Insulin plays a crucial role in the metabolic priming and proliferation of neural stem cells(NSCs).However,insulin resistance(IR)is associated with impaired NSC proliferation and cognitive dysfunction,which are the ha...Insulin plays a crucial role in the metabolic priming and proliferation of neural stem cells(NSCs).However,insulin resistance(IR)is associated with impaired NSC proliferation and cognitive dysfunction,which are the hallmarks of psychiatric disorders(PDs).In addition to insulin,de novo lipogenesis(DNL)also plays an essential role in NSC proliferation and function as it supplies fatty acids for membrane phospholipid synthesis and cell signaling.However,enhanced DNL is associated with lipid/fatty acid accumulation,IR,and impaired NSC proliferation.Intriguingly,data from lipidomic studies suggest that DNL could be enhanced before the onset of classical symptoms in patients with PDs.Further,evidence suggests that patients with PDs may develop IR during childhood or before adolescence;therefore,DNL could be enhanced preceding the development of IR.Regarding treatment,while most antidepressants and antipsychotic drugs have been shown to further deteriorate IR and stimulate DNL,various adjunctive drugs/therapies,including chemical,physical,and stem cell therapy,which have shown promising success in treating PDs,reduce DNL while enhancing insulin sensitivity,NSC proliferation,and cognitive function in laboratory animals.Preliminary clinical outcomes and future prospects of these adjunctive drugs/therapies,especially stem cell therapy in treating PDs including schizophrenia and depression,are discussed.展开更多
Hatchery-roared juvenile black sea breams are characterized by a low level of highly unsaturated fatty acids in their bodies, as compared with wild fish. To assess the effect of docosahaxaenoic acid （DHA） on lipegen...Hatchery-roared juvenile black sea breams are characterized by a low level of highly unsaturated fatty acids in their bodies, as compared with wild fish. To assess the effect of docosahaxaenoic acid （DHA） on lipegenic and lipelysis enzymes, one-year fish were roared on a casein-based purified diet and a DHA fortified diet （ 1.5% DHA ethyl ester/kg diet） for 60 d, followed with a period of 55 d for starvation. Dietary DHA was effectively incorporated into the fish body. Fortification of DHA depressed activities of glucose-6-phosphate dehydrogenase and NADP-isocitrate dehydrogenase as lipogenic enzymes in the hepatopancroas and intraperitoneal fat body. Carnitine palmitoyltransferase as lipolysis enzyme in the hepatopancreas was active in the DHA fortified fish. Starvation after feeding experiment induced increased carnitine palmitoyltransferase activity in both control and DHA fortified fish and the activity remained higher in the DHA fortified fish, while the monoenes were selectively consumed prior to highly unsaturated fatty acids. These results indicated that dietary DHA depressed lipogenesis and activated lipolysis.展开更多
This experiment studied hepatic lipogenesis associated with biochemical changes in overfed Landaise Geese and China Xupu geese. Twenty healthy male Landaise geese and 20 healthy male Xupu geese, hatched on the same da...This experiment studied hepatic lipogenesis associated with biochemical changes in overfed Landaise Geese and China Xupu geese. Twenty healthy male Landaise geese and 20 healthy male Xupu geese, hatched on the same day under the same feeding conditions, were selected as experimental animals. The animals were divided into two groups and each breed served as an experimental group. Per goose of per experimental group served for a repeat. Brown rice was selected as test diet. After overfeeding for 21 d and then slaughtering, the biochemical changes of hepatic lipogenesis in the genetic susceptibility to fatty liver were evaluated. These results showed that （1） the weight of fatty liver of the two breeds of geese were 801 and 375 g （P〈0.05）, respectively. There were no differences on the abdominal fat pat, filet total and filet pectoralis major in the two breeds experimental of the geese group （P〈0.05） and no difference on body and filet skin plus subcutaneous adipose tissue （P〉0.05） was found; （2） in these two breeds of geese, there were no differences on very-lowdensity lipoprotein （VLDL）, cholesteryl esters （CE） （P〈0.05）, free cholesterol （FC）, triglycerides （TG）, phospholipids （PL） and protein （P 〈 0.05）; （3） there were no differences on activities of malic enzyme （ME）, glucose-6-phosphatedehydrogenase （G6PDH）, acetyl-CoA-carboxylas （ACX）, fatty acid synthase （FAS）, and mRNA level of ME in the two experimental breeds of geese groups （P 〈0.05）; （4） test in Landaise geese group showed that there was no significant correlation with the specific enzymatic activities, while in Xupu geese group, the liver weight was negatively correlated to the specific activity of ACX and positively to that of ME; （5） in these overfed geese, ME activity appeared to be a major factor involved in the genetic susceptibility to hepatic steatosis and it determined the hepatic lipogenesis capacity.展开更多
