Journal of Neuroinflammation
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2023
·Vol. 20
·期 1
·1-18
·
IF 9.3
Yao Ke,Mou Qianxue,Lou Xiaotong,Ye Meng,Zhao Bowen,Hu Yuanyuan,Luo Jing,Zhang Hong,Li Xing,Zhao Yin
Background Optic nerve injury (ONI) is a key cause of irreversible blindness and triggers retinal ganglion cells (RGCs) change and synapse loss. Microglia is the resistant immune cell in brain and retina and has been demonstrated to be highly related with neuron and synapse injury. However, the function of Sirtuin 1 (SIRT1), a neuroprotective molecule, in mediating microglial activation, retinal synapse loss and subsequent retinal ganglion cells death in optic nerve injury model as well as the regulatory mechanism remain unclear.MethodTo this end, optic nerve crush (ONC) model was conducted to mimic optic nerve injury. Resveratrol and EX527, highly specific activator and inhibitor of SIRT1, respectively, were used to explore the function of SIRT1 in vivo and vitro. Cx3Cr1-CreERT2/RaptorF/F mice were used to delete Raptor for inhibiting mammalian target of rapamycin complex 1 (mTORC1) activity in microglia. HEK293 and BV2 cells were transfected with plasmids to explore the regulatory mechanism of SIRT1.Results We discovered that microglial activation and synapse loss in retinal inner plexiform layer (IPL) occurred after optic nerve crush, with later-development retinal ganglion cells death. SIRT1 activation induced by resveratrol inhibited microglial activation and attenuated synapse loss and retinal ganglion cells injury. After injury, microglial phagocytosed synapse and SIRT1 inhibited this process to protect synapse and retinal ganglion cells. Moreover, SIRT1 exhibited neuron protective effects via activating tuberous sclerosis complex 2 (TSC2) through deacetylation, and enhancing the inhibition effect of tuberous sclerosis complex 2 on mammalian target of rapamycin complex 1 activity.Conclusion Our research provides novel insights into microglial SIRT1 in optic nerve injury and suggests a potential strategy for neuroprotective treatment of optic nerve injury disease.
研究领域:
神经科学
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眼科学
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分子生物学
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细胞生物学
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PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2025
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IF 5.4
Xiaolong Feng,Xinru Tao,Penghui Li,Jun Chen,Kaiyi Chen,Jinsheng Jiang,Yuan Cai,Yanmei Peng
Ethnopharmacological relevance Yuye Jiedu Granule (YYJD), a traditional herb preparation developed by Hunan Changde Sanjin Pharmaceutical Co., Ltd., has been used in clinical settings for many years to manage upper respiratory tract infections (URTI) attributed to exogenous wind-heat. Although its effectiveness is well recognized, the active constituents responsible for its effects and the molecular pathways involved are not clear yet. Aim of the study To identify the bioactive constituents of YYJD and elucidate its molecular mechanisms in treating URTI. Materials and methods Initially, the chemical composition of YYJD was analyzed using ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS/MS) in combination with a molecular networking approach. Anti-inflammatory components within the formula were then identified using a UPLC-based separation system and a dual-luciferase reporter gene screening assay, followed by in vitro validation. Subsequently, an acute pneumonia model was developed using Pseudomonas aeruginosa infection to comprehensively assess the therapeutic efficacy of YYJD through integrated transcriptomic, metabolomic, and network pharmacology analyses. Finally, the underlying molecular mechanisms were experimentally confirmed. Results A total of 145 chemical constituents were identified in YYJD, among which 15 were found to inhibit NF-κB. In vivo studies demonstrated that YYJD notably decreased mortality, lung indices, and serum pro-inflammatory cytokines in P. aeruginosa -infected mice. Integrated multi-omics analysis highlighted adenosine monophosphate (AMP) as a central metabolite, with major bioactive compounds classified as organic acids, flavonoids, iridoid glycosides, and triterpenoid saponins . Nine pivotal targets and the AMPK-mTORC1/2-PI3K/Akt/NF-κB axis were identified as central to YYJD’s anti-URTI effects. Mechanistically, YYJD modulated the phosphorylation of GSK3β, Akt, IκBα, mTOR, and AMPK, along with the p65 expression. Conclusion This study presents the first in-depth analysis of YYJD’s chemical profile and elucidates its multi-target therapeutic mechanisms against URTI through AMPK-centered metabolic-inflammatory interplay. These results offer a stronger scientific foundation for the clinical use of YYJD and introduce a potential new approach for treating respiratory infections.
