose production in the livers and decreased phosphorylation of glycogen synthase kinase 3β (GSK3β) expressions to affect hepatic glycogen synthesis, thus convergently contributing to an antidiabetic effect and improving insulin resistance. The mechanism of the antihyperlipidemic activity of EPE involved a decrease in the hepatic phosphorylation of mammalian target of rapamycin complex C1 (mTORC1) and p70 S6 kinase 1 (S6K1) expressions to improve insulin resistance but also a reduction in hepatic sterol regulatory element binding protein (SREBP)-1c expressions, and suppression of ACC activity, thus resulting in the decreased fatty acid synthesis but elevated hepatic peroxisome proliferator-activated receptor (PPAR) α and SREBP-2 expressions, resulting in lowering TG and TC concentrations. Our results demonstrated that EPE improves insulin resistance and ameliorates hyperlipidemia in HFD mice. Full article

Short-chain fatty acids (SCFAs) are the major microbial metabolites produced from the fermentation of dietary fiber in the gut. They are recognised as secretagogues of the glucagon-like peptides, GLP-1 and GLP-2, likely mediated by the activation of free fatty acid receptors 2 and 3 (FFAR2 and 3) expressed on enteroendocrine L-cells. Fiber-deficient diets are associated with decreased intestinal function and decreased colonic GLP-1 and GLP-2 content. Here, we speculated that the lowered colonic GLP-1 observed following a fiber-free diet was a consequence of decreased SCFA production and a subsequent decrease in FFAR2/3 activation. Furthermore, we explored the consequences of a fiber-free diet followed by intestinal injury, and we mechanistically explored the SCFA-FFAR2/3-GLP-1 pathway to explain the increased severity. Colonic luminal content from mice fed either a fiber-free or chow diet were analysed for SCFA content by LC–MS. FFAR2/3 receptor contributions to SCFA-mediated colonic GLP-1 secretion were assessed in isolated perfused preparations of the colon from FFAR2/3 double knockout (KO) and wild-type (WT) mice. Colitis was induced by the delivery of 3% dextran sulfate sodium (DSS) for 4 days in the drinking water of mice exposed to a fiber-free diet for 21 days. Colitis was induced by the delivery of 3% DSS for 7 days in FFAR2/3 KO mice. The removal of dietary fiber significantly decreased SCFA concentrations in the luminal contents of fiber-free fed mice compared to chow-fed mice. In the perfused colon, luminal SCFAs significantly increased colonic GLP-1 secretion in WT mice but not in FFAR2/3 KO mice. In the DSS-induced colitis model, the removal of dietary fiber increased the severity and prevented the recovery from intestinal injury. Additionally, colitis severity was similar in FFAR2/3 KO and WT mice after DSS application. In conclusion, the results confirm that the removal of dietary fiber is sufficient to decrease the colonic concentrations of SCFAs. Additionally, we show that a fiber-free diet predisposes the colon to increased intestinal injury, but this effect is independent of FFAR2 and FFAR3 signalling; therefore, it is unlikely that a fiber-free diet induces a decrease in luminal SCFAs and sensitivity to intestinal disease involves the SCFA-FFAR2/3-GLP-1 pathway. Full article

Supplementation with fish oil rich in omega-3 polyunsaturated fatty acids (n-3 PUFAs) effectively reduces acute and chronic alcohol-induced hepatic steatosis. We aimed to find molecular mechanisms underlying the effects of n-3 PUFAs in alcohol-induced hepatic steatosis. Because free fatty acid receptor 4 (FFA4, also known as GPR120) has been found as a receptor for n-3 PUFAs in an ethanol-induced liver steatosis model, we investigated whether n-3 PUFAs protect against liver steatosis via FFA4 using AH7614, an FFA4 antagonist, and Ffa4 knockout (KO) mice. N-3 PUFAs and compound A (CpdA), a selective FFA4 agonist, reduced the ethanol-induced increase in lipid accumulation in hepatocytes, triglyceride content, and serum ALT levels, which were not observed in Ffa4 KO mice. N-3 PUFAs and CpdA also reduced the ethanol-induced increase in lipogenic sterol regulatory element-binding protein-1c expression in an FFA4-dependent manner. In Kupffer cells, treatment with n-3 PUFA and CpdA reversed the ethanol-induced increase in tumor necrosis factor-α, cyclooxygenase-2, and NLR family pyrin domain-containing 3 expression levels in an FFA4-dependent manner. In summary, n-3 PUFAs protect against ethanol-induced hepatic steatosis via the anti-inflammatory actions of FFA4 on Kupffer cells. Our findings suggest FFA4 as a therapeutic target for alcoholic hepatic steatosis. Full article