Lipid metabolism and adipocyte differentiation are reglulated by networking of transcription factors. It is generally known that three factors, peroxisome proliferator-activated receptor y （PPARγ）, CCAAT/element-bi...Lipid metabolism and adipocyte differentiation are reglulated by networking of transcription factors. It is generally known that three factors, peroxisome proliferator-activated receptor y （PPARγ）, CCAAT/element-binding protein a （C/EBPa） and sterol regulatory element binding protein-1 （SREBP1）, play fundamental roles in metabolic pathways. And they are also important in adipocyte differentiation. Expressions of these factors are regulated by some compounds such as fatty acids or some steroid hormones （insulin） which is stimulated by the nutritional level. Furthermore, these factors are related to some metabolic diseases including type II diabetes and obesity, Lots of researches have focused on relationships between the factors and the genetic diseases. Different functions of factors on inducing the adipocyte differentiation are other hot spots according to previous studies. This paper summarized these studies and gave a limpid description of structures and functions of these genes.展开更多
Testosterone is closely associated with lipid metabolism and known to affect body fat composition and muscle mass in males.However,the mechanisms by which testosterone acts on lipid metabolism are not yet fully unders...Testosterone is closely associated with lipid metabolism and known to affect body fat composition and muscle mass in males.However,the mechanisms by which testosterone acts on lipid metabolism are not yet fully understood,especially in teleosts.In this study,cyp17a1-/-zebrafish(Danio rerio)exhibited excessive visceral adipose tissue(VAT),lipid content,and up-regulated expression and activity of hepatic de novo lipogenesis(DNL)enzymes.The assay for transposase accessible chromatinwithsequencing(ATAC-seq)results demonstrated that chromatin accessibility of DNL genes was increased in cyp17a1-/-fish compared to cyp17a1+/+male fish,including stearoyl-CoA desaturase(scd)and fatty acid synthase(fasn).Androgen response element(ARE)motifs in the androgen signaling pathway were significantly enriched in cyp17a1+/+male fish but not in cyp17a1-/-fish.Both androgen receptor(ar)-/-and wildtype(WT)zebrafish administered with Ar antagonist flutamide displayed excessive visceral adipose tissue,lipid content,and up-regulated expression and activity of hepatic de novo lipogenesis enzymes.The Ar agonist BMS-564929 reduced the content of VAT and lipid content,and down-regulated acetyl-CoA carboxylase a(acaca),fasn,and scd expression.Mechanistically,the rescue effect of testosterone on cyp17a1-/-fish in terms of phenotypes was abolished when ar was additionally depleted.Collectively,these findings reveal that testosterone inhibits lipid deposition by down-regulating DNL genes via Ar in zebrafish,thus expanding our understanding of the relationship between testosterone and lipid metabolism in teleosts.展开更多
The signal transduction network in regulating lipid metabolism is a hot topic of biomedical research. Recent research endeavors reveal that intracellular stress signaling from a cellular organelle called endoplasmic r...The signal transduction network in regulating lipid metabolism is a hot topic of biomedical research. Recent research endeavors reveal that intracellular stress signaling from a cellular organelle called endoplasmic reticulum (ER) is critically involved in lipid homeostasis and the development of metabolic disease. The ER is a site where newly-synthesized proteins are folded and assembled into their three-dimensional structures, modified and transported to their precise cellular destinations. A wide range of biochemical, physiological and pathological stimuli can interrupt the protein folding process in the ER and cause accumulation of unfolded or misfolded proteins in the ER lumen, a condition referred to as ER stress. To cope with this stress condition, the ER has evolved highly-specifi c signaling pathways collectively termed Unfolded Protein Response (UPR) or ER stress response. The UPR regulates transcriptionaland translational programs, affecting broad aspects of cellular metabolism and cell fate. Lipogenesis, the metabolic process of de novo lipid biosynthesis, occurs primarily in the liver where metabolic signals regulate expression of key enzymes in glycolytic and lipogenic pathways. Recent studies suggest that the UPR plays crucial roles in modulating lipogenesis under metabolic conditions. Here we address some of recent representative evidence regarding the role of the UPR in lipogenesis.展开更多
