1.The Role and Regulatory Mechanisms of FOXO1 in Hepatic Lipid Deposition
Meng JIA ; Fang-Hui LI ; Shi-Zhan YAN ; Ai-Ju LI ; Yi-Le WANG ; Pin-Shi NI ; Jia-Han HE ; Yin-Lu LI
Progress in Biochemistry and Biophysics 2026;53(4):905-919
Metabolic associated fatty liver disease (MAFLD) is fundamentally driven by an imbalance in hepatic fatty-acid flux: the influx of fatty acids exceeds the liver’s capacity for disposal, resulting in excessive hepatic lipid accumulation, predominantly in the form of triglycerides (TGs). The occurrence and progression of MAFLD depend on disordered regulation across multiple metabolic steps, including fatty-acid uptake, de novo lipogenesis (DNL), fatty-acid oxidation (FAO), and very low-density lipoprotein (VLDL) export. Forkhead box protein O1 (FOXO1) is a key transcriptional regulator within the hepatic network coordinating glucose and lipid metabolism. Under metabolic stress and insulin resistance (IR), FOXO1 expression is frequently increased, whereas its inhibitory phosphorylation is reduced. These changes enhance FOXO1 nuclear localization and transcriptional activity, thereby reprogramming the expression of genes related to metabolism in the liver. Because hepatic lipid deposition is the central pathological feature of MAFLD, the functional status of FOXO1 directly influences hepatic lipid homeostasis. Growing evidence suggests that FOXO1 can exert bidirectional, environment-dependent effects on hepatic lipid accumulation; however, the molecular basis for this functional switch remains incompletely understood. This review systematically summarizes the biological functions and regulatory mechanisms of FOXO1 and its roles in hepatic lipid metabolism, with a particular focus on its crosstalk with insulin signaling. FOXO1 expression is shaped by RNA modifications and epigenetic regulation mediated by non-coding RNAs. Its transcriptional output is precisely governed by post-translational modifications—such as phosphorylation and acetylation—as well as by coordinated nucleocytoplasmic shuttling. Notably, these regulatory patterns vary markedly across nutritional states, degrees of insulin resistance, and stages of disease. In the fed state, insulin/IGF-1 signaling activates the PI3K-AKT pathway, promoting the inhibitory phosphorylation of FOXO1 and facilitating additional modifications, including acetylation, methylation, and ubiquitination. Together, these events drive FOXO1 export from the nucleus and dampen its transcriptional activity, suppressing gluconeogenesis and constraining lipogenic programs. Conversely, during fasting or when insulin signaling is weakened, FOXO1 inhibition is relieved. FOXO1 accumulates in the nucleus, binds to DNA, and regulates the transcription of downstream target genes. Mechanistically, FOXO1 can aggravate hepatic lipid accumulation by activating genes involved in TG synthesis while repressing FAO-related pathways, thereby favoring storage over oxidation. However, under specific conditions, FOXO1 may also alleviate the hepatic lipid burden by promoting TG hydrolysis and enhancing VLDL secretion, thereby reducing the net hepatic lipid load. In addition, lipotoxic signals mediated by ceramides and diacylglycerols (Cer/DAG) activate atypical protein kinase C (aPKC), further exacerbating the disruption of the AKT-FOXO1 axis. This vicious cycle ultimately produces a metabolic paradox in which increased hepatic glucose output coexists with persistent, insulin-independent lipogenesis, accelerating MAFLD progression. Importantly, FOXO1 regulation is not uniform: during early metabolic overload, insulin-mediated suppression may remain effective, whereas in advanced insulin resistance, the loss of AKT control permits sustained FOXO1 activity. Such stage-dependent dynamics may help explain why FOXO1 can either promote steatosis or, in certain contexts, support programs that facilitate lipid turnover. Accordingly, interventions should be liver-specific and tuned to the disease stage, aiming to curb maladaptive FOXO1 signaling while preserving its capacity to promote triglyceride hydrolysis and VLDL secretion when advantageous. Overall, this review offers an important perspective on MAFLD pathogenesis, emphasizing FOXO1 as a potential therapeutic target and providing a theoretical basis for developing liver-specific, disease-course-dependent precision interventions.