With the increasing prevalence of sleep deprivation (SD)-related disorders, the effective treatment of sleep disorders has become a critical health research topic. Thus, we hypothesized and investigated the effectiveness of a 3-week melatonin intervention on neuropsychiatric behavioral responses mediated throughout melatonin receptors, gut microbiota, and lipid metabolites in rats with chronic SD. Eighteen 6-week-old Wistar rats were used and divided into the control grup (C, n = 6), SD group (n = 6), and melatonin-supplemented group (SDM, n = 6). During weeks 0 to 6, animals were provided with the AIN-93M diet and free access to water. Four-week chronic SD was conducted from weeks 7 to 10. Exogenous melatonin administration (10 mg/kg BW) was injected intraperitoneally 1 h before the daily administration of SD for 3 weeks in the SDM group. SD rats exhibited anxiety-like behavior, depression-like behavior, and cognitive impairment. Exogenous melatonin administration ameliorated neuropsychiatric behaviors induced by chronic SD. Analysis of fecal metabolites indicated that melatonin may influence brain messaging through the microbiota–gut–brain axis by increasing the production of short-chain fatty acids (SCFA) and decreasing the production of secondary bile acids (SBA). Four-week SD reduced the cerebral cortex expression of MT1, but not in the colon. Chronic SD led to anxiety and depression-like behaviors and cognitive decline, as well as the reduced intestinal level of SCFAs and the enhanced intestinal level of SBAs in rats. In this work, we confirmed our hypothesis that a 3-week melatonin intervention on neuropsychiatric behavioral response mediated throughout melatonin receptors, gut microbiota, and lipid metabolites in rats with chronic SD. Full article

This study examined the preventative effects of esculeogenin A (ESGA), a newly discovered glycan from tomato, on liver damage and hepatic steatosis in high-fat-diet (HFD)-fed male rats. The animals were divided into six groups (each of eight rats): a control group fed a normal diet, control + ESGA (200 mg/kg), HFD, and HFD + ESAG in 3 doses (50, 100, and 200 mg/kg). Feeding and treatments were conducted for 12 weeks. Treatment with ESGA did not affect gains in the body or fat weight nor increases in fasting glucose, insulin, and HOMA-IR or serum levels of free fatty acids (FFAs), tumor-necrosis factor-α, and interleukin-6 (IL-6). On the contrary, it significantly reduced the serum levels of gamma-glutamyl transpeptidase (GGT), aspartate aminotransferase (AST), alanine aminotransferase (ALT), total triglycerides (TGs), cholesterol (CHOL), and low-density lipoprotein cholesterol (LDL-c) in the HFD-fed rats. In addition, it improved the liver structure, attenuating the increase in fat vacuoles; reduced levels of TGs and CHOL, and the mRNA levels of SREBP1 and acetyl CoA carboxylase (ACC); and upregulated the mRNA levels of proliferator-activated receptor α (PPARα) and carnitine palmitoyltransferase I (CPT I) in HFD-fed rats. These effects were concomitant with increases in the mRNA, cytoplasmic, and nuclear levels of nuclear factor erythroid 2-related factor 2 (Nrf2), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and heme oxygenase-1 (HO); a reduction in the nuclear activity of nuclear factor-kappa beta (NF-κB); and inhibition of the activity of nuclear factor kappa B kinase subunit beta (IKKβ). All of these effects were dose-dependent effects in which a normal liver structure and normal levels of all measured parameters were seen in HFD + ESGA (200 mg/kg)-treated rats. In conclusion, ESGA prevents NAFLD in HFD-fed rats by attenuating hyperlipidemia, hepatic steatosis, oxidative stress, and inflammation by acting locally on Nrf2, NF-κB, SREBP1, and PPARα transcription factors. Full article