Although significant advances have been made in understanding the pathophysiology of psychiatric disorders(PDs),therapeutic advances have not been very convincing.While psychotropic medications can reduce classical sy...Although significant advances have been made in understanding the pathophysiology of psychiatric disorders(PDs),therapeutic advances have not been very convincing.While psychotropic medications can reduce classical symptoms in patients with PDs,their long-term use has been reported to induce or exaggerate various pre-existing metabolic abnormalities including diabetes,obesity and non-alcoholic fatty liver disease(NAFLD).The mechanism(s)underlying these metabolic abnormalities is not clear;however,lipid/fatty acid accumulation due to enhanced de novo lipogenesis(DNL)has been shown to reduce membrane fluidity,increase oxidative stress and inflammation leading to the development of the aforementioned metabolic abnormalities.Intriguingly,emerging evidence suggest that DNL dysregulation and fatty acid accumulation could be the major mechanisms associated with the development of obesity,diabetes and NAFLD after long-term treatment with psychotropic medications in patients with PDs.In support of this,several adjunctive drugs comprising of anti-oxidants and antiinflammatory agents,that are used in treating PDs in combination with psychotropic medications,have been shown to reduce insulin resistance and development of NAFLD.In conclusion,the above evidence suggests that DNL could be a potential pathological factor associated with various metabolic abnormalities,and a new avenue for translational research and therapeutic drug designing in PDs.展开更多
Aronia melamocarpa (AM) is a rich source of anthocyanins, which are known to help prevent obesity. The cyanidine-3-O-galactoside enriched AM extract (AM-Ex) containing more cyanidine-3-O-galactoside than conventional ...Aronia melamocarpa (AM) is a rich source of anthocyanins, which are known to help prevent obesity. The cyanidine-3-O-galactoside enriched AM extract (AM-Ex) containing more cyanidine-3-O-galactoside than conventional AM extract was recently developed. The objective of this study was to examine the effect of AM-Ex on adipogenesis and its action mechanisms in vitro using 3T3-L1 adipocytes. To examine the anti-obesity effect of AM-Ex, 3T3-L1 cells were induced adipocyte differentiation and incubated with various concentration of AM-Ex. Lipid accumulation, cellular triglyceride content, mRNA expression of transcription factors and adipogenic genes were analyzed. Treatment with 100 - 400 μg/mL of AM-Ex resulted in a dose-dependent decrease in adipocyte differentiation and triglyceride accumulation. mRNA expression of adipogenic transcription factors, such as peroxisome proliferator-activated receptor gamma, CCAAT/enhancer binding protein α, sterol regulatory element-binding protein 1 were decreased. The level of gene expression of adipogenesis and lipogenesis-related genes, such as adipocyte protein 2, lipoprotein lipase, acetyl-CoA carboxylase, ATP-citrate lyase and fatty acid synthase were decreased. These results suggest that AM-Ex alleviated risk factors related to obesity by modulating multiple pathways associated with adipogenesis.展开更多
This study investigates if the anti-tumor effect of Pterostilbene in the SKOV3 ovarian cancer(OC)cell line involves inhibition of cell metabolism and tested in this effect involves modulating AMPK and Akt-induced regu...This study investigates if the anti-tumor effect of Pterostilbene in the SKOV3 ovarian cancer(OC)cell line involves inhibition of cell metabolism and tested in this effect involves modulating AMPK and Akt-induced regulation of mTORC1.Initially,SKOV3 cells were cultured in the humidified conditions in DMEM media for 24 h with or without increasing concentration of Pterostilbene.Then,the cells were incubated with Pterostilbene(IC_(50)=50μM)under similar conditions with or without pre-incubation with Dorsomorphin,an AMPK inhibitor.In a dose-dependent manner,Pterostilbene inhibited SKOV3 cell survival and increased their lysate levels of lactate dehydrogenase(LDH)and single-stranded DNA(ssDNA).When SKOV3 cells were treated with 50μM Pterostilbene,Pterostilbene significantly suppressed cell migration and invasion,reduced lysate levels of lactic acid and the optical density of Oil Red O staining,and increased lysate glucose levels.It also increased levels of malondialdehyde(MDA),reactive oxygen species(ROS),and induced intrinsic cell apoptosis by upregulating protein levels of Bax and cleaved