Objective:Psoriasis is associated with lipid metabolism disorders,but the underlying mechanisms remain unclear.This study aims to investigate the role of trimethylamine Noxide(TMAO)in lipid metabolism dysregulation in...Objective:Psoriasis is associated with lipid metabolism disorders,but the underlying mechanisms remain unclear.This study aims to investigate the role of trimethylamine Noxide(TMAO)in lipid metabolism dysregulation in psoriasis.Methods:An imiquimod(IMQ)-induced psoriasis-like mouse model was used to assess lipid metabolism parameters,TMAO levels,and liver flavin monooxygenase 3(FMO3)mRNA expression.Blood samples from healthy individuals and psoriatic patients were collected to measure serum TMAO levels and lipid profiles.To clarify the role of TMAO in the lipid metabolism disorder of mice with psoriasis model,exogenous TMAO,choline,or 3,3-dimethyl-1-butanol(DMB)were administered via intraperitoneal injections or diet in IMQ-treated mice.Liver tissues from the mouse models were subjected to RNA sequencing to identify TMAO-regulated signaling pathways.Results:IMQ-induced psoriatic mice exhibited abnormal glucose,insulin,and lipid levels.IMQ treatment also downregulated the hepatic mRNA expression of glucose transporter 2(Glut2)and silence information regulator 1(Sirt1),while upregulating glucose transporter 4(Glut4)and peroxisome proliferator-activated receptor gamma(PPARγ).Elevated serum TMAO levels were observed in both psoriatic patients and IMQ-treated mice.Additionally,liver FMO3 mRNA expression was increased in the psoriatic mouse model.In patients,TMAO levels positively correlated with Psoriasis Area and Severity Index(PASI)scores,serum triglyceride(TG),and total cholesterol(TC)levels.The intraperitoneal injection of TMAO exacerbated lipid dysregulation in IMQ-treated mice.A choline-rich diet further aggravated lipid abnormalities and liver injury in psoriatic mice,whereas DMB treatment alleviated these effects.RNA-Seq analysis demonstrated that TMAO upregulated hepatic microRNA-122(miR-122),which may suppress the expression of gremlin 2(GREM2),thus contributing to lipid metabolism disorder.Conclusion:TMAO may promote lipid metabolism dysregulation in psoriasis by modulating the hepatic miR-122/GREM2 pathway.展开更多
To investigate the effects of allicin on chickens＇ lipid and antioxidant performance, Hy-laying hens＇ diets were replenished with 0 mg · kg-1, 50 mg · kg-1, 100 mg · kg-1, and 150 mg · kg-1 allic...To investigate the effects of allicin on chickens＇ lipid and antioxidant performance, Hy-laying hens＇ diets were replenished with 0 mg · kg-1, 50 mg · kg-1, 100 mg · kg-1, and 150 mg · kg-1 allicin for 42 days, respectively. The alanine aminotransferase（ALT）, aspartate aminotransferase（AST）, triglyceride（TG）, total cholesterol（TCHO）, high density lipoprotein（HDL）, and low density lipoprotein（LDL） levels were measured in chicken serum. Superoxide dismutase（SOD）, glutathione peroxidase（GSH-Px） activity and malondialdehyde（MDA） levels were measured in chicken serum and liver tissue homogenate. The results showed that the supplement dose of allicin tested did not significantly change the activity of ALT or AST（P〉0.05）; TG and CHOL levels decreased with the increase of allicin additive doses, and the difference between treatment groups and CG was significant（P〈0.05）, and there was the best effect with 100 mg · kg-1; allicin significantly reduced the content of MDA, and increased SOD and GSH-Px activities compared with CG（P〈0.05）, and 100 mg · kg-1 of allicin resulted in the strongest SOD and GSH-Px activity. The antioxidant function test results of liver tissue homogenate were consistant with that of serum. Our findings indicated that allicin could enhance antioxidant capacity and reduce blood lipid level in chickens and 100 mg · kg-1 was the optimal amount of allicin additives.展开更多
The nuclear receptor peroxisome proliferator-activated receptor γ（PPAR-γ） is a key transcriptional regulator of adipocyte differentiation.It also modulates the synthesis of adipocytokines in the adipose tissue.Its...The nuclear receptor peroxisome proliferator-activated receptor γ（PPAR-γ） is a key transcriptional regulator of adipocyte differentiation.It also modulates the synthesis of adipocytokines in the adipose tissue.Its polymorphisms are associated with the risk of type Ⅱ diabetes,obesity,cardiovascular diseases and cancer.In the present study,to investigate the regulatory mechanism of PPAR-γ gene on lipid metabolism,the computational prediction of peroxisome proliferator response elements（PPREs） was pursued with a genome-wide scale by using MEME/MAST method based on the information of TRANSFAC database,then GO and KEGG analyses were carried out.The results showed that a huge number of predicted target genes of PPAR-γ were significantly enriched in 36 GO terms（P〈0.05） and 10 KEGG pathways（P〈0.05） which were related closely to the lipid metabolism.The results should be a valuable resource for elucidation of the regulatory mechanism of PPAR-γ influence on lipid metabolism,also of the major importance to the diagnosis,prevention and treatment of the complex diseases such as obesity and diabete.展开更多
