Notum protects against myocardial infarction-induced heart dysfunction by alleviating cardiac fibrosis

Background and Objective:Cardiac fibrosis is a pathological reparative process that follows myocardial infarctionand is associated with compromised cardiac systolic and reduced cardiac compliance.The Wnt signaling pathway is closely implicated in organ fibrosis,and Notum,a highly conserved secreted inhibitor,modulates Wnt signaling.The objective of this study was to explore the role and mechanism of Notum in cardiac fibrosis.Methods:A mouse model of cardiac remodeling was established through left coronary artery ligation surgery,with the addition of Notum injection following myocardial infarction surgery.The protective effect of Notum on myocardial infarction was assessed by evaluating cardiac function,including survival rate,echocardiographic assessment,and cardiac contraction analyses.Inflammatory cell necrosis and infiltration were confirmed through H&E and Masson staining.The expression of fibrosis-related genes andβ-catenin pathway markers was detected using Western blot quantificational RT-PCR(qRT-PCR).Additionally,EdU,wound healing,and immunofluorescence staining analyses were performed to detect the effect of Notum's in transforming growth factor beta-1(TGF-β1)induced myofibroblast transformation.Results:The administration of Notum treatment resulted in enhanced survival rates,improved cardiac function,and decreased necrosis and infiltration of inflammatory cells in mice subjected to left coronary artery ligation.Furthermore,Notum effectively impeded the senescence of cardiac fibroblasts and hindered their pathological transformation into cardiac fibroblasts.Additionally,it significantly reduced collagen production and attenuated the activation of the Wnt/β-catenin pathway.Our preliminary investigations successfully demonstrated the therapeutic potential of Notum in both fibroblasts in vitro and in a mouse model of myocardial infarction-induced cardiac fibrosis in vivo.Conclusion:Notum inhibition of the Wnt/β-catenin signaling pathway and cardiac fibroblast senescence ultimately hampers the onset of cardiac fibrosis.Our findings suggest that Notum could represent a new therapeutic strategy for the treatment of cardiac fibrosis.

Peroxisome proliferator-activated receptors gama ameliorates liver fibrosis in non-alcoholic fatty liver disease by inhibiting TGF-β/Smad signaling activation

Background:Nonalcoholic fatty liver disease(NAFLD)is a chronic condition characterized by a progressive decline in liver function,leading to disruptions in liver integrity and metabolic function,resulting in lipid deposition and excessive accumulation of extracellular matrix(ECM).The pathogenesis of NAFLD is complex and not yet fully understood,contributing to the absence of specific therapeutic strategies.Peroxisome proliferator-activated receptor gamma(PPARγ)is a ligand-activated transcription factor pivotal in regulating lipid and glucose metabolism.However,the impacts of PPARγon NAFLD remains insufficiently explored.Thus,this study aimed to investigate the role of PPARγin NAFLD and its underlying molecular mechanisms.Methods:Chemical detection kits were utilized to quantify collagen content,alanine aminotransferase(ALT),and aspartate aminotransferase(AST)level variations.Quantitative real-time polymerase chain reaction(qRT-PCR)was employed to assess alterations in extracellular matrix-related genes and inflammatory response genes in liver tissue and HepG2 cells,while western blotting was conducted to analyze the levels of both PPARγand the TGF-β/Smad signaling pathway.Results:Our findings unveiled significantly reduced PPARγexpression in a rat model of NAFLD,leading to subsequent activation of the TGF-β/Smad signaling pathway.Furthermore,PPARγactivation effectively mitigated NAFLD progression by inhibiting inflammation and fibrosis-related gene expression and collagen production.On a cellular level,PPARγactivation was found to inhibit the expression of extracellular matrix-related genes such as matrix metalloproteinase 2(MMP2)and matrix metalloproteinase 9(MMP9),along with inflammatory response genes interleukin(IL)-1βand IL-6.Additionally,PPARγactivation led to a significant decrease in the levels of ALT and AST.At the molecular level,PPARγnotably down-regulated the TGF-β/Smad signaling pathway,which is known to promote liver fibrosis.Conclusion:These groundbreaking findings underscore PPARγactivation as a promising therapeutic approach to delay NAFLD progression by targeting the TGF-β/Smad signaling pathway in hepatic cells.This highlights the potential of PPARγas a promising therapeutic target for NAFLD management in clinical settings.

Acute cold exposure triggers thermogenic memory in brown adipose tissue

1 Introduction Infants are born with a substantial amount of brown adipose tissue(BAT),primarily clustered around their upper back,shoulders,and upper chest[1].As age progresses,the primary BAT gradually diminishes,and concomitantly,de novo lipogenesis(DNL)continues to occur in subcutaneous adipose tissue throughout the body.The abundance of BAT in young children enhances their thermogenic capacity,making weight gain challenging and increasing resistance to cold temperatures.In adults.

FAM210A:Implications in mitochondrial dynamics and metabolic health

Brown adipose tissue(BAT),crucial for mammalian thermoregulation and energy metabolism,boasts a dense concentration of mitochondria.As a vital cellular organelle,mitochondria undergo substantial remodeling in cold environments,playing a pivotal role in maintaining body temperature and energy balance[1].Mitochondrial dynamics.

Unveiling metabolic flux changes during acute cold exposure

Controlling energy expenditure during acute cold exposure is a fundamental aspect of metabolic dynamics in organisms.However,prior studies on cold-induced thermogenesis faced limitations,primarily focusing on brown adipose tissue(BAT)and lacking precise in vivo flux measurements.This editorial aims to highlight the recent research by Bornstein et al.providing a comprehensive and quantitative insight into the intricate alterations in metabolic flux that drive this phenomenon[1].

I prostanoid receptor activation attenuates pressure overload-induced cardiac hypertrophy by enhancing glucose oxidation

Heart failure(HF)is one of the leading causes of mortality and morbidity worldwide.Despite current treatments can improve cardiac dysfunction in HF patients,the overall mortality rate remains high,indicating more effective therapeutic strategies for HF are needed.