caspase-3 and reducing protein levels of Bcl-2.Besides,Pterostilbene reduced mRNA levels of sterol regulatory element-binding protein 1(SREBP-1),fatty acid synthase(FAS),acetyl CoA carboxylase-1(ACC-1),and AMP-activated protein kinase(AMPK).Furthermore,Pterostilbene increased the protein levels of p-AMPK,p-p53,p-raptor,p-TSC-2,but significantly decreased protein levels of p-Akt,p-TSC-2,p-mTOR,p-S6K1,and p-4E-BP.Treatment with Dorsomorphin(CC)abolished all the anti-tumorigenesis effects afforded by Pterostilbene and prevented Pterostilbene-induced phosphorylation of Akt,p53,and mTOR.In conclusion,the tumorsuppressive effect of Pterostilbene in SKOV3 cells involves the induction of ROS and inhibition of dysregulation cell metabolism mainly due to AMPK-induced Akt-dependent or independent suppression of mTOR.展开更多
Background: De novo lipogenesis (DNL) is a critical event for the development of tumors, in the present work,we revealed the role of propofol in colorectal cancer (CRC) cell proliferation. Methods: Western blotting (W...Background: De novo lipogenesis (DNL) is a critical event for the development of tumors, in the present work,we revealed the role of propofol in colorectal cancer (CRC) cell proliferation. Methods: Western blotting (WB), Real-timePCR, and luciferase combined with chromatin immunoprecipitation (ChIP) were used to identify the mechanismunderlying propofol-modulated cell proliferation in CRC cells. Results: Herein, we showed that propofol suppressedcell proliferation, which was attributed to the inhibition of DNL characterized by reduced fatty acid synthase (FASN),acetyl-coA carboxylase alpha (ACCA), and stearoyl-coA desaturase-1 (SCD1) expression. Mechanically, propofolstimulation decreased sterol regulatory element-binding proteins-1c (SREBP-1c) mature and nuclear translocation,which further decreased SCD1 transactivation confirmed by luciferase and ChIP analysis, while no significantdifference in total SREBP1c was observed. What’s more, supplementation of Monounsaturated fatty acid (MuFA)could reverse the inhibitory effect of propofol on cell proliferation. Conclusion: Taken together, these resultssuggested propofol modulated cell proliferation is dependent on SREBP1c-mediated DNL.展开更多
文摘Insulin plays a crucial role in the metabolic priming and proliferation of neural stem cells(NSCs).However,insulin resistance(IR)is associated with impaired NSC proliferation and cognitive dysfunction,which are the hallmarks of psychiatric disorders(PDs).In addition to insulin,de novo lipogenesis(DNL)also plays an essential role in NSC proliferation and function as it supplies fatty acids for membrane phospholipid synthesis and cell signaling.However,enhanced DNL is associated with lipid/fatty acid accumulation,IR,and impaired NSC proliferation.Intriguingly,data from lipidomic studies suggest that DNL could be enhanced before the onset of classical symptoms in patients with PDs.Further,evidence suggests that patients with PDs may develop IR during childhood or before adolescence;therefore,DNL could be enhanced preceding the development of IR.Regarding treatment,while most antidepressants and antipsychotic drugs have been shown to further deteriorate IR and stimulate DNL,various adjunctive drugs/therapies,including chemical,physical,and stem cell therapy,which have shown promising success in treating PDs,reduce DNL while enhancing insulin sensitivity,NSC proliferation,and cognitive function in laboratory animals.Preliminary clinical outcomes and future prospects of these adjunctive drugs/therapies,especially stem cell therapy in treating PDs including schizophrenia and depression,are discussed.
文摘Hatchery-roared juvenile black sea breams are characterized by a low level of highly unsaturated fatty acids in their bodies, as compared with wild fish. To assess the effect of docosahaxaenoic acid （DHA） on lipegenic and lipelysis enzymes, one-year fish were roared on a casein-based purified diet and a DHA fortified diet （ 1.5% DHA ethyl ester/kg diet） for 60 d, followed with a period of 55 d for starvation. Dietary DHA was effectively incorporated into the fish body. Fortification of DHA depressed activities of glucose-6-phosphate dehydrogenase and NADP-isocitrate dehydrogenase as lipogenic enzymes in the hepatopancroas and intraperitoneal fat body. Carnitine palmitoyltransferase as lipolysis enzyme in the hepatopancreas was active in the DHA fortified fish. Starvation after feeding experiment induced increased carnitine palmitoyltransferase activity in both control and DHA fortified fish and the activity remained higher in the DHA fortified fish, while the monoenes were selectively consumed prior to highly unsaturated fatty acids. These results indicated that dietary DHA depressed lipogenesis and activated lipolysis.
