Peroxisome proliferator-activated receptor gamma(PPARγor PPARG)is a ligand-activated transcription factor belonging to the nuclear hormone receptor superfamily.It plays a master role in the differentiation and prolif...Peroxisome proliferator-activated receptor gamma(PPARγor PPARG)is a ligand-activated transcription factor belonging to the nuclear hormone receptor superfamily.It plays a master role in the differentiation and proliferation of adipose tissues.It has two major isoforms,PPARγ1 and PPARγ2,encoded from a single gene using two separate promoters and alternative splicing.Among them,PPARγ2 is most abundantly expressed in adipocytes and plays major adipogenic and lipogenic roles in the tissue.Furthermore,it has been shown that PPARγ2 is also expressed in the liver,specifically in hepatocytes,and its expression level positively correlates with fat accumulation induced by pathological conditions such as obesity and diabetes.Knockout of the hepatic Pparg gene ameliorates hepatic steatosis induced by diet or genetic manipulations.Transcriptional activation of Pparg in the liver induces the adipogenic program to store fatty acids in lipid droplets as observed in adipocytes.Understanding how the hepatic Pparg gene expression is regulated will help develop preventative and therapeutic treatments for non-alcoholic fatty liver disease(NAFLD).Due to the potential adverse effect of hepatic Pparg gene deletion on peripheral tissue functions,therapeutic interventions that target PPAR g for fatty liver diseases require fine-tuning of this gene's expression and transcriptional activity。展开更多
Objective:To investigate the effect of Shenqi Compound Formula (SCF) on peroxisome proliferators-activated receptor γ (PPARγ) in white adipose tissue of rats with macrovascular lesion in early stage of diabetes. Met...Objective:To investigate the effect of Shenqi Compound Formula (SCF) on peroxisome proliferators-activated receptor γ (PPARγ) in white adipose tissue of rats with macrovascular lesion in early stage of diabetes. Methods: Corresponding treatment was given to rats in model group, Ramipril group, normal control group, low dosage SCF group and high dosage SCF group respectively for 32 days. The expressions of PPARγ and adiponectin Messenger RNA (mRNA) were detected by real-time reverse transcriptase poly-merase chain reaction. Results: The expressions of PPARγ and adiponectin mRNA increased significantly in both low and high dosage SCF groups as compared with the model group, and a positive linear correlation was found between the expressions of PPARγ and adiponectin mRNA. Conclusions: SCF can prevent macrovascular lesion in early stage of diabetes, which is possibly related with up-regulating expressions of PPARγ and activating PPARγ.展开更多
Objective To investigate effects of clenbuterol （CLB） on the peroxisome proliferators- activated receptor γ （PPARγ） expression in adipose tissues of rats. Methods Twenty adult female Sprague-Dawley rats were ran...Objective To investigate effects of clenbuterol （CLB） on the peroxisome proliferators- activated receptor γ （PPARγ） expression in adipose tissues of rats. Methods Twenty adult female Sprague-Dawley rats were randomly divided into 4 groups （5 rats per group）. CLB solved in normal saline solution was given at the dose of 0 mg/kg body weight （bw） （group A, as the control）, 0.4 mg/kg bw （group B, low-dose group）, 2.0 mg/kg bw （group C, mid-dose group）, and 18.5 mg/kg bw （group D, high-dose group）for 14 d by gavage consecutively, respectively. Methods of immunohistochemistry, quantitative Real-time PCR and Western blotting were performed to detect expression of PPARγ in the adipose tissue samples. Results PPARγ-positive immunostaining was strong in the controls and weak in the experimental groups. There was no difference on PPARγmRNA and protein between the low-dose group and the control （P〉0.05）. With the increase of CLB doses, expression levels of PPARγmRNA and protein were significantly lower in mid- or high-dose group than those in the control （19〈0.01）. Conclusions The PPARγ expression in adipose tissues of rats could be down-regulated after CLB exposure, and the decrease became more severe with the increasing doses.展开更多
