Leptin is the protein product encoded by the obese (ob)gene. It is a circulating hormone produced primarily by the adipose tissue. ob/ob mice with mutations of the gene encoding leptin become morbidly obese, infertile...Leptin is the protein product encoded by the obese (ob)gene. It is a circulating hormone produced primarily by the adipose tissue. ob/ob mice with mutations of the gene encoding leptin become morbidly obese, infertile, hyperphagic, hypothermic,and diabetic. Since the cloning of leptin in 1994, our knowledge in body weight regulation and the role played by leptin has increased substantially. We now know that leptin signals through its receptor, OB-R, which is a member of the cytokine receptor superfamily. Leptin serves as an adiposity signal to inform the brain the adipose tissue mass in a negative feedback loop regulating food intake and energy expenditure. Leptin also plays important roles in angiogenesis, immune function, fertility and bone formation. Humans with mutations in the gene encoding leptin are also morbidly obese and respond to leptin treatment,demonstrating that enhancing or inhibiting leptin’s activities in vivo may have potential therapeutic benefits.展开更多
AIM:To determine the associations between leptin and ghrelin concentrations and sustained virological response(SVR)in chronic hepatitis C patients with ste-atosis.METHODS:We retrospectively assessed 56 patients infect...AIM:To determine the associations between leptin and ghrelin concentrations and sustained virological response(SVR)in chronic hepatitis C patients with ste-atosis.METHODS:We retrospectively assessed 56 patients infected with hepatitis C virus(HCV)genotype-1 and 40 with HCV genotype-3.Patients with decompensated cirrhosis,and those with other causes of chronic liver disease,were excluded.Serum HCV-RNA concentra-tions were measured before the initiation of treatment;at weeks 12(for genotype 1 patients),24 and 48 during treatment;and 24 wk after the end of treatment.Genotype was determined using INNO-LIPA HCV as-says,and serum leptin and ghrelin concentrations were measured using enzyme-linked immunosorbent assay.Biopsy specimens were scored according to the Ishak system and steatosis was graded as mild,moderate,or severe,according to the Brunt classif ication.RESULTS:Overall,SVR was positively related to the presence of genotype-3,to biopsy-determined lower histological stage of liver disease,and lower grade of steatosis.Patients ≥ 40 years old tended to be less responsive to therapy.In genotype-1 infected pa-tients,SVR was associated with a lower grade of liver steatosis,milder fibrosis,and an absence of insulin resistance.Genotype-1 infected patients who did not achieve SVR had significantly higher leptin concen-trations at baseline,with significant increases as the severity of steatosis worsened,whereas those who achieved SVR had higher ghrelin concentrations.In genotype-3 infected patients,SVR was associated only with fibrosis stage and lower homeostasis model as-sessment insulin resistance at baseline,but not with the degree of steatosis or leptin concentrations.Geno-type-3 infected patients who achieved SVR showed signif icant decreases in ghrelin concentration at end of treatment.Baseline ghrelin concentrations were elevat-ed in responders of both genotypes who had moderate and severe steatosis.CONCLUSION:Increased serum leptin before treat-ment may predict non-SVR,especially in HCV geno-type-1 infected patients,whereas increased ghrelin may predict SVR in genotype-1.展开更多
Objective To study the role of placental leptin in intrauterine cord leptin production and its relationship with neonatal anthropometry. Methods Forty women and their babies (40) were enrolled in this study. Placent...Objective To study the role of placental leptin in intrauterine cord leptin production and its relationship with neonatal anthropometry. Methods Forty women and their babies (40) were enrolled in this study. Placental tissues were assayed for leptin mRNA by reverse transcription/polymerase chain reaction (RT/PCR), and assayed for the obese gene protein leptin by Western-blot and immunohistochemistry. Blood was taken from the umbilical cord of the babies at delivery. Serum leptin was measured by radio-immunoassay. Neonatal anthropometric measurements were recorded within 48 hours after delivery. Linear regression analysis was used to explore the relationship between placental leptin, cord leptin and neonatal anthropometric measures. Results The obese gene was expressed in placental tissue at comparable or greater levels than that in adipose tissue. The placentas of the small for gestational age (SGA) neonates expressed leptin mRNA and protein at significantly lower levels than those of the appropriate for gestational age (AGA) neonates (P=0.0034 and 0.0076), while the placentas of the large for gestational age (LGA) neonates expressed leptin mRNA and protein at significantly higher levels than those of the AGA neonates (P=0.043 and 0.021). Linear regression analysis showed placental ob gene transcription and leptin translation correlated significantly with cord leptin (r=0.39 and 0.43), and neonatal Ponderal Index (r=0.66 and 0.69). Conclusion The placenta provides a source of leptin for the growing fetus, and this placental leptin might be a growth factor in intrauterine fetal development.展开更多
