Thyroid hormone excess secondary to global type 3 deiodinase(DIO3)deficiency leads to increased locomotor activity and reduced adiposity,but also to concurrent alterations in parameters of the leptin-melanocortin syst...Thyroid hormone excess secondary to global type 3 deiodinase(DIO3)deficiency leads to increased locomotor activity and reduced adiposity,but also to concurrent alterations in parameters of the leptin-melanocortin system that would predict obesity.To distinguish the underlying contributions to the energy balance phenotype of Dlo3 deficiency,we generated mice with thyroid hormone excess targeted to pro-opiomelanocortin(POMC)-expressing cells via cell-specific DIO3 inactivation.These mice exhibit a male-specific phenotype of reduced hypothalamic Pomc expression,hyperphagia,and increased activity in brown adipose tissue,with adiposity and serum levels of leptin and thyroid hormones remained normal.These male mice also manifest a marked and widespread hypothalamic reduction in the expression of bone morphogenetic receptor 1a(BMPR1A),which has been shown to cause similar phenotypes when inactivated in PoMC-expressing cells.Our results indicate that developmental overexposure to thyroid hormone in PoMC-expressing cells programs energy balance mechanisms in a sexually dimorphic manner by suppressing adult hypothalamic BMPR1A expression.展开更多
目的 :观察青年和老年期大鼠下丘脑弓状核阿黑皮素原 m RNA(POMC m RNA)的表达水平。 方法 :应用原位杂交技术显示 POMC m RNA和用计算机图像分析观察杂交信号的强弱及阳性细胞的面积。 结果 :与青年组相比 ,老年组下丘脑弓状核及其附...目的 :观察青年和老年期大鼠下丘脑弓状核阿黑皮素原 m RNA(POMC m RNA)的表达水平。 方法 :应用原位杂交技术显示 POMC m RNA和用计算机图像分析观察杂交信号的强弱及阳性细胞的面积。 结果 :与青年组相比 ,老年组下丘脑弓状核及其附近区域 POMC m RNA阳性神经元的平均灰度值下降 ;POMC m RNA阳性神经元的数目无明显变化。结论 :老年期 POMC m RNA阳性神经元相应的 m RNA表达水平下降可能是下丘脑 POMC基因衍生肽表达水平下降的原因之一。展开更多
Fragmented data suggest that bisphenol AF(BPAF),a chemical widely used in a variety of products,might have potential impacts on the hypothalamus.Here,we employed male neonatal mice following maternal exposure to explo...Fragmented data suggest that bisphenol AF(BPAF),a chemical widely used in a variety of products,might have potential impacts on the hypothalamus.Here,we employed male neonatal mice following maternal exposure to explore the effects of low-dose BPAF on hypothalamic development by RNA-sequencing.We found that maternal exposure to approximately 50μg/(kg·day)BPAF from postanal day(PND)0 to PND 15 altered the hypothalamic transcriptome,primarily involving the pathways and genes associated with extracellular matrix(ECM)and intercellular adhesion,neuroendocrine regulation,and neurological processes.Further RNA analysis confirmed the changes in the expression levels of concerned genes.Importantly,we further revealed that low-dose BPAF posed a stimulatory impact on pro-opiomelanocortin(POMC)neurons in the arcuate nucleus of the hypothalamus and induced the browning of inguinal white adipose tissue.All findings indicate that developmental exposure to low-dose BPAF could interfere with hypothalamic development and thereby lead to alterations in the metabolism.Interestingly,5000μg/(kg·day)BPAF caused slighter,non-significant or even inverse alterations than the low dose of 50μg/(kg·day),displaying a dose-independent effect.Further observations suggest that the the dose-independent effects of BPAF might be associated with oxidative stress and inflammatory responses caused by the high dose.Overall,our study highlights a risk of low-dose BPAF to human neuroendocrine regulation and metabolism.展开更多