2.A systematic review on the integrated application of evidence-based narrative education and undergraduate nursing teaching
Nannan BAI ; Meng LI ; Qian LIANG ; Chou YAO ; Yan WANG ; Ju HAN ; Chenyang HOU ; Nana XING
Chinese Medical Ethics 2026;39(2):229-237
ObjectiveTo systematically evaluate the application of narrative education in undergraduate nursing teaching, to understand the current application status of narrative education, and to provide a theoretical basis for the subsequent establishment of a sound narrative education system. MethodsA systematic search was conducted for studies published in Chinese and English databases on applying narrative education to undergraduate nursing teaching, with the search period ranging from database inception to February 23, 2025. Literature was screened, and relevant information was extracted. A rigorous quality evaluation was conducted on the included studies, and a descriptive analysis was performed on their content. ResultsA total of 20 papers were included, involving 3,180 research subjects, all of whom were undergraduate nursing students. The results of descriptive analysis showed that the teaching model of narrative education primarily encompassed reading narrative works, watching films and videos, performing narrative scenarios, and writing reflective journals. The course setting and content covered pre-teaching preparation and in-teaching implementation. The evaluation of teaching effectiveness included the evaluation of teachers’ teaching methods (student evaluation/self-evaluation) and the evaluation of students’ learning effectiveness (course grade evaluation/humanistic care scale/empathy scale assessment, and others). ConclusionNarrative education combines abstract concepts with concrete clinical situations, which not only enriches students’ learning experiences but also enhances their humanistic literacy. Meanwhile, it provides teachers with opportunities to develop their narrative teaching skills, which requires them to possess profound professional knowledge and employ narrative techniques to guide students in reflection and critical thinking, thereby improving teaching quality and learning outcomes. Future efforts should consistently deepen the connotation research of narrative education and build a systematic nursing education system.
3.Mechanisms of Tongmai Yangxin Pills and Tongxinluo Capsules in Treating Myocardial No-reflow Based on Treating Same Disease with Different Methods
Siqi LIU ; Wenqing YANG ; Ting CHEN ; Yan TANG ; Ju WANG ; Yaxuan PENG ; Haoxue QIN ; Lanyue DENG ; Jialu GONG ; Ning XU ; Shuying ZHANG ; Wei ZHANG ; Ting CHEN
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(17):125-133
ObjectiveTo investigate the mechanisms of Tongmai Yangxin pills (TMYX) and Tongxinluo capsules (TXL) in treating no-reflow (NR) after myocardial ischemia and reperfusion following the concept of treating the same disease with different methods, based on integrative pharmacology and experimental validation. MethodsEighty 8-week-old SPF-grade SD rats were randomly assigned into four groups (n=20): sham operation, NR, TMYX (4 g·kg-1), and TXL (2 mg·kg-1). A rat model of myocardial ischemia-reperfusion no-reflow was established by in-situ ligation of the left anterior descending coronary artery. Gastric gavage was first performed 4 h after the operation, and samples were collected on day 7. Thioflavin S staining was used to observe the NR area in rat myocardium. Echocardiography was performed to examine