The enteric nervous system is affected by inflammatory bowel diseases (IBD). Gut microbiota ferments dietary fibers and produces short-chain fatty acids, such as Butyrate, which bind to G protein–coupled receptors, such as GPR41, and contribute to maintaining intestinal health. This work aimed to study the GPR41 in myenteric neurons and analyze the effect of Butyrate in mice submitted to experimental ulcerative colitis. The 2, 4, 6 trinitrobenzene sulfonic acid (TNBS) was injected intrarectally in C57BL/6 mice (Colitis). Sham group received ethanol (vehicle). One group was treated with 100 mg/kg of Sodium Butyrate (Butyrate), and the other groups received saline. Animals were euthanized 7 days after colitis induction. Analyzes demonstrated colocalization of GPR41 with neurons immunoreactive (-ir) to nNOS and ChAT-ir and absence of colocalization of the GPR41 with GFAP-ir glia. Quantitative results demonstrated losses of nNOS-ir, ChAT-ir, and GPR41-ir neurons in the Colitis group and Butyrate treatment attenuated neuronal loss. The number of GFAP-ir glia increased in the Colitis group, whereas Butyrate reduced the number of these cells. In addition, morphological alterations observed in the Colitis group were attenuated in the Butyrate group. The presence of GPR41 in myenteric neurons was identified, and the treatment with Butyrate attenuated the damage caused by experimental ulcerative colitis. Full article

The association between oral microbiota and cancer development has been a topic of intense research in recent years, with compelling evidence suggesting that the oral microbiome may play a significant role in cancer initiation and progression. However, the causal connections between the two remain a subject of debate, and the underlying mechanisms are not fully understood. In this case–control study, we aimed to identify common oral microbiota associated with several cancer types and investigate the potential mechanisms that may trigger immune responses and initiate cancer upon cytokine secretion. Saliva and blood samples were collected from 309 adult cancer patients and 745 healthy controls to analyze the oral microbiome and the mechanisms involved in cancer initiation. Machine learning techniques revealed that six bacterial genera were associated with cancer. The abundance of Leuconostoc, Streptococcus, Abiotrophia, and Prevotella was reduced in the cancer group, while abundance of Haemophilus and Neisseria enhanced. G protein-coupled receptor kinase, H+-transporting ATPase, and futalosine hydrolase were found significantly enriched in the cancer group. Total short-chain fatty acid (SCFAs) concentrations and free fatty acid receptor 2 (FFAR2) expression levels were greater in the control group when compared with the cancer group, while serum tumor necrosis factor alpha induced protein 8 (TNFAIP8), interleukin-6 (IL6), and signal transducer and activator of transcription 3 (STAT3) levels were higher in the cancer group when compared with the control group. These results suggested that the alterations in the composition of oral microbiota can contribute to a reduction in SCFAs and FFAR2 expression that may initiate an inflammatory response through the upregulation of TNFAIP8 and the IL-6/STAT3 pathway, which could ultimately increase the risk of cancer onset. Full article