OBJECTIVE:To observe the influence of different moxibustion durations on hypothalamic pro-opiomelanocortin(POMC)and prodynorphin(PDYN)mRNA expressions and plasmaβ-endorphin(β-EP)content in rheumatoid arthritis(RA)ra...OBJECTIVE:To observe the influence of different moxibustion durations on hypothalamic pro-opiomelanocortin(POMC)and prodynorphin(PDYN)mRNA expressions and plasmaβ-endorphin(β-EP)content in rheumatoid arthritis(RA)rats,to understand the mechanism of moxibustion analgesia and its dose-effect relationship.METHODS:Twelve male Wistar rats were randomly selected from 48 male Wistar rats as a normal control group.The RA model was created by raising rats in a windy(blowing with electric fan),cold(6℃±2℃),and wet(80%-90%humidity)environment for 20 days,12 h each day.This was followed byinjectionofFreund'scompleteadjuvant(0.15 mL)into the ankle.Then,rats were randomly divided into a model group,moxibustion groupⅠ,and moxibustion groupⅡ,with 12 rats in each group.In moxibustion groupsⅠandⅡ,moxibustion was given at Shenshu(BL 23)and Zusanli(ST 36)for 20and 40 min,respectively,once daily for 15 days.Hypothalamic POMC and PDYN mRNA expression levels and plasmaβ-EP content were determined.RESULTS:Compared with the normal group,the pressure pain threshold decreased,while the hypothalamic POMC and PDYN mRNA expression levels and plasmaβ-EP content increased in the moxibustion groups(P<0.01).Compared with the model group,the pressure pain threshold,hypothalamic POMC and PDYN mRNA expression levels and plasmaβ-EP content in the moxibustion groups increased significantly(P<0.01).Compared the moxibustion groupⅠ,the pain threshold,hypothalamic POMC and PDYN mRNA expression levels and plasmaβ-EP content in moxibustion groupⅡsignificantly increased(P<0.01).CONCLUSION:Moxibustion has an analgesic effect and increases hypothalamic POMC and PDYN mRNA expression levels and plasmaβ-EP content inRArats.TheanalgesiceffectinmoxibustiongroupⅡisbetterthanthatinmoxibustiongroupⅠ.展开更多
基金We are grateful for the technical support of the Molecular Phenotyping,Histopathology and Histomorphometry,Confocal Microscopy,and Physiology Core facilities at MaineHealth Institute for Research.These core facilities are supported by grants P30GM106391,U54GM115516,and P20GM121301 from the National Institute of General Medical SciencesThis work was supported by grant DK095908(to A.H.)from the National Institute of Diabetes,Digestive and Kidney Diseases,National Institutes of Health,USA.
文摘Thyroid hormone excess secondary to global type 3 deiodinase(DIO3)deficiency leads to increased locomotor activity and reduced adiposity,but also to concurrent alterations in parameters of the leptin-melanocortin system that would predict obesity.To distinguish the underlying contributions to the energy balance phenotype of Dlo3 deficiency,we generated mice with thyroid hormone excess targeted to pro-opiomelanocortin(POMC)-expressing cells via cell-specific DIO3 inactivation.These mice exhibit a male-specific phenotype of reduced hypothalamic Pomc expression,hyperphagia,and increased activity in brown adipose tissue,with adiposity and serum levels of leptin and thyroid hormones remained normal.These male mice also manifest a marked and widespread hypothalamic reduction in the expression of bone morphogenetic receptor 1a(BMPR1A),which has been shown to cause similar phenotypes when inactivated in PoMC-expressing cells.Our results indicate that developmental overexposure to thyroid hormone in PoMC-expressing cells programs energy balance mechanisms in a sexually dimorphic manner by suppressing adult hypothalamic BMPR1A expression.