文摘This experiment studied hepatic lipogenesis associated with biochemical changes in overfed Landaise Geese and China Xupu geese. Twenty healthy male Landaise geese and 20 healthy male Xupu geese, hatched on the same day under the same feeding conditions, were selected as experimental animals. The animals were divided into two groups and each breed served as an experimental group. Per goose of per experimental group served for a repeat. Brown rice was selected as test diet. After overfeeding for 21 d and then slaughtering, the biochemical changes of hepatic lipogenesis in the genetic susceptibility to fatty liver were evaluated. These results showed that （1） the weight of fatty liver of the two breeds of geese were 801 and 375 g （P〈0.05）, respectively. There were no differences on the abdominal fat pat, filet total and filet pectoralis major in the two breeds experimental of the geese group （P〈0.05） and no difference on body and filet skin plus subcutaneous adipose tissue （P〉0.05） was found; （2） in these two breeds of geese, there were no differences on very-lowdensity lipoprotein （VLDL）, cholesteryl esters （CE） （P〈0.05）, free cholesterol （FC）, triglycerides （TG）, phospholipids （PL） and protein （P 〈 0.05）; （3） there were no differences on activities of malic enzyme （ME）, glucose-6-phosphatedehydrogenase （G6PDH）, acetyl-CoA-carboxylas （ACX）, fatty acid synthase （FAS）, and mRNA level of ME in the two experimental breeds of geese groups （P 〈0.05）; （4） test in Landaise geese group showed that there was no significant correlation with the specific enzymatic activities, while in Xupu geese group, the liver weight was negatively correlated to the specific activity of ACX and positively to that of ME; （5） in these overfed geese, ME activity appeared to be a major factor involved in the genetic susceptibility to hepatic steatosis and it determined the hepatic lipogenesis capacity.
基金Supported by National Natural Science Foundation Key Project of China(30430510)Natural Science Foundation Key Project of Heilongjiang Province(ZJN0604-01)National 973 Project of China(2006CB102105)
文摘Lipid metabolism and adipocyte differentiation are reglulated by networking of transcription factors. It is generally known that three factors, peroxisome proliferator-activated receptor y （PPARγ）, CCAAT/element-binding protein a （C/EBPa） and sterol regulatory element binding protein-1 （SREBP1）, play fundamental roles in metabolic pathways. And they are also important in adipocyte differentiation. Expressions of these factors are regulated by some compounds such as fatty acids or some steroid hormones （insulin） which is stimulated by the nutritional level. Furthermore, these factors are related to some metabolic diseases including type II diabetes and obesity, Lots of researches have focused on relationships between the factors and the genetic diseases. Different functions of factors on inducing the adipocyte differentiation are other hot spots according to previous studies. This paper summarized these studies and gave a limpid description of structures and functions of these genes.
基金supported by the National Key Research and Development Program,China (2022YFF1000300 to Z.Y.and2022YFD2401800 to G.Z.)Pilot Program A Project from the Chinese Academy of Sciences (XDA24010206 to Z.Y.)+3 种基金Foundation of Hubei Hongshan Laboratory (2021hskf013 to G.Z.and 2021hszd021 to Z.Y.)National Natural Science Foundation of China (31972779 to G.Z.)Youth Innovation Promotion Association of CAS (2020336 to G.Z.)State Key Laboratory of Freshwater Ecology and Biotechnology (2016FBZ05 to Z.Y.)。
文摘Testosterone is closely associated with lipid metabolism and known to affect body fat composition and muscle mass in males.However,the mechanisms by which testosterone acts on lipid metabolism are not yet fully understood,especially in teleosts.In this study,cyp17a1-/-zebrafish(Danio rerio)exhibited excessive visceral adipose tissue(VAT),lipid content,and up-regulated expression and activity of hepatic de novo lipogenesis(DNL)enzymes.The assay for transposase accessible chromatinwithsequencing(ATAC-seq)results demonstrated that chromatin accessibility of DNL genes was increased in cyp17a1-/-fish compared to cyp17a1+/+male fish,including stearoyl-CoA desaturase(scd)and fatty acid synthase(fasn).Androgen response element(ARE)motifs in the androgen signaling pathway were significantly enriched in cyp17a1+/+male fish but not in cyp17a1-/-fish.Both androgen receptor(ar)-/-and wildtype(WT)zebrafish administered with Ar antagonist flutamide displayed excessive visceral adipose tissue,lipid content,and up-regulated expression and activity of hepatic de novo lipogenesis enzymes.The Ar agonist BMS-564929 reduced the content of VAT and lipid content,and down-regulated acetyl-CoA carboxylase a(acaca),fasn,and scd expression.Mechanistically,the rescue effect of testosterone on cyp17a1-/-fish in terms of phenotypes was abolished when ar was additionally depleted.Collectively,these findings reveal that testosterone inhibits lipid deposition by down-regulating DNL genes via Ar in zebrafish,thus expanding our understanding of the relationship between testosterone and lipid metabolism in teleosts.