OBJECTIVE To investigate the protective effect and potential mechanism of desmethylbellidifolin(DMB)in chronic alcoholic fatty liver disease.METHODS C57BL/6 mice were randomly divided into five groups.Control,metadoxi...OBJECTIVE To investigate the protective effect and potential mechanism of desmethylbellidifolin(DMB)in chronic alcoholic fatty liver disease.METHODS C57BL/6 mice were randomly divided into five groups.Control,metadoxine and DMB group(high dose and low dose)mice were fed with Lieber-DeCarli liquid diet containing 5%alcohol for six weeks.Pair-fed group mice were fed with a liquid diet containing the same calories.After treatment,serum GOT,GPT,TG and hepatic T-CHO,TG,GSH,GSH-Px,SOD and CAT levels were measured.Ectopic liver lipid deposition was determined by oil red O and hematoxylin-eosin(HE)staining.Lipid metabolism and autophagy related genes expression were determined by real-time PCR and Western blotting.Electron microscope and laser scanning confocal microscope were used to detect autophagosome and autophagy flux.RESULTS DMB treatment markedly reduced serum TG,GOT and GPT levels in alcohol-induced mice,as well as hepatic levels of T-CHO,TG and MDA,while increased the GSH,GSH-Px,SOD and CAT levels in the liver.Oil red O and HE staining showed that the alcohol-induced lipid accumulation and hepatocyte morphology changes were significantly improved by DMB treatment.Mechanistically,the expression of stearoyl-CoA desaturase 1 and fatty acid synthase were significantly decreased,while lipolysis related hormone-sensitive lipase was elevated in mouse liver by DMB treatment.In addition,DMB could inhibit the phosphorylation of Akt and mTORC1,and activate autophagy process by inducing autophagy related genes expression,such as LC3,ATG5 and ATG7.Moreover,treatment with DMB notably increased the number of autolysosome and promote the autophagy flux,which may therefore induce the lipolysis and oxidation of lipids and prevent the alcohol-induced excessive lipid accumulation in the liver.CONCLUSION DMB exerts a protective role in alcoholic fatty liver disease by regulating the Akt-mTORC1 pathway mediated autophagy activation.展开更多
基金supported by the National Natural Science Foundation(82173426)the Natural Science Foundation of Hunan Province(2023JJ30984),China。
文摘Objective:Psoriasis is associated with lipid metabolism disorders,but the underlying mechanisms remain unclear.This study aims to investigate the role of trimethylamine Noxide(TMAO)in lipid metabolism dysregulation in psoriasis.Methods:An imiquimod(IMQ)-induced psoriasis-like mouse model was used to assess lipid metabolism parameters,TMAO levels,and liver flavin monooxygenase 3(FMO3)mRNA expression.Blood samples from healthy individuals and psoriatic patients were collected to measure serum TMAO levels and lipid profiles.To clarify the role of TMAO in the lipid metabolism disorder of mice with psoriasis model,exogenous TMAO,choline,or 3,3-dimethyl-1-butanol(DMB)were administered via intraperitoneal injections or diet in IMQ-treated mice.Liver tissues from the mouse models were subjected to RNA sequencing to identify TMAO-regulated signaling pathways.Results:IMQ-induced psoriatic mice exhibited abnormal glucose,insulin,and lipid levels.IMQ treatment also downregulated the hepatic mRNA expression of glucose transporter 2(Glut2)and silence information regulator 1(Sirt1),while upregulating glucose transporter 4(Glut4)and peroxisome proliferator-activated receptor gamma(PPARγ).Elevated serum TMAO levels were observed in both psoriatic patients and IMQ-treated mice.Additionally,liver FMO3 mRNA expression was increased in the psoriatic mouse model.In patients,TMAO levels positively correlated with Psoriasis Area and Severity Index(PASI)scores,serum triglyceride(TG),and total cholesterol(TC)levels.The intraperitoneal injection of TMAO exacerbated lipid dysregulation in IMQ-treated mice.A choline-rich diet further aggravated lipid abnormalities and liver injury in psoriatic mice,whereas DMB treatment alleviated these effects.RNA-Seq analysis demonstrated that TMAO upregulated hepatic microRNA-122(miR-122),which may suppress the expression of gremlin 2(GREM2),thus contributing to lipid metabolism disorder.Conclusion:TMAO may promote lipid metabolism dysregulation in psoriasis by modulating the hepatic miR-122/GREM2 pathway.