the cardiac function. Hematoxylin-eosin (HE) staining was conducted to observe the pathological changes of the myocardial tissue. An automatic biochemical analyzer was adopted to measure myocardial enzyme activity. Then, integrated pharmacology was applied for Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Finally, Western blot was employed to quantify the protein levels of key targets in the myocardial tissue, including soluble guanylyl cyclase (sGC), cyclic guanosine monophosphate (cGMP)/dependent protein kinase (PKG), phosphorylated phosphatidylinositol 3-kinase (p-PI3K), phosphorylated protein kinase B (p-Akt), and hypoxia-inducible factor-1α (HIF-1α). ResultsCompared with the sham operation group, the NR group showed increased NR area of myocardium, decreased left ventricular ejection fraction (EF), left ventricular fractional shortening (FS), left ventricular outflow tract peak velocity (LVOT Peak), and left ventricular stroke volume (LVSV) (P<0.01), fractured and disordered myocardial fibers as well as inflammatory cell infiltration in the myocardial tissue, enhanced activities of creatine kinase (CK), creatine kinase isoenzyme (CK-MB), and lactate dehydrogenase (LDH) in the myocardial tissue (P<0.01), and downregulated protein levels of sGC, PKG, phosphorylated (p)-PI3K (Tyr458), and p-Akt (Tyr315) in the myocardial tissue (P<0.05, P<0.01). The expression level of HIF-1α protein showed a downward trend. Compared with the NR group, the TMYX group and TXL group exhibited a decreasing trend in myocardial NR area, EF, FS, and LVOT Peak significantly increased (P<0.05, P<0.01), LVSV showed an upward trend, ameliorated myocardial pathological morphology and inflammatory infiltration, reductions in CK, CK-MB, and LDH activities (P<0.05, P<0.01), and upregulated protein levels of sGC, PKG, p-PI3K (Tyr458) in myocardial tissue (P<0.05, P<0.01), the protein expressions of p-Akt (Tyr315) and HIF-1α showed an upward trend. A comparison of the therapeutic effects between the two compound prescriptions showed that TMYX tended to exert a better effect in restoring cardiac function and protecting cardiac structure in NR rats, whereas TXL was more effective in reducing myocardial NR area and lowering myocardial enzyme activities in NR rats. Integrative pharmacology analysis combined with experimental verification demonstrated that both TMYX and TXL could alleviate NR through the following mechanisms: activating the cyclic cGMP/PKG signaling pathway to regulate vascular tone, activating the PI3K/Akt signaling pathway to dilate blood vessels, and activating the HIF-1 signaling pathway to inhibit oxidative stress. However, TMYX had an advantage in activating the cGMP/PKG pathway, while TXL was superior in activating the PI3K/Akt pathway. The two compound prescriptions exerted comparable effects on the HIF-1 signaling pathway, which might serve as their common therapeutic pathway. ConclusionBoth TMYX and TXL could alleviate NR damage. TMYX exerts its protective effect against NR mainly by activating the cGMP/PKG signaling pathway, while TXL exerts its effect mainly through the PI3K/Akt pathway. The HIF-1α signaling pathway may be a common pathway for the two compound prescriptions to exert their protective effects against NR. This study reveals the similarities and differences between TMYX and TXL in the treatment effect and mechanism for NR, providing an experimental basis and a theoretical basis for better clinical application of the two compound prescriptions.