Uncontrolled microglial activation is decisively involved in the neuroinflammatory pathogenesis of brain diseases. Consequently, suppression of microglial overactivation appears to be a strategy for the prevention of ...Uncontrolled microglial activation is decisively involved in the neuroinflammatory pathogenesis of brain diseases. Consequently, suppression of microglial overactivation appears to be a strategy for the prevention of nerve injury. In this paper, a novel vanadium complex, vanadyl N-(p-N,Ndimethylaminophenylcarbamoylmethyl)iminodiacetate(VO(p-dmada)), was synthesized from vanadyl sulfate and N,N-dimethyl-p-phenylenediamine, which was structurally characterized by Fourier transform infrared spectrum and ESI-MS analysis. The effect of VO(p-dmada) on neuroinflammation was investigated by using the models of lipopolysaccharide(LPS)-induced BV2 microglial cells and BALB/c mice.Our data demonstrated that VO(p-dmada) significantly suppressed microglial activation by downregulating inflammatory mediators and associated proteins, and inactivating nuclear factor-κ B(NF-κ B) signaling pathway. VO(p-dmada) also upregulated peroxisome proliferator activated receptor gamma(PPARγ) by reducing transglutaminase 2 and heat shock protein 60 expression. Co-treatment with PPARγ antagonist GW9662 significantly impeded the inhibitory effect of VO(p-dmada) on LPS-induced neuroinflammation.These cumulative findings demonstrated that VO(p-dmada) is a potential new drug for the treatment of neuroinflammation-related neurodegenerative diseases.展开更多
Background:Non-alcoholic liver disease is of increased concern and contributing to economic burdens not only in developing countries but in developed countries as well.Identifying the biomarker of early diagnosis and ...Background:Non-alcoholic liver disease is of increased concern and contributing to economic burdens not only in developing countries but in developed countries as well.Identifying the biomarker of early diagnosis and early intervention approaches for non-alcoholic liver disease is unmet and required further investigation.Although the alpha-ketoglutarate(a-KG)is recently proposed to be a potential biomarker in differentiating patients with obesity from those with non-alcoholic liver disease,how a-ketoglutatate is involved in the fatty liver progression is not clear.Methods:A high-fat diet(HFD)feeding animal model,liver functional assays,and molecular approaches were adopted to clarify the impact of a-KG in fatty liver progression.Results:In the current study,it was found that dietary a-KG would inhibit weight gain in male and female mice fed with a normal chew or HFD.HFD feeding caused fatty liver in male mice,but a-KG treatment could substantially inhibit hepatic steatosis progression.Biochemical studies revealed the possible linkage of a-KG protective functions to lipid metabolism.Further analysis identified the important role of peroxisome proliferator-activated receptors in beneficial a-KG-mediated effects on fatty liver progression.Conclusions:The current study demonstrates the therapeutic potential of a-KG and how it may be used,via dietary supplementation,as a preventive intervention for non-alcoholic liver disease in obese patients.展开更多
基金This work was supported by USA National Institutes of Health(NIH)grant,R01DK093774 to Y.K.Lee.
文摘Peroxisome proliferator-activated receptor gamma(PPARγor PPARG)is a ligand-activated transcription factor belonging to the nuclear hormone receptor superfamily.It plays a master role in the differentiation and proliferation of adipose tissues.It has two major isoforms,PPARγ1 and PPARγ2,encoded from a single gene using two separate promoters and alternative splicing.Among them,PPARγ2 is most abundantly expressed in adipocytes and plays major adipogenic and lipogenic roles in the tissue.Furthermore,it has been shown that PPARγ2 is also expressed in the liver,specifically in hepatocytes,and its expression level positively correlates with fat accumulation induced by pathological conditions such as obesity and diabetes.Knockout of the hepatic Pparg gene ameliorates hepatic steatosis induced by diet or genetic manipulations.Transcriptional activation of Pparg in the liver induces the adipogenic program to store fatty acids in lipid droplets as observed in adipocytes.Understanding how the hepatic Pparg gene expression is regulated will help develop preventative and therapeutic treatments for non-alcoholic fatty liver disease(NAFLD).Due to the potential adverse effect of hepatic Pparg gene deletion on peripheral tissue functions,therapeutic interventions that target PPAR g for fatty liver diseases require fine-tuning of this gene's expression and transcriptional activity。
文摘Objective:To investigate the effect of Shenqi Compound Formula (SCF) on peroxisome proliferators-activated receptor γ (PPARγ) in white adipose tissue of rats with macrovascular lesion in early stage of diabetes. Methods: Corresponding treatment was given to rats in model group, Ramipril group, normal control group, low dosage SCF group and high dosage SCF group respectively for 32 days. The expressions of PPARγ and adiponectin Messenger RNA (mRNA) were detected by real-time reverse transcriptase poly-merase chain reaction. Results: The expressions of PPARγ and adiponectin mRNA increased significantly in both low and high dosage SCF groups as compared with the model group, and a positive linear correlation was found between the expressions of PPARγ and adiponectin mRNA. Conclusions: SCF can prevent macrovascular lesion in early stage of diabetes, which is possibly related with up-regulating expressions of PPARγ and activating PPARγ.