文摘To investigate the effects of allicin on chickens＇ lipid and antioxidant performance, Hy-laying hens＇ diets were replenished with 0 mg · kg-1, 50 mg · kg-1, 100 mg · kg-1, and 150 mg · kg-1 allicin for 42 days, respectively. The alanine aminotransferase（ALT）, aspartate aminotransferase（AST）, triglyceride（TG）, total cholesterol（TCHO）, high density lipoprotein（HDL）, and low density lipoprotein（LDL） levels were measured in chicken serum. Superoxide dismutase（SOD）, glutathione peroxidase（GSH-Px） activity and malondialdehyde（MDA） levels were measured in chicken serum and liver tissue homogenate. The results showed that the supplement dose of allicin tested did not significantly change the activity of ALT or AST（P〉0.05）; TG and CHOL levels decreased with the increase of allicin additive doses, and the difference between treatment groups and CG was significant（P〈0.05）, and there was the best effect with 100 mg · kg-1; allicin significantly reduced the content of MDA, and increased SOD and GSH-Px activities compared with CG（P〈0.05）, and 100 mg · kg-1 of allicin resulted in the strongest SOD and GSH-Px activity. The antioxidant function test results of liver tissue homogenate were consistant with that of serum. Our findings indicated that allicin could enhance antioxidant capacity and reduce blood lipid level in chickens and 100 mg · kg-1 was the optimal amount of allicin additives.
基金Supported by National 973 Project of China (2006CB102105)Natural Science Foundation Key Project of Heilongjiang Province (ZJN0604-01)National 863 Project of China (2006AA10A120)
文摘The nuclear receptor peroxisome proliferator-activated receptor γ（PPAR-γ） is a key transcriptional regulator of adipocyte differentiation.It also modulates the synthesis of adipocytokines in the adipose tissue.Its polymorphisms are associated with the risk of type Ⅱ diabetes,obesity,cardiovascular diseases and cancer.In the present study,to investigate the regulatory mechanism of PPAR-γ gene on lipid metabolism,the computational prediction of peroxisome proliferator response elements（PPREs） was pursued with a genome-wide scale by using MEME/MAST method based on the information of TRANSFAC database,then GO and KEGG analyses were carried out.The results showed that a huge number of predicted target genes of PPAR-γ were significantly enriched in 36 GO terms（P〈0.05） and 10 KEGG pathways（P〈0.05） which were related closely to the lipid metabolism.The results should be a valuable resource for elucidation of the regulatory mechanism of PPAR-γ influence on lipid metabolism,also of the major importance to the diagnosis,prevention and treatment of the complex diseases such as obesity and diabete.
文摘OBJECTIVE To investigate the protective effect and potential mechanism of desmethylbellidifolin(DMB)in chronic alcoholic fatty liver disease.METHODS C57BL/6 mice were randomly divided into five groups.Control,metadoxine and DMB group(high dose and low dose)mice were fed with Lieber-DeCarli liquid diet containing 5%alcohol for six weeks.Pair-fed group mice were fed with a liquid diet containing the same calories.After treatment,serum GOT,GPT,TG and hepatic T-CHO,TG,GSH,GSH-Px,SOD and CAT levels were measured.Ectopic liver lipid deposition was determined by oil red O and hematoxylin-eosin(HE)staining.Lipid metabolism and autophagy related genes expression were determined by real-time PCR and Western blotting.Electron microscope and laser scanning confocal microscope were used to detect autophagosome and autophagy flux.RESULTS DMB treatment markedly reduced serum TG,GOT and GPT levels in alcohol-induced mice,as well as hepatic levels of T-CHO,TG and MDA,while increased the GSH,GSH-Px,SOD and CAT levels in the liver.Oil red O and HE staining showed that the alcohol-induced lipid accumulation and hepatocyte morphology changes were significantly improved by DMB treatment.Mechanistically,the expression of stearoyl-CoA desaturase 1 and fatty acid synthase were significantly decreased,while lipolysis related hormone-sensitive lipase was elevated in mouse liver by DMB treatment.In addition,DMB could inhibit the phosphorylation of Akt and mTORC1,and activate autophagy process by inducing autophagy related genes expression,such as LC3,ATG5 and ATG7.Moreover,treatment with DMB notably increased the number of autolysosome and promote the autophagy flux,which may therefore induce the lipolysis and oxidation of lipids and prevent the alcohol-induced excessive lipid accumulation in the liver.CONCLUSION DMB exerts a protective role in alcoholic fatty liver disease by regulating the Akt-mTORC1 pathway mediated autophagy activation.
