Cancer cells undergo metabolic reprogramming to support cell proliferation,growth,and dissemination.Alterations in lipid metabolism,and specifically the uptake and synthesis of fatty acids(FAs),comprise onewelldocumen...Cancer cells undergo metabolic reprogramming to support cell proliferation,growth,and dissemination.Alterations in lipid metabolism,and specifically the uptake and synthesis of fatty acids(FAs),comprise onewelldocumented aspect of this reprogramming.Recent studies have revealed an expanded range of roles played by FA in promoting the aggressiveness of cancer while simultaneously identifying new potential targets for cancer therapy.This article provides a brief review of these advances in our understanding of FA metabolism in cancer,highlighting both recent discoveries and the inherent challenges caused by the metabolic plasticity of cancer cells in targeting lipid metabolism for cancer therapy.展开更多
Neural plasticity in the adult central nervous system involves the adaptation of myelination, including the formation of novel myelin sheaths by adult-born oligodendrocytes. Yet, mature oligodendrocytes slowly but con...Neural plasticity in the adult central nervous system involves the adaptation of myelination, including the formation of novel myelin sheaths by adult-born oligodendrocytes. Yet, mature oligodendrocytes slowly but constantly turn over their pre-existing myelin sheaths, thereby establishing an equilibrium of replenishment and degradation that may also be subject to adaptation with consequences for nerve conduction velocity. In this short review we highlight selected approaches to the normal turnover of adult myelin in vivo, from injecting radioactive precursors of myelin constituents in the 1960s to current strategies involving isotope labeling and tamoxifen-induced gene targeting.展开更多
Recent epidemiological studies indicate a strong linkbetween intrauterine under-nutrition and propensityof such off spring for developing obesity and meta-bolic syndrome in later life. Garg et al investigated the mec... Recent epidemiological studies indicate a strong linkbetween intrauterine under-nutrition and propensityof such off spring for developing obesity and meta-bolic syndrome in later life. Garg et al investigated the mechanistic basis of this phenomenon and its potential reversibility in rats. The authors found that rats experiencing gestational under-nutrition but fed normally after birth (IUGR) gained body mass with excessive subcutaneous and visceral fat. The IUGR rats were alsome tabolically inflexible since they showed similar rates of energy expenditure and O2consumption in the fedand fasted states. However, if such pups were food-restricted during lactation (PNGR), their metabolic profiles resembled those of control and IPGR (subject tofood restriction during pre- and postnatal periods) rats.Thus, postnatal caloric restriction superimposed on intrauterine under nutrition significantly improved insulinsensitivity and adiposity of rats that would otherwise develop metabolic inflexibility and visceral obesity. The observations of Garg et al , have serious implications interm of the design of the future experimental studiesas well as their clinical translation in humans.展开更多
BACKGROUND Perinatal exposure to a poor nutritional environment predisposes the progeny to the development of metabolic disease at the adult age,both in experimental models and humans.Numerous adaptive responses to ma...BACKGROUND Perinatal exposure to a poor nutritional environment predisposes the progeny to the development of metabolic disease at the adult age,both in experimental models and humans.Numerous adaptive responses to maternal protein restriction have been reported in metabolic tissues.However,the expression of glucose/fatty acid metabolism-related genes in adipose tissue and liver needs to be described.AIM To evaluate the metabolic impact of perinatal malnutrition,we determined malnutrition-associated gene expression alterations in liver and adipose tissue.METHODS In the present study,we evaluated the alterations in gene expression of glycolytic/Krebs cycle genes(Pyruvate dehydrogenase kinase 4 and citrate synthase),adipogenic and lipolytic genes and leptin in the adipose tissue of offspring rats at 30 d and 90 d of age exposed to maternal isocaloric low protein(LP)diet throughout gestation and lactation.We also evaluated,in the livers of the same animals,the same set of genes as well as the gene expression of the transcription factors peroxisome proliferator-activated receptor gamma coactivator 1,forkhead box protein O1 and hepatocyte nuclear factor 4 and of gluconeogenic genes.RESULTS In the adipose tissue,we observed a transitory(i.e.,at 30 d)downregulation of pyruvate dehydrogenase kinase 4,citrate synthase and carnitine palmitoyl transferase 1b gene expression.Such transcriptional changes did not persist in adult LP rats(90 d),but we observed a tendency towards a decreased gene expression of leptin(P=0.052).The liver featured some gene expression alterations comparable to the adipose tissue,such as pyruvate dehydrogenase kinase 4 downregulation at 30 d and displayed other tissue-specific changes,including citrate synthase and fatty acid synthase upregulation,but pyruvate kinase downregulation at 30 d in the LP group and carnitine palmitoyl transferase 1b downregulation at 90 d.These gene alterations,together with previously described changes in gene expression in skeletal muscle,may account for the metabolic a展开更多
基金This work was supported by the Startup funds at Duke University School of Medicine to M.C.and the National Institutes of Health(Grants No.5R01CA205001-03 and 5R01CA200853-03)to J.H.