文摘目的 :观察青年和老年期大鼠下丘脑弓状核阿黑皮素原 m RNA(POMC m RNA)的表达水平。 方法 :应用原位杂交技术显示 POMC m RNA和用计算机图像分析观察杂交信号的强弱及阳性细胞的面积。 结果 :与青年组相比 ,老年组下丘脑弓状核及其附近区域 POMC m RNA阳性神经元的平均灰度值下降 ;POMC m RNA阳性神经元的数目无明显变化。结论 :老年期 POMC m RNA阳性神经元相应的 m RNA表达水平下降可能是下丘脑 POMC基因衍生肽表达水平下降的原因之一。
基金supported by the National Natural Science Foundation of China(No.21677166)the National Key Research and Development Program of China(No.2018YFA0901103)。
文摘Fragmented data suggest that bisphenol AF(BPAF),a chemical widely used in a variety of products,might have potential impacts on the hypothalamus.Here,we employed male neonatal mice following maternal exposure to explore the effects of low-dose BPAF on hypothalamic development by RNA-sequencing.We found that maternal exposure to approximately 50μg/(kg·day)BPAF from postanal day(PND)0 to PND 15 altered the hypothalamic transcriptome,primarily involving the pathways and genes associated with extracellular matrix(ECM)and intercellular adhesion,neuroendocrine regulation,and neurological processes.Further RNA analysis confirmed the changes in the expression levels of concerned genes.Importantly,we further revealed that low-dose BPAF posed a stimulatory impact on pro-opiomelanocortin(POMC)neurons in the arcuate nucleus of the hypothalamus and induced the browning of inguinal white adipose tissue.All findings indicate that developmental exposure to low-dose BPAF could interfere with hypothalamic development and thereby lead to alterations in the metabolism.Interestingly,5000μg/(kg·day)BPAF caused slighter,non-significant or even inverse alterations than the low dose of 50μg/(kg·day),displaying a dose-independent effect.Further observations suggest that the the dose-independent effects of BPAF might be associated with oxidative stress and inflammatory responses caused by the high dose.Overall,our study highlights a risk of low-dose BPAF to human neuroendocrine regulation and metabolism.
基金Supported by 973 Program:the Research of Law and Principle of Moxibustion(No.2009CB522905)
文摘OBJECTIVE:To observe the influence of different moxibustion durations on hypothalamic pro-opiomelanocortin(POMC)and prodynorphin(PDYN)mRNA expressions and plasmaβ-endorphin(β-EP)content in rheumatoid arthritis(RA)rats,to understand the mechanism of moxibustion analgesia and its dose-effect relationship.METHODS:Twelve male Wistar rats were randomly selected from 48 male Wistar rats as a normal control group.The RA model was created by raising rats in a windy(blowing with electric fan),cold(6℃±2℃),and wet(80%-90%humidity)environment for 20 days,12 h each day.This was followed byinjectionofFreund'scompleteadjuvant(0.15 mL)into the ankle.Then,rats were randomly divided into a model group,moxibustion groupⅠ,and moxibustion groupⅡ,with 12 rats in each group.In moxibustion groupsⅠandⅡ,moxibustion was given at Shenshu(BL 23)and Zusanli(ST 36)for 20and 40 min,respectively,once daily for 15 days.Hypothalamic POMC and PDYN mRNA expression levels and plasmaβ-EP content were determined.RESULTS:Compared with the normal group,the pressure pain threshold decreased,while the hypothalamic POMC and PDYN mRNA expression levels and plasmaβ-EP content increased in the moxibustion groups(P<0.01).Compared with the model group,the pressure pain threshold,hypothalamic POMC and PDYN mRNA expression levels and plasmaβ-EP content in the moxibustion groups increased significantly(P<0.01).Compared the moxibustion groupⅠ,the pain threshold,hypothalamic POMC and PDYN mRNA expression levels and plasmaβ-EP content in moxibustion groupⅡsignificantly increased(P<0.01).CONCLUSION:Moxibustion has an analgesic effect and increases hypothalamic POMC and PDYN mRNA expression levels and plasmaβ-EP content inRArats.TheanalgesiceffectinmoxibustiongroupⅡisbetterthanthatinmoxibustiongroupⅠ.