Combined radiation-wound injury(CRWI) is characterized by blood vessel damage and pro-inflammatory cytokine deficiency. Studies have identified that the direct application of leptin plays a significant role in angioge...Combined radiation-wound injury(CRWI) is characterized by blood vessel damage and pro-inflammatory cytokine deficiency. Studies have identified that the direct application of leptin plays a significant role in angiogenesis and inflammation. We established a sustained and stable leptin expression system to study the mechanism. A lentivirus method was employed to explore the angiogenic potential and peripheral inflammation of irradiated human umbilical vein endothelial cells(HUVECs). Leptin was transfected into human placenta-derived mesenchymal stem cells(HPMSCs) with lentiviral vectors. HUVECs were irradiated by X-ray at a single dose of 20 Gy. Transwell migration assay was performed to assess the migration of irradiated HUVECs. Based on the Transwell systems, co-culture systems of HPMSCs and irradiated HUVECs were established. Cell proliferation was measured by cell counting kit-8(CCK-8) assay. The secretion of pro-inflammatory cytokines(human granulocyte macrophage-colony stimulating factor(GM-CSF), interleukin(IL)-1α, IL-6, and IL-8) was detected by enzyme-linked immunosorbent assay(ELISA). The expression of pro-angiogenic factors(vascular endothelial growth factor(VEGF) and basic fibroblast growth factor(b FGF)) mRNA was detected by real-time quantitative polymerase chain reaction(RT-qPCR) assay. Relevant molecules of the nuclear factor-κB(NF-κB) and Janus kinase(JAK)/signal transducer and activator of transcription(STAT) signaling pathways were detected by western blot assay. Results showed that leptin-modified HPMSCs(HPMSCs/leptin) exhibited better cell proliferation, migration, and angiogenic potential(expressed more VEGF and bFGF). In both the single HPMSCs/leptin and the co-culture systems of HPMSCs/leptin and irradiated HUVECs, the increased secretion of pro-inflammatory cytokines(human GM-CSF, IL-1α, and IL-6) was associated with the interaction of the NF-κB and JAK/STAT signaling pathways. We conclude that HPMSCs/leptin could promote angiogenic potential and peripheral inflammation of HUVECs after X-ray radiation.展开更多
Since the discovery of leptin as an adipokine in 1994, much progress has been made in the research about leptin. Circulating leptin binds to leptin receptor, activates STAT3-dependent and STAT3-independent signaling p...Since the discovery of leptin as an adipokine in 1994, much progress has been made in the research about leptin. Circulating leptin binds to leptin receptor, activates STAT3-dependent and STAT3-independent signaling pathways, and plays an effective role in energy home- ostasis, neuroendocrine function and metabolism mainly through acting on the central nervous system, especially the hypothalamus. Leptin resistance is considered as a key risk factor for obesity. Various mechanisms have been formu- lated in order to explain leptin resistance, including impairment in leptin transport, attenuation in leptin sig- naling, ER stress, inflammation and deficiency in autop- hagy. Here, we review our current knowledge about leptin action, leptin signaling and leptin resistance, hoping to provide new ideas for the battle against obesity.展开更多
文摘Leptin is the protein product encoded by the obese (ob)gene. It is a circulating hormone produced primarily by the adipose tissue. ob/ob mice with mutations of the gene encoding leptin become morbidly obese, infertile, hyperphagic, hypothermic,and diabetic. Since the cloning of leptin in 1994, our knowledge in body weight regulation and the role played by leptin has increased substantially. We now know that leptin signals through its receptor, OB-R, which is a member of the cytokine receptor superfamily. Leptin serves as an adiposity signal to inform the brain the adipose tissue mass in a negative feedback loop regulating food intake and energy expenditure. Leptin also plays important roles in angiogenesis, immune function, fertility and bone formation. Humans with mutations in the gene encoding leptin are also morbidly obese and respond to leptin treatment,demonstrating that enhancing or inhibiting leptin’s activities in vivo may have potential therapeutic benefits.