研究领域:
免疫学
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呼吸病学
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药理学
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分子生物学
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药物代谢
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转化医学
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感染性疾病
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DOI
PubMed
高影响因子
Molecular Medicine Reports
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2018
·Vol. 18
·期 6
·5445-5454
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IF 1.922
Yang Su,Jingxiao Lu,Pian Gong,Xianguo Chen,Chaozhao Liang,Jie Zhang
Acute kidney injury (AKI) is a clinically common and severe complication of ischemia‑reperfusion (I/R), associated with high morbidity and mortality rates, and prolonged hospitalization. Rapamycin is a type of macrolide, primarily used for anti‑rejection therapy following organ transplantation and the treatment of autoimmune diseases. Rapamycin has been identified to exert a protective effect against AKI induced by renal I/R as an autophagy inducer. However, whether rapamycin preconditioning may relieve AKI following cerebral I/R (CIR) remains to be fully elucidated. The purpose of the present study was to investigate the effects of CIR on the renal system of rats and the role of rapamycin in AKI following CIR. In the present study, a CIR model was established in Sprague‑Dawley rats via a 90‑min period of middle cerebral artery occlusion and 24 h reperfusion, and pretreatment with an intraperitoneal injection of rapamycin (dosage: 1 mg/kg; 0.5 h) prior to CIR. The levels of serum creatinine and blood urea nitrogen (BUN), and the expression of inflammation‑, apoptosis‑ and autophagy‑associated markers were subsequently measured. In addition to certain histopathological alterations to the kidney, it was identified that CIR significantly increased the levels of serum creatinine, BUN, tumor necrosis factor‑α and interleukin‑1β, and significantly induced apoptosis and autophagy. It was observed that rapamycin induced autophagy through the mammalian target of rapamycin complex 1/autophagy‑related 13/unc‑51 like autophagy activating kinase 1 signaling pathway, and that rapamycin pre‑treatment significantly improved renal function and alleviated renal tissue inflammation and cell apoptosis in rats following CIR. In conclusion, the results suggested that rapamycin may alleviate AKI following CIR via the induction of autophagy.
研究领域:
药理学
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肾病学
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神经病学
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细胞生物学
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分子生物学
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PubMed
高影响因子
JOURNAL OF PROTEOME RESEARCH
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2023
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IF 4.4
Mengmeng Zheng,Yanmei Zhang,Yao Xu,Ying Han,Yingli Wu,Jingwu Kang
Salvianolic acid A (SAA), a major active ingredient of Salvia miltiorrhiza Bunge (Danshen), displays strong antiproliferative activity against cancer cells. However, their protein targets remain unknown. Here, we deconvoluted the protein targets of SAA using chemoproteomics and phosphoproteomics. By using alkynylated SAA as a probe, we discovered that SAA is a covalent ligand that can modify cellular proteins via its electrophilic α,β-unsaturated ester moiety. The subsequent chemoproteomics profiling revealed that 46 proteins were covalently modified by SAA, including Raptor, a subunit of mTORC1 for recruiting substrates for mTORC1. Although gene ontology enrichment analysis of these proteins suggested that SAA displays a promiscuous protein interaction, phosphoproteomics profiling revealed that the SAA modulated phosphoproteins were mainly enriched in the signaling pathways of PI3K-Akt-mTOR, which is closely related to cell growth and proliferation. This was confirmed by the biochemical assay with purified mTORC1, a Western blot assay with phospho-specific antibodies, and a cellular thermal shift assay. Our work discovered that SAA is a covalent ligand for protein modification and mTORC1 is one of its targets. Moreover, our work demonstrated that the integrative profiling of chemoproteomics and phosphoproteomics can be a powerful tool for target deconvolution for bioactive natural products.