4.ManNAc improves glucose and lipid metabolic disorders in high-fat diet-induced obese mice
Xiangxue KONG ; Dan LI ; Jiangwei XU ; Ju YANG ; Yingyu WANG ; Jiai YAN ; Jing SUN ; Hong CAO
Chinese Journal of Endocrinology and Metabolism 2025;41(5):401-410
Objective:To investigate the ameliorative effects of N-acetyl-D-mannosamine(ManNAc) on glucose and lipid metabolic disorders in obese mice.Methods:In vivo experiments were conducted using 21 four-week-old C57BL/6JGpt mice, randomly divided into three groups( n=7 per group): a normal control group, a high-fat diet(HFD) control grooup, and a ManNAc treatment group(400 mg·kg -1·d -1). The intervention lasted for 20 weeks. Body weight, food intake, and fasting blood glucose levels were monitored weekly. Glucose tolerance tests(GTT), insulin sensitivity tests(ITT), and respiratory metabolism monitoring were performed in the 17th, 18th, and 19th weeks, respectively. At the end of the experiment, whole-body fat distribution was assessed, and serum lipid profiles were measured. Liver and adipose tissue weights were recorded, and histological analyses including HE staining of liver, adipose and pancreatic tissues were performed. Liver transcriptome sequencing and quantitative real-time PCR(qPCR) were conducted to evaluate hepatic gene expression. In vitro, a hepatic steatosis model was established by inducing HepG2 cell with 0.4 mmol/L oleic acid, followed by treatment with 500 μg/mL ManNAc. Lipid accumulation was assessed using BODIPY staining, and the expression of lipid metabolism-related genes was quantified by qPCR. Results:ManNAc administration attenuated HFD-induced weight gain, reduced total body fat volume, and decreased liver and adipose tissue weights as well as intracellular lipid accumulation. Pancreatic islet numbers increased, while fasting blood glucose levels, glucose tolerance, and insulin sensitivity significantly improved. Serum levels of triglycerides, total cholesterol, and low-density lipoprotein levels were decreased, accompanied by enhanced energy expenditure. Additionally, hepatic expression of Cd36, Fabp3, and Scd1 was downregulated. In vitro, ManNAc significantly reduced lipid accumulation in HepG2 cells and downregulated the expression of Cd36, Fabp3, and Scd1 genes.Conclusion:ManNAc may improve glucose and lipid metabolism by modulating the PPARs-mediated fatty acid metabolic pathway, reducing lipogenesis, promoting fatty acid oxidation and energy expenditure, and enhancing insulin sensitivity, ultimately ameliorating disorders in obese mice.
5.Application research of immersive virtual reality technology in pediatric patients undergoing elective surgery under general anesthesia
Ju ZHANG ; Lili WEI ; Chen XIN ; Jing WANG ; Yan HAN ; Yanyan YANG ; Mengzhu SUN
Chinese Journal of Nursing 2025;60(6):671-676
Objective To explore the application effect of immersive virtual reality(IVR)technology and different viewing content in pediatric patients with general anesthesia during elective surgery,and to provide references for clinical implementation.Methods A total of 180 pediatric patients who underwent elective surgery under general anesthesia in a tertiary hospital in Qingdao from February to October 2023 were selected as study population using convenient sampling method.According to the operation time,60 pediatric patients who underwent surgery from May to July 2023 were included in the immersive panoramic surgical education group,and they could watch the panoramic surgical education video immersively on the basis of routine care.A total of 60 pediatric patients who underwent surgery from August to October 2023 were included in the immersive animation group to watch cartoons immersively on the basis of routine care.A total of 60 pediatric patients who underwent surgery from February to April 2023 were included in the control group and routine preoperative care was implemented.The preoperative anxiety levels,anesthesia induction compliance,and incidence of emergence agitation were compared in the 3 groups by the modified Yale Preoperative Anxiety Scale-Short Form(mYPAS-SF),anesthesia induction cooperation grade,and the Pediatric Anesthesia Emergence Delirium scale(PAED).Results There were statistically significant differences in preoperative anxiety level,anesthesia induced compliance and incidence of emergence agitation during awakening between the 3 groups(P<0.001).Among them,the preoperative anxiety level of the immersive panoramic surgical education group and the immersive animation group was lower than that of the control group,and the difference was statistically significant(P<0.001).The anesthesia induced compliance degree of the immersive panoramic surgical education group and the immersive animation group was better than that of the control group,and the difference was statistically significant(P<0.017),and the incidence of emergence agitation in the immersive panoramic surgical education group was lower than that of the control group,and the difference was statistically significant(P=0.004).Conclusion The use of IVR technology to watch panoramic surgical education videos and cartoons can help reduce the preoperative anxiety level and improve anesthesia induction cooperation degree of pediatric patients with general anesthesia during elective surgery,but the intervention effect of panoramic surgical education videos is better in improving the emergence agitation.