文摘AIM:To determine the associations between leptin and ghrelin concentrations and sustained virological response(SVR)in chronic hepatitis C patients with ste-atosis.METHODS:We retrospectively assessed 56 patients infected with hepatitis C virus(HCV)genotype-1 and 40 with HCV genotype-3.Patients with decompensated cirrhosis,and those with other causes of chronic liver disease,were excluded.Serum HCV-RNA concentra-tions were measured before the initiation of treatment;at weeks 12(for genotype 1 patients),24 and 48 during treatment;and 24 wk after the end of treatment.Genotype was determined using INNO-LIPA HCV as-says,and serum leptin and ghrelin concentrations were measured using enzyme-linked immunosorbent assay.Biopsy specimens were scored according to the Ishak system and steatosis was graded as mild,moderate,or severe,according to the Brunt classif ication.RESULTS:Overall,SVR was positively related to the presence of genotype-3,to biopsy-determined lower histological stage of liver disease,and lower grade of steatosis.Patients ≥ 40 years old tended to be less responsive to therapy.In genotype-1 infected pa-tients,SVR was associated with a lower grade of liver steatosis,milder fibrosis,and an absence of insulin resistance.Genotype-1 infected patients who did not achieve SVR had significantly higher leptin concen-trations at baseline,with significant increases as the severity of steatosis worsened,whereas those who achieved SVR had higher ghrelin concentrations.In genotype-3 infected patients,SVR was associated only with fibrosis stage and lower homeostasis model as-sessment insulin resistance at baseline,but not with the degree of steatosis or leptin concentrations.Geno-type-3 infected patients who achieved SVR showed signif icant decreases in ghrelin concentration at end of treatment.Baseline ghrelin concentrations were elevat-ed in responders of both genotypes who had moderate and severe steatosis.CONCLUSION:Increased serum leptin before treat-ment may predict non-SVR,especially in HCV geno-type-1 infected patients,whereas increased ghrelin may predict SVR in genotype-1.
文摘Objective To study the role of placental leptin in intrauterine cord leptin production and its relationship with neonatal anthropometry. Methods Forty women and their babies (40) were enrolled in this study. Placental tissues were assayed for leptin mRNA by reverse transcription/polymerase chain reaction (RT/PCR), and assayed for the obese gene protein leptin by Western-blot and immunohistochemistry. Blood was taken from the umbilical cord of the babies at delivery. Serum leptin was measured by radio-immunoassay. Neonatal anthropometric measurements were recorded within 48 hours after delivery. Linear regression analysis was used to explore the relationship between placental leptin, cord leptin and neonatal anthropometric measures. Results The obese gene was expressed in placental tissue at comparable or greater levels than that in adipose tissue. The placentas of the small for gestational age (SGA) neonates expressed leptin mRNA and protein at significantly lower levels than those of the appropriate for gestational age (AGA) neonates (P=0.0034 and 0.0076), while the placentas of the large for gestational age (LGA) neonates expressed leptin mRNA and protein at significantly higher levels than those of the AGA neonates (P=0.043 and 0.021). Linear regression analysis showed placental ob gene transcription and leptin translation correlated significantly with cord leptin (r=0.39 and 0.43), and neonatal Ponderal Index (r=0.66 and 0.69). Conclusion The placenta provides a source of leptin for the growing fetus, and this placental leptin might be a growth factor in intrauterine fetal development.