研究领域:
药理学
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蛋白质组学
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癌症研究
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分子生物学
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生物化学
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PubMed
高影响因子
Journal of Inflammation Research
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2021
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IF 6.922
Qianxue Mou,Ke Yao,Meng Ye,Bowen Zhao,Yuanyuan Hu,Xiaotong Lou,Huixia Li,Hong Zhang,Yin Zhao
Purpose Optic nerve injury (ONI) causes neuroinflammation and neurodegeneration leading to visual deficits. The response of microglia has emerged as an impactful component of etiology in neurodegeneration. This study aimed to investigate the effect of SIRT1-mTORC1 signaling pathway in microglia regulation after ONI. Methods Cx3Cr1-Cre ERT2 / Raptor F/F and Cx3Cr1-Cre ERT2 / Sirt1 F/F mice were used to delete Raptor and Sirt1 in microglia, respectively. Optic nerve crush (ONC) model was established to mimic ONI. PLX5622, a highly specific inhibitor of the colony-stimulating factor 1 receptor (CSF1R), is used to eliminate microglia in optic nerve. Ionized calcium binding adaptor molecule 1 (Iba1) immunostaining was used to detect microglial activation. Retinal ganglion cells (RGCs) were quantified by Nissl staining and retinal whole-mount immunostaining with RNA-binding protein with multiple splicing (RBPMS). Axonal damage was valued by transmission electron microscopy (TEM). Results Microglial activation emerged on day 3 post ONC and was earlier than RGCs loss which occurred at day 5 after injury. Depleting microglia with PLX5622 could attenuate the loss of RGCs and axon damage after ONC. Gain- and loss-of-function studies revealed that SIRT1 determined the activation of microglia in optic nerve. In addition, microglia-specific deletion of Raptor resulted in decreased microglial activation. Interestingly, activating mTORC1 with CCT007093 could reverse the function of SIRT1 in regulating the process of microglial activation mediated RGCs loss. Conclusion Our study reveals a potential novel mechanism of SIRT1-mTORC1 pathway in microglia regulation, and indicates a therapeutic potential for the protection of RGCs in ONI.
研究领域:
神经科学
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眼科学
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分子生物学
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细胞生物学
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DOI
PubMed
高影响因子
Journal of Functional Foods
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2020
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IF 3.701
ShiFa Ruan,ShiJian Xiang,WenFeng Wu,SiWei Cao,QunQun Du,ZhuXian Wang,TingTing Chen,Qun Shen,Li Liu,HuoJi Chen,LiDong Weng,HongXia Zhu,Qiang Liu
We applied a label-free proteomic method to explore the mechanisms of Licorice flavonoid anti-acne effects in rat. Acne model was established in the back of rats as model group (MDL), then treated with licorice flavonoid (LCF), while none treated rats as control groups (CTR). In MDL, 314 differentially expressed proteins (DEPs) and 27 significantly differentially expressed proteins (SDEPs) were identified compared to what was identified in CTR. While in LCF, 359 DEPs and 15 SDEPs were identified in comparison to MDL. Bioinformatics analysis showed that pathways related to metabolism, tight junction, PI3K-Akt signaling, focal adhesion, regulation of actin cytoskeleton, and leukocyte transendothelial migration were activated. The results of proteomics data were validated by qRT-PCR and western blot. Transdermal administration of LCF may exert anti-acne effects by inhibiting PI3K-Akt signaling pathway and mitochondrial activity. Hence, our results elucidated the underlying mechanisms of LCF anti-acne effect.
研究领域:
药理学
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皮肤科
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蛋白质组学
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分子生物学
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DOI
高影响因子
IMMUNOBIOLOGY
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2023
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IF 2.8
Zepeng Chen,Qinglong Gu,Ruichao Chen
Ulcerative colitis (UC) is a chronic inflammatory disease affecting the colon that can be influenced by microRNAs (miRNAs). This study aims to investigate the impact of miR-146a-5p on lipopolysaccharide (LPS)-induced Caco-2/HT-29 cell autophagy and NLRP3 inflammasome activation and the underlying mechanism, with the aim of identifying potential therapeutic targets. We used LPS to establish Caco-2/HT-29 cell models and measured cell viability by CCK-8. The levels of miR-146a-5p, RNF8, markers of NLRP3 inflammasome activation and autophagy, proteins involved in the Notch1/mTORC1 pathway, and inflammatory factors were assessed by RT-qPCR, Western blot, and ELISA. Intestinal epithelial barrier function was evaluated by measuring transepithelial electrical resistance. Autophagic flux was measured using tandem fluorescent-labeled LC3. miR-146a-5p was highly-expressed in LPS-induced Caco-2/HT-29 cells, and autophagy flux was blocked at the autolysosomal stage after LPS induction. Inhibition of miR-146a-5p suppressed NLRP3 inflammasome activation, reduced intestinal epithelial barrier damage, and facilitated autophagy inhibition in LPS-induced Caco-2/HT-29 cells. The autophagy inhibitor NH4Cl partially nullified the inhibitory effects of miR-146a-5p inhibition on NLRP3 inflammation activation. miR-146a-5p targeted RNF8, and silencing RNF8 partly abrogated the action of miR-146a-5p inhibition on promoting autophagy and inhibiting NLRP3 inflammasome activation. miR-146a-5p inhibition suppressed the Notch1/mTORC1 pathway activation by upregulating RNF8. Inhibition of the Notch1/mTORC1 pathway partially nullified the function of silencing RNF8 on inhibiting autophagy and bolstering NLRP3 inflammasome activation. In conclusion, miR-146a-5p inhibition may be a potential therapeutic approach for UC, as it facilitates autophagy of LPS-stimulated Caco-2/HT-29 cells, inhibits NLRP3 inflammasome activation, and reduces intestinal epithelial barrier damage by upregulating RNF8 and suppressing the Notch1/mTORC1 pathway.