6.Clinical efficacy of the acupuncture method for regulating the intestines and calming the mind in the treatment of autism
Chinese Journal of Primary Medicine and Pharmacy 2025;32(8):1197-1202
Objective:To investigate the clinical efficacy of the acupuncture method for regulating the intestines and calming the mind in the treatment of autism in children.Methods:A total of 120 children with autism who received rehabilitation treatment at Xi'an International Medical Center Hospital from September 2020 to September 2022 were included in this study. They were randomly divided into two groups: the control group ( n = 60), which received only conventional educational rehabilitation training, and the study group ( n = 60), which received acupuncture using the "regulating the intestines and calming the mind" method in conjunction with conventional educational rehabilitation training. The treatment lasted for 6 months. The therapeutic effects were evaluated before and after treatment using the Childhood Autism Rating Scale (CARS), Autism Treatment Evaluation Checklist (ATEC), Autism Behavior Checklist (ABC), and Developmental Quotient (DQ). The scores for CARS, ATEC, ABC, and DQ were compared between the two groups. Results:After treatment, the CARS and ATEC scores for the control group were (33.97 ± 2.41) and (67.87 ± 5.42), respectively, while the scores for the study group were (25.11 ± 2.78) and (41.39 ± 5.74), respectively. The differences between the two groups were statistically significant ( t = 19.27, 20.34, both P = 0.001). After treatment, the ABC score for the study group was (5.23 ± 1.29), which was lower than that for the control group [(11.32 ± 1.63), t = 23.16, P = 0.001]. The DQ score for the study group was (27.90 ± 1.95), which was higher than that for the control group [(24.80 ± 1.75), t = 9.17, P = 0.001]. The overall effective rate in the study group [98.30% (59/60)] was significantly higher than that in the control group [85.00% (51/60), χ2 = 4.89, P = 0.021]. Conclusions:The combination of acupuncture using the "regulating the intestines and calming the mind" method with conventional educational rehabilitation training can effectively improve the clinical symptoms of children with autism, promote the recovery of their self-care abilities and language functions, and demonstrate considerable clinical efficacy.
7.Safety experiment of Ginkgo Leaf Extract and Dipyridamole Injection
Zhaoyun LIU ; Xiaojun LÜ ; Sen WU ; Ju ZHANG ; Pinghui WANG ; Yan LI ; Xiaoling XU ; Jiate SHEN ; Kaiyong HE
Drug Standards of China 2025;26(2):203-212
Objective:To explore the improvement of the quality standard of Ginkgo Leaf Extract and Dipyridamole Injection and conduct safety tests including abnormal toxicity test,allergic reaction test,hemolysis and coagulation test.Methods:Ginkgo Leaf Extract and Dipyridamole Injection from 3 different manufactures(A,B and C)were tested respectively through abnormal toxicity test and acute toxicity test in mice,active systemic anaphylaxis test in guinea pigs and hemolysis test in vitro.Five mice were used in each batch for abnormal toxicity test according to the abnormal toxicity test method in general notice of the Chinese Pharmacopoeia 2020 Volume Ⅳ(1141),and 50 mice were selected in each batch for acute toxicity test to determine the median lethal dose(LD50)or maximum tol-erable dose(MTD)of Ginkgo Leaf Extract and Dipyridamole Injection,which were used to establish the method of abnormal toxicity experiment.The anaphylaxis of Ginkgo Leaf Extract and Dipyridamole Injection was evaluated by active systemic anaphylaxis test in guinea pigs,which was used to establish the method of allergic test.The hemoly-sis test of Ginkgo Leaf Extract and Dipyridamole Injection was studied by conventional tube method in vitro(macro-scopic observation)and improved hemolysis method in vitro(spectrophotometric method),which were used to establish the method of hemolysis and coagulation test.Results:① In manufacture A,the results of abnormal toxicity test were showed that LD50 was20.8 mL·kg-1and MTD was 16.5 mL·kg-1.No death or abnormal reac-tions were observed in mice tested for abnormal toxicity of 2 manufactures(B and C),and MTD was 50 and 40 mL·kg-1,respectively.②The no-observed-adverse-effect dose of Ginkgo Leaf Extract and Dipyridamole Injec-tion from 3 manufactures to guinea pig intravenous was 0.83 mL·kg-1,and no allergic reaction symptoms were observed when Ginkgo Leaf Extract and Dipyridamole Injection was diluted 4 times to challenge the sensitized guinea pigs(equivalent to human clinical dosage).③Differences were observed in the hemolytic effects of Ginkgo Leaf Extract and Dipyridamole Injection from 3 manufactures,but no obvious hemolytic reaction occurred when it was diluted 1.2 times(equivalent to 5%of the maximum clinical concentration).Conclusion:It is recommended to add abnormal toxicity test,allergic reaction test,hemolysis and coagulation test in the quality standard of Ginkgo Leaf Extract and Dipyridamole Injection as safety test items to control the risk.The proposed method is diluting Ginkgo Leaf Extract and Dipyridamole Injection by 5 times,4 times and 1.2 times to perform abnormal toxicity test,allergic reaction test,hemolysis test and coagulation test respectively.