基金Supported partially by the American Heart Association (AHA) Scientist Development Award (0635423Z)the AHA Grant-in-Aid (09GRNT2280479)+1 种基金the Department of Defense Breast Cancer Research Program (BC095179P1)the Karmanos Cancer Institute Pilot Grant
文摘The signal transduction network in regulating lipid metabolism is a hot topic of biomedical research. Recent research endeavors reveal that intracellular stress signaling from a cellular organelle called endoplasmic reticulum (ER) is critically involved in lipid homeostasis and the development of metabolic disease. The ER is a site where newly-synthesized proteins are folded and assembled into their three-dimensional structures, modified and transported to their precise cellular destinations. A wide range of biochemical, physiological and pathological stimuli can interrupt the protein folding process in the ER and cause accumulation of unfolded or misfolded proteins in the ER lumen, a condition referred to as ER stress. To cope with this stress condition, the ER has evolved highly-specifi c signaling pathways collectively termed Unfolded Protein Response (UPR) or ER stress response. The UPR regulates transcriptionaland translational programs, affecting broad aspects of cellular metabolism and cell fate. Lipogenesis, the metabolic process of de novo lipid biosynthesis, occurs primarily in the liver where metabolic signals regulate expression of key enzymes in glycolytic and lipogenic pathways. Recent studies suggest that the UPR plays crucial roles in modulating lipogenesis under metabolic conditions. Here we address some of recent representative evidence regarding the role of the UPR in lipogenesis.
文摘Although significant advances have been made in understanding the pathophysiology of psychiatric disorders(PDs),therapeutic advances have not been very convincing.While psychotropic medications can reduce classical symptoms in patients with PDs,their long-term use has been reported to induce or exaggerate various pre-existing metabolic abnormalities including diabetes,obesity and non-alcoholic fatty liver disease(NAFLD).The mechanism(s)underlying these metabolic abnormalities is not clear;however,lipid/fatty acid accumulation due to enhanced de novo lipogenesis(DNL)has been shown to reduce membrane fluidity,increase oxidative stress and inflammation leading to the development of the aforementioned metabolic abnormalities.Intriguingly,emerging evidence suggest that DNL dysregulation and fatty acid accumulation could be the major mechanisms associated with the development of obesity,diabetes and NAFLD after long-term treatment with psychotropic medications in patients with PDs.In support of this,several adjunctive drugs comprising of anti-oxidants and antiinflammatory agents,that are used in treating PDs in combination with psychotropic medications,have been shown to reduce insulin resistance and development of NAFLD.In conclusion,the above evidence suggests that DNL could be a potential pathological factor associated with various metabolic abnormalities,and a new avenue for translational research and therapeutic drug designing in PDs.
