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Leptin: a multifunctional hormone

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Cell Research 2000年第2期10卷 81-92页

作者： HUANG Lu, CAI LI(Tel: (214)-648-3340 Fax: (214)-648-9191 E-mail: li03@utsw.swmed.edu)(1 Touchstone Center for Diabetes Research1 Departments of Physiology and,2 Departments of Internal MedicineThe University of Texas Southwestern Medical Center5323 H. Touc hstone Center for Diabetes Research The University of Texas Southwestern Medical Center 5323 H. Hines Boulevard Dallas USA Departments of Physiology The University of Texas Southwestern Medical Center 5323 H. Hines Boulevard Dallas USA Department of Internal Medicine The University of Texas Southwestern Medical Center 5323 H. Hines Boulevard Dallas USA

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.

关键词： Leptin OB-R hypothalamus adipose tissue obesity diabetes cytokine receptor

A Brain-Spleen Axis Regulates Humoral Immunity

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Neuroscience Bulletin 2021年第3期37卷 427-429页

作者： Bin Zhang Jinjie Zhong Zhihua Gao Neuroscience Research Center and Department of Neurology The Second Affiliated HospitalKey Laboratory of Medical Neurobiology of Zhejiang ProvinceSchool of Brain Science and Brain MedicineZhejiang UniversityHangzhou 310058China School of Basic Medical Sciences Zhejiang UniversityHangzhou 310058China

A happy mood helps to build a flourishing immune system.Interactions between the nervous and immune systems have attracted the interest of researchers for decades.It is well known that external stressors can activate the hypothalamus to regulate immune responses via the hypothalamic-pituitary-adrenal cortex(HPA)axis[1].As well,inflammatory stimuli can activate a rapid antiinflammatory reflex via the cholinergic vagus nerve pathway.

关键词： cortex Spleen hypothalamus

Functional magnetic resonance imaging and immunohistochemical study of hypothalamic function following oral glucose ingestion in rats

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Chinese Medical Journal 2007年第14期120卷 1232-1235页

作者： CHEN Min ZHANG Tie-mei LUO Sen-lin ZHOU Cheng WU Xiao-meng ZHOU Ni-na CAI Kui YANG Zhen-han WANG Wen-chao ZHAO Wei-feng LI Sa-ying WANG Zhi ZHANG Yun-ting LI Guo-zhen Department of Radiology Beijing Hospital Beijing 100730 China Department of Cytology Beijing Institute of Geriatrics Beijing 100730 China Beijing Institute of Technology Beijing 100034 China Tianjin Medical University Tianjin 300070 China

Background The hypothalamus plays a central role in the regulation of metabolism by sensing metabolic demands and releasing regulatory neurotransmitters. This study investigated the response of the hypothalamus to glucose ingestion in rats by blood oxygen level-dependent functional magnetic resonance imaging （BOLD-fMRI） and immunohistochemical techniques to determine the role of the hypothalamus in glycoregulation during disturbances in carbohydrate metabolism. Methods The signal intensity of the hypothalamus was monitored by fMRI for 60 minutes after oral glucose intake in 48 healthy rats （age 14 months）, which included 24 normal weight rats （weighing （365±76.5） g） and 24 overweight rats （weighing （714±83.5） g）. Then, 12 rats （6 normal, 6 overweight） underwent a repeat fMRI scan after consuming an equivalent amount of water without glucose on a separate day. The procedure for fMRI with water intake was the same as for glucose ingestion, fMRI data was processed using time cluster analysis and intensity averaging method. After fMRI the expression of neuropeptide Y （NPY） and 5-hydroxytryptamine （5-HT） in the hypothalamus of all rats was determined by immunohistochemistry. Positive cells for NPY or 5-HT were counted. Results There was a transient, but significant, decrease in fMRI signal intensity in all rats （mean （3.12±0.78）%） in the hypothalamus within 19.5-25.5 minutes of oral glucose ingestion. In overweight rats, the decrease in signal intensity in response to the glucose ingestion was more markedly attenuated than that observed in normal weight rats （（2.2±1.5）% vs （4.2±0.7）% inhibition, t=2.12, P〈0.05）. There was no significant response in the hypothalamus after oral water ingestion. The percentage of NPY positive cells in obese rats were slightly lower than those in control group （21% vs 23% t=0.71, P〉0.05）; but there was no significant difference between the two groups; the percentage of 5-HT positive cells in obese rats were significantly lower than those in the control group （22% vs 31%, t=3.25, P〈0.0

关键词： functional magnetic resonance imaging hypothalamus glucose neuropeptide Y serotonin

Regeneration of neurotransmission transcriptome in a model of epileptic encephalopathy after antiinflammatory treatment

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Neural Regeneration Research 2018年第10期13卷 1715-1718页

作者： Dumitru A.Iacobas Libor Velísek Center for Computational Systems Biology Prairie View AM University Prairie View TX USA D.P.Purpura Department of Neuroscience Albert Einstein College of MedicineNew York NY USA Department of Cell Biology & Anatomy New York Medical CollegeValhalla NY USA Department of Neurology New York Medical CollegeValhalla NY USA Department of Pediatrics New York Medical CollegeValhalla NY USA