8.Fabrication of Zirconium Dioxide-doped Polydopamine Nanocomposite Coating for Highly Efficient Solid Phase Microextraction of Polycyclic Aromatic Hydrocarbons in Environmental Water Samples
Xiao-Yan SHEN ; Hui-Ju WANG ; Liu HAN ; Zhen MA
Chinese Journal of Analytical Chemistry 2025;53(1):143-151
Zirconium dioxide(ZrO2)is a suitable solid phase microextraction(SPME)fiber coating due to its high thermal and chemical stability and excellent adsorption.Similarly,polydopamine(PDA)can also be utilized as SPME fiber coating because of its strong oxidation resistance and stability,desired adsorption as well as environmental friendliness.In this work,a novel zirconium dioxide-doped polydopamine(ZrO2@PDA)SPME fiber coating was quickly fabricated on the stainless steel(SS)by cyclic voltammetry(CV)using the etched SS wire as working electrode,a Pt rod as counter electrode and a saturated calomel electrode as reference electrode.Coupled with high performance liquid chromatography-ultraviolet detection(HPLC-UV),the extraction performance of the fabricated SS@ZrO2@PDA fiber was evaluated using typical aromatic compounds of polycyclic aromatic hydrocarbons(PAHs),ultraviolet filters(UvFs),phthalate acid esters(PAEs)and chlorophenols(CPs).The SS@ZrO2@PDA fiber showed excellent extraction capability for PAHs and PAEs,however,poor extraction capability for UvFs and no extraction capability for CPs.Therefore,PAHs were selected as target analytes and the key experimental factors on extraction efficiency were optimized.Under the optimized conditions,good linearity was obtained for the developed SPME-HPLC-UV method with the SS@ZrO2@PDA fiber.The limits of detection(LODs,S/N=3)were 0.018-0.082 μg/L.The developed method was successfully applied to determination of trace PAHs in different actual water samples with recoveries of 86.7%-102.4%and RSDs less than 8.2%.In addition,the fabricated novel fiber was simple to prepare and exhibited high stability,good reproducibility and long service life.