There is growing evidence that gut microbiota dysbiosis is linked to the etiopathogenesis of nonalcoholic fatty liver disease (NAFLD), from the initial stage of disease until the progressive stage of nonalcoholic steatohepatitis (NASH) and the final stage of cirrhosis. Conversely, probiotics, prebiotics, and synbiotics have shown promise in restoring dysbiosis and lowering clinical indicators of disease in a number of both preclinical and clinical studies. Additionally, postbiotics and parabiotics have recently garnered some attention. The purpose of this bibliometric analysis is to assess recent publishing trends concerning the role of the gut microbiome in the progression of NAFLD, NASH and cirrhosis and its connection with biotics. The free access version of the Dimensions scientific research database was used to find publications in this field from 2002 to 2022. VOSviewer and Dimensions’ integrated tools were used to analyze current research trends. Research into the following topics is expected to emerge in this field: (1) evaluation of risk factors which are correlated with the progression of NAFLD, such as obesity and metabolic syndrome; (2) pathogenic mechanisms, such as liver inflammation through toll-like receptors activation, or alteration of short-chain fatty acids metabolisms, which contribute to NAFLD development and its progression in more severe forms, such as cirrhosis; (3) therapy for cirrhosis through dysbiosis reduction, and research on hepatic encephalopathy a common consequence of cirrhosis; (4) evaluation of diversity, and composition of gut microbiome under NAFLD, and as it varies under NASH and cirrhosis by rRNA gene sequencing, a tool which can also be used for the development of new probiotics and explore into the impact of biotics on the gut microbiome; (5) treatments to reduce dysbiosis with new probiotics, such as Akkermansia, or with fecal microbiome transplantation. Full article

db/db mice, which lack leptin receptors and exhibit hyperphagia, show disturbances in energy metabolism and are a model of obesity and type 2 diabetes. The geroneuroprotector drug candidate CMS121 has been shown to be effective in animal models of Alzheimer’s disease and aging through the modulation of metabolism. Thus, the hypothesis was that CMS121 could protect db/db mice from metabolic defects and thereby reduce liver inflammation and kidney damage. The mice were treated with CMS121 in their diet for 6 months. No changes were observed in food and oxygen consumption, body mass, or locomotor activity compared to control db/db mice, but a 5% reduction in body weight was noted. Improved glucose tolerance and reduced HbA1c and insulin levels were also seen. Blood and liver triglycerides and free fatty acids decreased. Improved metabolism was supported by lower levels of fatty acid metabolites in the urine. Markers of liver inflammation, including NF-κB, IL-18, caspase 3, and C reactive protein, were lowered by the CMS121 treatment. Urine markers of kidney damage were improved, as evidenced by lower urinary levels of NGAL, clusterin, and albumin. Urine metabolomics studies provided further evidence for kidney protection. Mitochondrial protein markers were elevated in db/db mice, but CMS121 restored the renal levels of NDUFB8, UQCRC2, and VDAC. Overall, long-term CMS121 treatment alleviated metabolic imbalances, liver inflammation, and reduced markers of kidney damage. Thus, this study provides promising evidence for the potential therapeutic use of CMS121 in treating metabolic disorders. Full article

A mechanistic understanding of the dynamic interactions between the mitochondria and the gut microbiome is thought to offer innovative explanations for many diseases and thus provide innovative management approaches, especially in GIT-related autoimmune diseases, such as ulcerative colitis (UC). β-Glucans, important components of many nutritious diets, including oats and mushrooms, have been shown to exhibit a variety of biological anti-inflammatory and immune-modulating actions. Our research study sought to provide insight into the function of β-glucan and/or fidarestat in modifying the microbiome/mitochondrial gut axis in the treatment of UC. A total of 50 Wistar albino male rats were grouped into five groups: control, UC, β-Glucan, Fidarestat, and combined treatment groups. All the groups were tested for the presence of free fatty acid receptors 2 and 3 (FFAR-2 and -3) and mitochondrial transcription factor A (TFAM) mRNA gene expressions. The reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and ATP content were found. The trimethylamine N-oxide (TMAO) and short-chain fatty acid (SCFA) levels were also examined. Nuclear factor kappa β (NF-kβ), nuclear factor (erythroid-2)-related factor 2 (Nrf2) DNA binding activity, and peroxisome proliferator-activated receptor gamma co-activator-1 (PGC-1) were identified using the ELISA method. We observed a substantial increase FFAR-2, -3, and TFAM mRNA expression after the therapy. Similar increases were seen in the ATP levels, MMP, SCFA, PGC-1, and Nrf2 DNA binding activity. The levels of ROS, TMAO, and NF-kβ, on the other hand, significantly decreased. Using β-glucan and fidarestat together had unique therapeutic benefits in treating UC by focusing on the microbiota/mitochondrial axis, opening up a new avenue for a potential treatment for such a complex, multidimensional illness. Full article