研究领域:
炎症性肠病
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分子生物学
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细胞生物学
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药理学
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DOI
PubMed
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
·
2020
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IF 6.551
Huan Wu,Yuexin Wei,Yu Zhou,Chunlan Long,Yifan Hong,Yan Fu,Tianxin Zhao,Junke Wang,Yuhao Wu,Shengde Wu,Lianju Shen,Guanghui Wei
Bisphenol S (BPS) is now used as an alternative of bisphenol A (BPA), but has been implicated in male reproductive dysfunction—including diminished sperm number and quality and altered hormonal concentrations. However, the mechanisms of action subserving these effects remains unclear. In the present study, BPS at doses of 50 mg/kg bw and 100 mg/kg bw caused defects in the integrity of the blood-testis barrier (BTB) and apical ectoplasmic specialization (ES), and we also delineated an underlying molecular mechanism of action. BPS induced F-actin and α-tubulin disorganization in seminiferous tubules, which in turn led to the truncation of actin filaments and microtubules. Additionally, BPS was found to perturb the expression of the actin-binding proteins Arp3 and Eps8, which are critical for the organization of the actin filaments. mTORC1 and mTORC2 manifest opposing roles in Sertoli cell junctional function, and we demonstrated that mTORC1/rpS6/Akt/MMP9 signaling was increased and that mTORC2/rictor activity was also attenuated. In summary, we showed that BPS-induced disruption of the BTB and apical ES perturbed normal spermatogenic function that was mediated by mTORC1 and mTORC2. The imbalance in mTORC1 and mTORC2, in turn, altered the expression of actin-binding proteins, resulting in the impairment of F-actin and MT organization, and inhibited the expression of junctional proteins at the BTB and apical ES.
研究领域:
毒理学
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生殖生物学
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细胞生物学
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PubMed
高影响因子
PLoS Pathogens
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2022
·Vol. 18
·期 9
·e1010808
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IF 7.464
Pan-Pan Hong,Cang Li,Guo-Juan Niu,Xiao-Fan Zhao,Jin-Xing Wang
Previous studies have shown that the mechanistic target of rapamycin complex 1 (mTORC1) signaling pathway has antiviral functions or is beneficial for viral replication, however, the detail mechanisms by which mTORC1 enhances viral infection remain unclear. Here, we found that proliferation of white spot syndrome virus (WSSV) was decreased after knockdown of mTor (mechanistic target of rapamycin) or injection inhibitor of mTORC1, rapamycin, in Marsupenaeus japonicus , which suggests that mTORC1 is utilized by WSSV for its replication in shrimp. Mechanistically, WSSV infects shrimp by binding to its receptor, polymeric immunoglobulin receptor (pIgR), and induces the interaction of its intracellular domain with Calmodulin. Calmodulin then promotes the activation of protein kinase B (AKT) by interaction with the pleckstrin homology (PH) domain of AKT. Activated AKT phosphorylates mTOR and results in the activation of the mTORC1 signaling pathway to promote its downstream effectors, ribosomal protein S6 kinase (S6Ks), for viral protein translation. Moreover, mTORC1 also phosphorylates eukaryotic translation initiation factor 4E-binding protein 1 (4EBP1), which will result in the separation of 4EBP1 from eukaryotic translation initiation factor 4E (eIF4E) for the translation of viral proteins in shrimp. Our data revealed a novel pathway for WSSV proliferation in shrimp and indicated that mTORC1 may represent a potential clinical target for WSSV control in shrimp aquaculture.