9.Detection of virulence genes of Klebsiella pneumoniae and diagnostic efficacy of peg-344
Wenshuo YANG ; Leyang JU ; Diandian CHEN ; Yan WANG ; Peichang WANG ; Jingrong CAO
International Journal of Laboratory Medicine 2025;46(7):769-772,779
Objective To investigate the distribution of virulence genes of Klebsiella pneumoniae(KPN)and to evaluate the diagnostic efficacy of peg-344 for hypervirulent strains.Methods KPN isolates were col-lected from January to December in 2023 in Xuanwu Hospital,Capital Medical University.Whonet5.6 was used to analyze the distribution and drug resistance of bacterial strains.Toxicity testing included wire string test,PCR amplification of virulence genes(peg-344,rmpA,iutA,iroB),K1 and K2 capsule serotypes,serum resistance test,and diagnostic efficacy of detection was analyzed by using receiver operating characteristic curve.Results A total of 122 KPN isolates were collected,including 45(36.9%)sensitive strains,20(16.4%)extended-spectrum β-lactamase positive strains,and 57(46.7%)carbapenem-resistant Klebsiella pneumoniae strains.The specimens were mainly isolated from sputum,urine,and blood,and mainly came from Department of Urology,Department of Neurology,Intensive Care Unit,and Department of Neurosurgery.The positive rate of string test was 27.9%.PCR detected K1(12.3%),K2(8.2%),peg-344(62.3%),rmpA(60.7%),and iutA(73.8%),but the iroB result was negative,and strains with multiple virulence genes accounted for 63.1%.The results of the serum resistance test showed that 43.5%,31.1%,and 25.4%of the samples were at levels 1-2,3-4,and 5-6,respectively.peg-344 had the largest area under the curve for diagnosing the hy-pervirulent strains,followed by peg-344+iutA and peg-344+rmpA.Conclusion KPN is widely distributed in the hospital,and there are a variety of virulence genes.peg-344 has clinical value in distinguishing low viru-lence from high virulence in KPN.
10.ManNAc improves glucose and lipid metabolic disorders in high-fat diet-induced obese mice
Xiangxue KONG ; Dan LI ; Jiangwei XU ; Ju YANG ; Yingyu WANG ; Jiai YAN ; Jing SUN ; Hong CAO
Chinese Journal of Endocrinology and Metabolism 2025;41(5):401-410
Objective:To investigate the ameliorative effects of N-acetyl-D-mannosamine(ManNAc) on glucose and lipid metabolic disorders in obese mice.Methods:In vivo experiments were conducted using 21 four-week-old C57BL/6JGpt mice, randomly divided into three groups( n=7 per group): a normal control group, a high-fat diet(HFD) control grooup, and a ManNAc treatment group(400 mg·kg -1·d -1). The intervention lasted for 20 weeks. Body weight, food intake, and fasting blood glucose levels were monitored weekly. Glucose tolerance tests(GTT), insulin sensitivity tests(ITT), and respiratory metabolism monitoring were performed in the 17th, 18th, and 19th weeks, respectively. At the end of the experiment, whole-body fat distribution was assessed, and serum lipid profiles were measured. Liver and adipose tissue weights were recorded, and histological analyses including HE staining of liver, adipose and pancreatic tissues were performed. Liver transcriptome sequencing and quantitative real-time PCR(qPCR) were conducted to evaluate hepatic gene expression. In vitro, a hepatic steatosis model was established by inducing HepG2 cell with 0.4 mmol/L oleic acid, followed by treatment with 500 μg/mL ManNAc. Lipid accumulation was assessed using BODIPY staining, and the expression of lipid metabolism-related genes was quantified by qPCR. Results:ManNAc administration attenuated HFD-induced weight gain, reduced total body fat volume, and decreased liver and adipose tissue weights as well as intracellular lipid accumulation. Pancreatic islet numbers increased, while fasting blood glucose levels, glucose tolerance, and insulin sensitivity significantly improved. Serum levels of triglycerides, total cholesterol, and low-density lipoprotein levels were decreased, accompanied by enhanced energy expenditure. Additionally, hepatic expression of Cd36, Fabp3, and Scd1 was downregulated. In vitro, ManNAc significantly reduced lipid accumulation in HepG2 cells and downregulated the expression of Cd36, Fabp3, and Scd1 genes.Conclusion:ManNAc may improve glucose and lipid metabolism by modulating the PPARs-mediated fatty acid metabolic pathway, reducing lipogenesis, promoting fatty acid oxidation and energy expenditure, and enhancing insulin sensitivity, ultimately ameliorating disorders in obese mice.

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