Essential amino acids(EAAs)are crucial nutrients,whose levels change in rodents and patients with depression.However,how the levels of a single EAA affects depressive behaviors remains elusive.Here,we demonstrate that...Essential amino acids(EAAs)are crucial nutrients,whose levels change in rodents and patients with depression.However,how the levels of a single EAA affects depressive behaviors remains elusive.Here,we demonstrate that although deprivation of the EAA leucine has no effect in unstressed mice,it remarkably reverses the depression-like behaviors induced by chronic restraint stress(CRS).This beneficial effect is independent of feeding and is applicable to the dietary deficiency of other EAAs.Furthermore,the effect of leucine deprivation is suppressed by central injection of leucine or mimicked by central injection of leucinol.Moreover,hypothalamic agouti-related peptide(AgRP)neural activity changes during CRS and leucine deprivation,and chemogenetically inhibiting AgRP neurons eliminates the antidepressant effects of leucine deprivation.Finally,the leucine deprivation-regulated behavioral effects are mediated by amino acid sensor general control non-derepressible 2(GCN2)in AgRP neurons.Taken together,our results suggest a new drug target and/or dietary intervention for the reduction of depressive symptoms.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
The physiology and behaviors related to energy balance are monitored by the nervous and humoral systems. Because of the difficulty in treating diabetes and obesity, elucidating the energy balance mechanism and identif...The physiology and behaviors related to energy balance are monitored by the nervous and humoral systems. Because of the difficulty in treating diabetes and obesity, elucidating the energy balance mechanism and identifying critical targets for treatment are important research goals. Therefore, the purpose of this article is to describe energy regulation by the central nervous system(CNS) and peripheral humoral pathway. Homeostasis and rewarding are the basis of CNS regulation. Anorexigenic or orexigenic effects reflect the activities of the POMC/CART or NPY/AgRP neurons within the hypothalamus. Neurotransmitters have roles in food intake, and responsive brain nuclei have different functions related to food intake, glucose monitoring, reward processing. Peripheral gut-or adipose-derived hormones are the major source of peripheral humoral regulation systems. Nutrients or metabolites and gut microbiota affect metabolism via a discrete pathway. We also review the role of peripheral organs, the liver,adipose tissue, and skeletal muscle in peripheral regulation. We discuss these topics and how the body regulates metabolism.展开更多
基金This work was supported by the National Natural Science Foundation of China(31830044,91957207,81870592,82270905,81970742,82000764,82170868,and 81970731)The National Key R&D Program of China(grant 2018YFA0800600).
文摘Essential amino acids(EAAs)are crucial nutrients,whose levels change in rodents and patients with depression.However,how the levels of a single EAA affects depressive behaviors remains elusive.Here,we demonstrate that although deprivation of the EAA leucine has no effect in unstressed mice,it remarkably reverses the depression-like behaviors induced by chronic restraint stress(CRS).This beneficial effect is independent of feeding and is applicable to the dietary deficiency of other EAAs.Furthermore,the effect of leucine deprivation is suppressed by central injection of leucine or mimicked by central injection of leucinol.Moreover,hypothalamic agouti-related peptide(AgRP)neural activity changes during CRS and leucine deprivation,and chemogenetically inhibiting AgRP neurons eliminates the antidepressant effects of leucine deprivation.Finally,the leucine deprivation-regulated behavioral effects are mediated by amino acid sensor general control non-derepressible 2(GCN2)in AgRP neurons.Taken together,our results suggest a new drug target and/or dietary intervention for the reduction of depressive symptoms.
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 the National Natural Science Foundation of China (81370932)the United States MERCK IISP Fund (40313, 40309)+2 种基金Outstanding Leaders Training Program of Pudong Health Bureau of Shanghai (PWR12014-06)Integrative Medicine special fund of Shanghai Municipal Health Planning Committee (ZHYY-ZXYJHZX2-201712)the Key Studies (Special) Department Fund of the Pudong New Area Health Planning Commission (PWZzk2017-03)
文摘The physiology and behaviors related to energy balance are monitored by the nervous and humoral systems. Because of the difficulty in treating diabetes and obesity, elucidating the energy balance mechanism and identifying critical targets for treatment are important research goals. Therefore, the purpose of this article is to describe energy regulation by the central nervous system(CNS) and peripheral humoral pathway. Homeostasis and rewarding are the basis of CNS regulation. Anorexigenic or orexigenic effects reflect the activities of the POMC/CART or NPY/AgRP neurons within the hypothalamus. Neurotransmitters have roles in food intake, and responsive brain nuclei have different functions related to food intake, glucose monitoring, reward processing. Peripheral gut-or adipose-derived hormones are the major source of peripheral humoral regulation systems. Nutrients or metabolites and gut microbiota affect metabolism via a discrete pathway. We also review the role of peripheral organs, the liver,adipose tissue, and skeletal muscle in peripheral regulation. We discuss these topics and how the body regulates metabolism.