White spot syndrome virus (WSSV) is the causative pathogen of white spot disease (WSD) and represents the most destructive viral disease of shrimp. The virus has evolved various strategies to escape from host defenses or exploit host biological pathways for its reproduction. Studies on viral immune-escape mechanisms can provide new strategies for disease prevention and control in shrimp aquaculture. Mechanistic target of rapamycin (mTOR) plays a central role in the regulation of cell growth and metabolism, which nucleates two distinct protein complexes, mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2) with diverse functions at different levels of the signaling pathway. mTORC1 is reported to be exploited by viruses in their reproduction. However, the detail mechanism remains unclear. In this study, we identified a new mechanism of mTOR being hijacked by WSSV in shrimp ( Marsupenaeus japonicus ). WSSV infects shrimp by its receptor, pIgR and induces the interaction of the intracellular domain of pIgR with Calmodulin. Calmodulin subsequently promotes the activation of AKT by interaction with the pleckstrin homology domain of the kinase. Activated AKT phosphorylates mTOR and results in the activation of the mTORC1 signaling pathway to promote its downstream effectors, S6Ks, for viral protein synthesis. Moreover, mTORC1 also phosphorylates 4EBP1, which results in the separation of 4EBP1 from eIF4E for the translation of viral proteins in shrimp. Our study reveals a novel strategy for WSSV proliferation in shrimp and indicates that the components of mTORC1 may represent potential clinical targets for WSSV control in shrimp aquaculture.
研究领域:
水产养殖
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病毒学
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分子生物学
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免疫学
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PubMed
高影响因子
Autophagy
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2021
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IF 16.016
Kunpeng Liu,Dongbo Qiu,Xue Liang,Yingqi Huang,Yao Wang,Xin Jia,Kun Li,Jingyuan Zhao,Cong Du,Xiusheng Qiu,Jun Cui,Zhendong Xiao,Yunfei Qin,Qi Zhang
Lipid accumulation often leads to lipotoxic injuries to hepatocytes, which can cause nonalcoholic steatohepatitis. The association of inflammation with lipid accumulation in liver tissue has been studied for decades; however, key mechanisms have been identified only recently. In particular, it is still unknown how hepatic inflammation regulates lipid metabolism in hepatocytes. Herein, we found that PA treatment or direct stimulation of STING1 promoted, whereas STING1 deficiency impaired, MTORC1 activation, suggesting that STING1 is involved in PA-induced MTORC1 activation. Mechanistic studies revealed that STING1 interacted with several components of the MTORC1 complex and played an important role in the complex formation of MTORC1 under PA treatment. The involvement of STING1 in MTORC1 activation was dependent on SQSTM1, a key regulator of the MTORC1 pathway. In SQSTM1-deficient cells, the interaction of STING1 with the components of MTORC1 was weak. Furthermore, the impaired activity of MTORC1 via rapamycin treatment or STING1 deficiency decreased the numbers of LDs in cells. PA treatment inhibited lipophagy, which was not observed in STING1-deficient cells or rapamycin-treated cells. Restoration of MTORC1 activity via treatment with amino acids blocked lipophagy and LDs degradation. Finally, increased MTORC1 activation concomitant with STING1 activation was observed in liver tissues of nonalcoholic fatty liver disease patients, which provided clinical evidence for the involvement of STING1 in MTORC1 activation. In summary, we identified a novel regulatory loop of STING1-MTORC1 and explain how hepatic inflammation regulates lipid accumulation. Our findings may facilitate the development of new strategies for clinical treatment of hepatic steatosis.Abbreviations: AA: amino acid; ACTB: actin beta; cGAMP: cyclic GMP-AMP; CGAS: cyclic GMP-AMP synthase; DEPTOR: DEP domain containing MTOR interacting protein; EIF4EBP1: eukaryotic translation initiation factor 4E binding protein 1; FFAs: free fatty acids; GFP: green fluorescent protein; HFD: high-fat diet; HT-DNA: herring testis DNA; IL1B: interleukin 1 beta; LAMP1: lysosomal associated membrane protein 1; LDs: lipid droplets; MAP1LC3: microtubule associated protein 1 light chain 3; MAP1LC3B: microtubule associated protein 1 light chain 3 beta; MEFs: mouse embryonic fibroblasts; MLST8: MTOR associated protein, LST8 homolog; MT-ND1: mitochondrially encoded NADH: ubiquinone oxidoreductase core subunit 1; mtDNA: mitochondrial DNA; MTOR: mechanistic target of rapamycin kinase; MTORC1: MTOR complex 1; NAFL: nonalcoholic fatty liver; NAFLD: nonalcoholic fatty liver disease; NASH: nonalcoholic steatohepatitis; NPCs: non-parenchymal cells; PA: palmitic acid; PLIN2: perilipin 2; RD: regular diet; RELA: RELA proto-oncogene, NF-kB subunit; RPS6: ribosomal protein S6; RPS6KB1: ribosomal protein S6 kinase B1; RPTOR: regulatory associated protein of MTOR complex 1; RRAGA: Ras related GTP binding A; RRAGC: Ras related GTP binding C; SQSTM1: sequestosome 1; STING1: stimulator of interferon response cGAMP interactor 1; TBK1: TANK binding kinase 1; TGs: triglycerides; TREX1: three prime repair exonuclease 1.