文摘Aronia melamocarpa (AM) is a rich source of anthocyanins, which are known to help prevent obesity. The cyanidine-3-O-galactoside enriched AM extract (AM-Ex) containing more cyanidine-3-O-galactoside than conventional AM extract was recently developed. The objective of this study was to examine the effect of AM-Ex on adipogenesis and its action mechanisms in vitro using 3T3-L1 adipocytes. To examine the anti-obesity effect of AM-Ex, 3T3-L1 cells were induced adipocyte differentiation and incubated with various concentration of AM-Ex. Lipid accumulation, cellular triglyceride content, mRNA expression of transcription factors and adipogenic genes were analyzed. Treatment with 100 - 400 μg/mL of AM-Ex resulted in a dose-dependent decrease in adipocyte differentiation and triglyceride accumulation. mRNA expression of adipogenic transcription factors, such as peroxisome proliferator-activated receptor gamma, CCAAT/enhancer binding protein α, sterol regulatory element-binding protein 1 were decreased. The level of gene expression of adipogenesis and lipogenesis-related genes, such as adipocyte protein 2, lipoprotein lipase, acetyl-CoA carboxylase, ATP-citrate lyase and fatty acid synthase were decreased. These results suggest that AM-Ex alleviated risk factors related to obesity by modulating multiple pathways associated with adipogenesis.
基金supported by the Deputyship for Research&Innovation,Ministry of Education in Saudi Arabia for funding this research work through the project number PNU-DRI-RI-20-012.
文摘This study investigates if the anti-tumor effect of Pterostilbene in the SKOV3 ovarian cancer(OC)cell line involves inhibition of cell metabolism and tested in this effect involves modulating AMPK and Akt-induced regulation of mTORC1.Initially,SKOV3 cells were cultured in the humidified conditions in DMEM media for 24 h with or without increasing concentration of Pterostilbene.Then,the cells were incubated with Pterostilbene(IC_(50)=50μM)under similar conditions with or without pre-incubation with Dorsomorphin,an AMPK inhibitor.In a dose-dependent manner,Pterostilbene inhibited SKOV3 cell survival and increased their lysate levels of lactate dehydrogenase(LDH)and single-stranded DNA(ssDNA).When SKOV3 cells were treated with 50μM Pterostilbene,Pterostilbene significantly suppressed cell migration and invasion,reduced lysate levels of lactic acid and the optical density of Oil Red O staining,and increased lysate glucose levels.It also increased levels of malondialdehyde(MDA),reactive oxygen species(ROS),and induced intrinsic cell apoptosis by upregulating protein levels of Bax and cleaved caspase-3 and reducing protein levels of Bcl-2.Besides,Pterostilbene reduced mRNA levels of sterol regulatory element-binding protein 1(SREBP-1),fatty acid synthase(FAS),acetyl CoA carboxylase-1(ACC-1),and AMP-activated protein kinase(AMPK).Furthermore,Pterostilbene increased the protein levels of p-AMPK,p-p53,p-raptor,p-TSC-2,but significantly decreased protein levels of p-Akt,p-TSC-2,p-mTOR,p-S6K1,and p-4E-BP.Treatment with Dorsomorphin(CC)abolished all the anti-tumorigenesis effects afforded by Pterostilbene and prevented Pterostilbene-induced phosphorylation of Akt,p53,and mTOR.In conclusion,the tumorsuppressive effect of Pterostilbene in SKOV3 cells involves the induction of ROS and inhibition of dysregulation cell metabolism mainly due to AMPK-induced Akt-dependent or independent suppression of mTOR.
基金supported by Zhuhai Science and Technology Plan Project in the Field of Social Development(2320004000157)National Natural Science Foundation of China(82072215,82272219)+1 种基金Shenzhen Science and Technology Program(JCYJ20210324134602006)Natural Science Foundation of Guangdong Province(2214050001873).
文摘Background: De novo lipogenesis (DNL) is a critical event for the development of tumors, in the present work,we revealed the role of propofol in colorectal cancer (CRC) cell proliferation. Methods: Western blotting (WB), Real-timePCR, and luciferase combined with chromatin immunoprecipitation (ChIP) were used to identify the mechanismunderlying propofol-modulated cell proliferation in CRC cells. Results: Herein, we showed that propofol suppressedcell proliferation, which was attributed to the inhibition of DNL characterized by reduced fatty acid synthase (FASN),acetyl-coA carboxylase alpha (ACCA), and stearoyl-coA desaturase-1 (SCD1) expression. Mechanically, propofolstimulation decreased sterol regulatory element-binding proteins-1c (SREBP-1c) mature and nuclear translocation,which further decreased SCD1 transactivation confirmed by luciferase and ChIP analysis, while no significantdifference in total SREBP1c was observed. What’s more, supplementation of Monounsaturated fatty acid (MuFA)could reverse the inhibitory effect of propofol on cell proliferation. Conclusion: Taken together, these resultssuggested propofol modulated cell proliferation is dependent on SREBP1c-mediated DNL.