基金Project supported by the Special Fund for Cooperation of Local Government and College(Schools and Institutes)in Changchun,Jilin Province(No.17DY024),China。
文摘Combined radiation-wound injury(CRWI) is characterized by blood vessel damage and pro-inflammatory cytokine deficiency. Studies have identified that the direct application of leptin plays a significant role in angiogenesis and inflammation. We established a sustained and stable leptin expression system to study the mechanism. A lentivirus method was employed to explore the angiogenic potential and peripheral inflammation of irradiated human umbilical vein endothelial cells(HUVECs). Leptin was transfected into human placenta-derived mesenchymal stem cells(HPMSCs) with lentiviral vectors. HUVECs were irradiated by X-ray at a single dose of 20 Gy. Transwell migration assay was performed to assess the migration of irradiated HUVECs. Based on the Transwell systems, co-culture systems of HPMSCs and irradiated HUVECs were established. Cell proliferation was measured by cell counting kit-8(CCK-8) assay. The secretion of pro-inflammatory cytokines(human granulocyte macrophage-colony stimulating factor(GM-CSF), interleukin(IL)-1α, IL-6, and IL-8) was detected by enzyme-linked immunosorbent assay(ELISA). The expression of pro-angiogenic factors(vascular endothelial growth factor(VEGF) and basic fibroblast growth factor(b FGF)) mRNA was detected by real-time quantitative polymerase chain reaction(RT-qPCR) assay. Relevant molecules of the nuclear factor-κB(NF-κB) and Janus kinase(JAK)/signal transducer and activator of transcription(STAT) signaling pathways were detected by western blot assay. Results showed that leptin-modified HPMSCs(HPMSCs/leptin) exhibited better cell proliferation, migration, and angiogenic potential(expressed more VEGF and bFGF). In both the single HPMSCs/leptin and the co-culture systems of HPMSCs/leptin and irradiated HUVECs, the increased secretion of pro-inflammatory cytokines(human GM-CSF, IL-1α, and IL-6) was associated with the interaction of the NF-κB and JAK/STAT signaling pathways. We conclude that HPMSCs/leptin could promote angiogenic potential and peripheral inflammation of HUVECs after X-ray radiation.
基金Acknowledgments This work was supported by the National Basic Research Program of China （2013CB530601, 2011CB910201）, the National Natural Science Foundation of China （31571401, 81270954, 31030048, 81390350）, the Shanghai Rising Star Program （13QH1400800）. The Department of Biochemistry and Molecular Biology at Fudan University Shanghai Medical College is supported by the Shanghai Leading Academic Discipline Projects B 110 and by ＂985＂ Project 985III-YFX0302.
文摘Since the discovery of leptin as an adipokine in 1994, much progress has been made in the research about leptin. Circulating leptin binds to leptin receptor, activates STAT3-dependent and STAT3-independent signaling pathways, and plays an effective role in energy home- ostasis, neuroendocrine function and metabolism mainly through acting on the central nervous system, especially the hypothalamus. Leptin resistance is considered as a key risk factor for obesity. Various mechanisms have been formu- lated in order to explain leptin resistance, including impairment in leptin transport, attenuation in leptin sig- naling, ER stress, inflammation and deficiency in autop- hagy. Here, we review our current knowledge about leptin action, leptin signaling and leptin resistance, hoping to provide new ideas for the battle against obesity.