Lipophagy, a type of autophagy that breaks down lipid droplets, is essential in the regulation of intracellular lipid accumulation and intracellular free fatty acid levels in numerous organisms and metabolic conditions. We investigated the effects of Stevia rebaudiana Bertoni (S), a low-calorie sweetener, and stevioside (SS) on hepatic steatosis and autophagy in hepatocytes, as well as in db/db mice. S and SS reduced the body and liver weight and levels of serum triglyceride, total cholesterol, and hepatic lipogenic proteins. In addition, S and SS increased the levels of fatty acid oxidase, peroxisome proliferator-activated receptor alpha (PPARα), and microtubule-associated protein light chain 3 B but decreased that of sequestosome 1 (p62) in the liver of db/db mice. Additionally, Beclin 1, lysosomal associated membrane protein 1, and phosphorylated adenosine monophosphate-activated protein kinase protein expression was augmented following S and SS treatment of db/db mice. Furthermore, the knockdown of PPARα blocked lipophagy in response to SS treatment in HepG2 cells. These outcomes indicate that PPARα-dependent lipophagy is involved in hepatic steatosis in the db/db mouse model and that SS, a PPARα agonist, represents a new therapeutic option for managing associated diseases. Full article

The objective of this study was to investigate and compare fatty acids and metabolites in the longissimus dorsi muscle between Black Tibetan and Chaka sheep grazing in a highly saline environment. A total of eight castrated sheep (14 months old) with similar body weights (25 ± 2.2 kg) were selected. The experimental treatments included Black Tibetan (BT) and Chaka sheep (CK) groups, and each group had four replications. The experiment lasted for 20 months. All sheep grazed in a highly saline environment for the whole experimental period and had free access to water. The results showed that the diameter (42.23 vs. 51.46 $\mathsf{\mu }$m), perimeter (131.78 vs. 166.14 $\mathsf{\mu }$m), and area of muscle fibers (1328.74 vs. 1998.64 $\mathsf{\mu }$m²) were smaller in Chaka sheep than in Black Tibetan sheep. The ash content in the longissimus dorsi was lower in Chaka sheep than in Black Tibetan sheep (p = 0.010), and the contents of dry matter (DM), ether extract (EE), and crude protein (CP) in the longissimus dorsi showed no differences (p > 0.05). For fatty acids, the proportions of C10:0, C15:0, and tC18:1 in the longissimus dorsi were higher in Chaka sheep than in Black Tibetan sheep (p < 0.05). However, all other individual fatty acids were similar among treatments, including saturated fatty acids (SFAs), unsaturated fatty acids (UFAs), monounsaturated fatty acids (MUFAs), polyunsaturated fatty acids (PUFAs), and the ratios of n-6 PUFAs to n-3 PUFAs and PUFAs to SFAs (p > 0.05). A total of 65 biomarkers were identified between the two breeds of sheep. Among these metabolites, 40 metabolic biomarkers were upregulated in the CK group compared to the BT group, and 25 metabolites were downregulated. The main metabolites include 30 organic acids, 9 amino acids, 5 peptides, 4 amides, 3 adenosines, 2 amines, and other compounds. Based on KEGG analysis, eight pathways, namely, fatty acid biosynthesis, purine metabolism, the biosynthesis of unsaturated fatty acids, renin secretion, the regulation of lipolysis in adipocytes, neuroactive ligand–receptor interaction, the cGMP-PKG signaling pathway, and the cAMP signaling pathway, were identified as significantly different pathways. According to the results on fatty acids and metabolites, upregulated organic acid and fatty acid biosynthesis increased the meat quality of Chaka sheep. Full article