研究领域:
分子生物学
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细胞生物学
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肝病学
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代谢
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炎症
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DOI
PubMed
高影响因子
Cell Reports
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2026
·Vol. 45
·期 2
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IF 6.9
Chenyi Xie,Xiaofang Cui,Wei Wei,Peicheng Hong,Lujia You,Ziyao Chen,Lin Li,Lan Wang,Na Wang,Ze-Guang Han
Metabolic dysregulation has been recognized as a crucial driver of tumorigenesis, particularly in metabolic dysfunction-associated steatotic liver disease (MASLD)-related hepatocellular carcinoma (HCC). However, the underlying mechanisms remain poorly understood. Here, we identify lysosome-localized insulin receptor tyrosine kinase substrate (IRTKS) as a key activator of the metabolic master regulator mTORC1 through phospho-antibody array screening. IRTKS forms membrane-associated condensates that selectively interact with the GTPase RRAGD, a key upstream regulator of mTORC1, thereby enhancing the sensitivity of mTORC1 to free amino acids. Notably, in hepatic knockin mice, Irtks-mediated mTORC1 hyperactivation promotes obesity, hepatic lipid accumulation, and the progression from MASLD to metabolic dysfunction-associated steatohepatitis and HCC. Conversely, pharmacological inhibition of mTORC1 or genetic ablation of Irtks ameliorates hepatic steatosis, inflammation, and metabolic dysfunction in mouse models. Our study establishes IRTKS as a central regulator of mTORC1-dependent metabolic reprogramming during hepatocarcinogenesis, providing potential therapeutic targets for MASLD-associated liver cancer.
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高影响因子
Journal of Agriculture and Food Research
·
2025
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IF 6.2
Ziyang Wang,Qinqin Ouyang,Xiaolin Liang,Hongxia Li,Haiying Guo,Rong Liu
Traditional Chinese medicine polysaccharides (TCMPs) have attracted growing attention due to their multi-target and multi-level therapeutic effects in the treatment of diabetes. In this study, we systematically evaluated the antidiabetic effect of three TCMPs, including Moringa oleifera Lam. polysaccharide (MOP), Morus alba L. polysaccharide (MLP) and Lycium barbarum polysaccharide (LBP) in T2DM mouse model. Among the three, MLP exhibited the most pronounced therapeutic efficacy, markedly alleviating hyperglycemia, insulin resistance, hepatic steatosis, and pathological lesions in the liver, pancreas. Liver metabolomic profiling revealed that MLP significantly modulated key glucose and lipid metabolic pathways, particularly bile acid and glycerolipid metabolism. Furthermore, we found MLP exerted its antidiabetic action through inhibition of the mTORC1 signaling pathway, leading to suppressed lipogenesis and enhanced fatty acid oxidation. Notably, MLP-mediated mTORC1 inhibition activated the PPARα–SIRT1 axis, thereby downregulating FOXO1-driven gluconeogenesis and promoting GLUT4-mediated glucose uptake. These findings suggest that MLP exerts comprehensive antidiabetic effects by targeting mTORC1-mediated metabolic reprogramming, offering promise as a natural therapeutic agent for T2DM.
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高影响因子
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