基金supported by Science and Technology Planning Project of Guangzhou City,China(No.201300000114)
文摘Objective To investigate effects of clenbuterol （CLB） on the peroxisome proliferators- activated receptor γ （PPARγ） expression in adipose tissues of rats. Methods Twenty adult female Sprague-Dawley rats were randomly divided into 4 groups （5 rats per group）. CLB solved in normal saline solution was given at the dose of 0 mg/kg body weight （bw） （group A, as the control）, 0.4 mg/kg bw （group B, low-dose group）, 2.0 mg/kg bw （group C, mid-dose group）, and 18.5 mg/kg bw （group D, high-dose group）for 14 d by gavage consecutively, respectively. Methods of immunohistochemistry, quantitative Real-time PCR and Western blotting were performed to detect expression of PPARγ in the adipose tissue samples. Results PPARγ-positive immunostaining was strong in the controls and weak in the experimental groups. There was no difference on PPARγmRNA and protein between the low-dose group and the control （P〉0.05）. With the increase of CLB doses, expression levels of PPARγmRNA and protein were significantly lower in mid- or high-dose group than those in the control （19〈0.01）. Conclusions The PPARγ expression in adipose tissues of rats could be down-regulated after CLB exposure, and the decrease became more severe with the increasing doses.
基金financially supported by grants from the National Natural Science Foundation of China(No.21877081)the China Postdoctoral Science Foundation(No.2021M692210)+2 种基金Guangdong Provincial Key S&T Program(No.2018B030336001)the Shenzhen Science and Technology Innovation Commission(No.JCYJ20200109110001818)the Shenzhen-Hong Kong Institute of brain Science-Shenzhen Fundamental Research institutions(No.2022SHIBS0003)。
文摘Uncontrolled microglial activation is decisively involved in the neuroinflammatory pathogenesis of brain diseases. Consequently, suppression of microglial overactivation appears to be a strategy for the prevention of nerve injury. In this paper, a novel vanadium complex, vanadyl N-(p-N,Ndimethylaminophenylcarbamoylmethyl)iminodiacetate(VO(p-dmada)), was synthesized from vanadyl sulfate and N,N-dimethyl-p-phenylenediamine, which was structurally characterized by Fourier transform infrared spectrum and ESI-MS analysis. The effect of VO(p-dmada) on neuroinflammation was investigated by using the models of lipopolysaccharide(LPS)-induced BV2 microglial cells and BALB/c mice.Our data demonstrated that VO(p-dmada) significantly suppressed microglial activation by downregulating inflammatory mediators and associated proteins, and inactivating nuclear factor-κ B(NF-κ B) signaling pathway. VO(p-dmada) also upregulated peroxisome proliferator activated receptor gamma(PPARγ) by reducing transglutaminase 2 and heat shock protein 60 expression. Co-treatment with PPARγ antagonist GW9662 significantly impeded the inhibitory effect of VO(p-dmada) on LPS-induced neuroinflammation.These cumulative findings demonstrated that VO(p-dmada) is a potential new drug for the treatment of neuroinflammation-related neurodegenerative diseases.
基金Funding for this work was provided by 2017 AASLDF Pinnacle Research Development Award and Rhode Island Foundation#134279.
文摘Background:Non-alcoholic liver disease is of increased concern and contributing to economic burdens not only in developing countries but in developed countries as well.Identifying the biomarker of early diagnosis and early intervention approaches for non-alcoholic liver disease is unmet and required further investigation.Although the alpha-ketoglutarate(a-KG)is recently proposed to be a potential biomarker in differentiating patients with obesity from those with non-alcoholic liver disease,how a-ketoglutatate is involved in the fatty liver progression is not clear.Methods:A high-fat diet(HFD)feeding animal model,liver functional assays,and molecular approaches were adopted to clarify the impact of a-KG in fatty liver progression.Results:In the current study,it was found that dietary a-KG would inhibit weight gain in male and female mice fed with a normal chew or HFD.HFD feeding caused fatty liver in male mice,but a-KG treatment could substantially inhibit hepatic steatosis progression.Biochemical studies revealed the possible linkage of a-KG protective functions to lipid metabolism.Further analysis identified the important role of peroxisome proliferator-activated receptors in beneficial a-KG-mediated effects on fatty liver progression.Conclusions:The current study demonstrates the therapeutic potential of a-KG and how it may be used,via dietary supplementation,as a preventive intervention for non-alcoholic liver disease in obese patients.