文摘Cancer cells undergo metabolic reprogramming to support cell proliferation,growth,and dissemination.Alterations in lipid metabolism,and specifically the uptake and synthesis of fatty acids(FAs),comprise onewelldocumented aspect of this reprogramming.Recent studies have revealed an expanded range of roles played by FA in promoting the aggressiveness of cancer while simultaneously identifying new potential targets for cancer therapy.This article provides a brief review of these advances in our understanding of FA metabolism in cancer,highlighting both recent discoveries and the inherent challenges caused by the metabolic plasticity of cancer cells in targeting lipid metabolism for cancer therapy.
基金supported by the Deutsche Forschungsgemeinschaft(DFG,WE2720/2-2 and WE2720/4-1,both to HBW)
文摘Neural plasticity in the adult central nervous system involves the adaptation of myelination, including the formation of novel myelin sheaths by adult-born oligodendrocytes. Yet, mature oligodendrocytes slowly but constantly turn over their pre-existing myelin sheaths, thereby establishing an equilibrium of replenishment and degradation that may also be subject to adaptation with consequences for nerve conduction velocity. In this short review we highlight selected approaches to the normal turnover of adult myelin in vivo, from injecting radioactive precursors of myelin constituents in the 1960s to current strategies involving isotope labeling and tamoxifen-induced gene targeting.
文摘 Recent epidemiological studies indicate a strong linkbetween intrauterine under-nutrition and propensityof such off spring for developing obesity and meta-bolic syndrome in later life. Garg et al investigated the mechanistic basis of this phenomenon and its potential reversibility in rats. The authors found that rats experiencing gestational under-nutrition but fed normally after birth (IUGR) gained body mass with excessive subcutaneous and visceral fat. The IUGR rats were alsome tabolically inflexible since they showed similar rates of energy expenditure and O2consumption in the fedand fasted states. However, if such pups were food-restricted during lactation (PNGR), their metabolic profiles resembled those of control and IPGR (subject tofood restriction during pre- and postnatal periods) rats.Thus, postnatal caloric restriction superimposed on intrauterine under nutrition significantly improved insulinsensitivity and adiposity of rats that would otherwise develop metabolic inflexibility and visceral obesity. The observations of Garg et al , have serious implications interm of the design of the future experimental studiesas well as their clinical translation in humans.
基金Supported by the CAPES/COFECUB,No.797-14the National Council for Research–Brazil,No.477915/2012-4.
文摘BACKGROUND Perinatal exposure to a poor nutritional environment predisposes the progeny to the development of metabolic disease at the adult age,both in experimental models and humans.Numerous adaptive responses to maternal protein restriction have been reported in metabolic tissues.However,the expression of glucose/fatty acid metabolism-related genes in adipose tissue and liver needs to be described.AIM To evaluate the metabolic impact of perinatal malnutrition,we determined malnutrition-associated gene expression alterations in liver and adipose tissue.METHODS In the present study,we evaluated the alterations in gene expression of glycolytic/Krebs cycle genes(Pyruvate dehydrogenase kinase 4 and citrate synthase),adipogenic and lipolytic genes and leptin in the adipose tissue of offspring rats at 30 d and 90 d of age exposed to maternal isocaloric low protein(LP)diet throughout gestation and lactation.We also evaluated,in the livers of the same animals,the same set of genes as well as the gene expression of the transcription factors peroxisome proliferator-activated receptor gamma coactivator 1,forkhead box protein O1 and hepatocyte nuclear factor 4 and of gluconeogenic genes.RESULTS In the adipose tissue,we observed a transitory(i.e.,at 30 d)downregulation of pyruvate dehydrogenase kinase 4,citrate synthase and carnitine palmitoyl transferase 1b gene expression.Such transcriptional changes did not persist in adult LP rats(90 d),but we observed a tendency towards a decreased gene expression of leptin(P=0.052).The liver featured some gene expression alterations comparable to the adipose tissue,such as pyruvate dehydrogenase kinase 4 downregulation at 30 d and displayed other tissue-specific changes,including citrate synthase and fatty acid synthase upregulation,but pyruvate kinase downregulation at 30 d in the LP group and carnitine palmitoyl transferase 1b downregulation at 90 d.These gene alterations,together with previously described changes in gene expression in skeletal muscle,may account for the metabolic a