Inflammation is an established etiopathogenesis factor of infantile spasms（IS）, a therapy-resistant epileptic syndrome of infancy. We investigated the IS-associated transcriptomic alterations of neurotransmission in rat hypothalamic arcuate nucleus, how they are corrected by antiinflamatory treatments and whether there are sex differences. IS was triggered by repeated intraperitoneal administration of N-methyl-D-aspartic acid following anti-inflammatory treatment（adreno-cortico-tropic-hormone（ACTH） or PMX53）or normal saline vehicle to prenatally exposed to betamethasone young rats. We found that treatments with both ACTH and PMX53 resulted in substantial recovery of the genomic fabrics of all types of synaptic transmission altered by IS. While ACTH represents the first line of treatment for IS, the even higher efficiency of PMX53（an antagonist of the complement C5 a receptor） in restoring the normal transcriptome was not expected. In addition to the childhood epilepsy, the recovery of the neurotransmission genomic fabrics by PMX53 also gives hope for the autism spectrum disorders that share a high comorbidity with IS. Our results revealed significant sex dichotomy in both IS-associated transcriptomic alterations（males more affected） and in the efficiency of PMX53 anti-inflammatory treatment（better for males）. Our data further suggest that anti-inflammatory treatments correcting alterations in the inflammatory transcriptome may become successful therapies for refractory epilepsies.

关键词： adreno-cortico-tropic-hormone autism cholinergic transmission hypothalamus infantile spasms microarrays PMX53 sex differences

Effects of “Bioactive” amino acids leucine, glutamate, arginine and tryptophan on feed intake and mRNA expression of relative neuropeptides in broiler chicks

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Journal of Animal Science and Biotechnology 2012年第4期3卷 199-206页

作者： Songbo Wang Paul Khondowe Shengfeng Chen Jianjian Yu Gang Shu Xiaotong Zhu Lina Wang Ping Gao Qianyun Xi Yongliang Zhang Qingyan Jiang College of Animal Sciences South China Agricultural University School of Natural Sciences Department of Biological SciencesUniversity of Zambia

Feed intake control is vital to ensuring optimal nutrition and achieving full potential for growth and development in poultry. The aim of the present study was to investigate the effects of L-leucine, L-glutamate, L-tryptophan and L-arginine on feed intake and the mRNA expression levels of hypothalamic Neuropeptide involved in feed intake regulation in broiler chicks. Leucine, glutamate, tryptophan or arginine was intra-cerebroventricularly （ICV） administrated to 4d-old broiler chicks respectively and the feed intake were recorded at various time points. Quantitative PCR was performed to determine the hypothalamic mRNA expression levels of Neuropeptide Y （NPY）, agouti related protein （AgRP）, pro-opiomelanocortin （POMC）, melanocortin receptor 4 （MC4R） and corticotrophin releasing factor （CRF）. Our results showed that ICV administration of L-leucine （0.15 or 1.5 μmol） significantly （P〈0.05） increased feed intake up to 2 h post-administration period and elevated both hypothalamic NPY and AgRP mRNA expression levels. In contrast, ICV administration of L-glutamate （1.6 μmol） significantly （P 〈 0.05） decreased feed intake 0.25, 0.5 and 2 h post-injection, and increased hypothalamic CRF and MC4R mRNA expression levels. Meanwhile, both L-tryptophan （10 or 100 μg） and L-arginine （20 or 200 μg） had no significant effect on feed intake. These findings suggested that L-leucine and L-glutamate could act within the hypothalamus to influence food intake, and that both orexigenic and anorexigenic Neuropeptide genes might contribute directly to these effects.

关键词： Broiler chicks Feed intake hypothalamus Intracerebroventricular （ICY） L-leucine L-glutamate

The role of central nervous system on hypoglycemia and the feasibility of the brain theory in traditional Chinese medicine on treatment of diabetes mellitus

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Journal of Integrative Medicine 2014年第1期12卷 1-6页

作者： Hai-li Jiang Jing-jing Niu Wei-fei Zhang Wen-jin Huang Ming-yue Zhou Wen-jun Sha Jun-yan Li Fu-feng Li Ting Zhu Xin Xia Jun Zhang Yuan-dong Shen Li-gang Zhou Department of Endocrinology Shanghai Pudong HospitalFudan University Pudong Medical Center Department of Endocrinology Shuguang HospitalShanghai University of Traditional Chinese Medicine Diabetes Research Center Shanghai University of Traditional Chinese Medicine Basic Medical Department Shanghai University of Traditional Chinese Medicine Biology and Biological Science Program University of California Department of Gerontology Shuguang HospitalShanghai University of Traditional Chinese Medicine Department of Endocrinology Shanghai East Hospital Department of Police Training Shanghai Police College

The central nervous system （CNS） plays a key regulatory role in glucose homeostasis. In particular, the brain is important in initiating and coordinating protective counterregulatory responses when blood glucose levels fall. This may due to the metabolic dependency of the CNS on glucose, and protection of food supply to the brain. In healthy subjects, blood glucose is normally maintained within a relatively narrow range. Hypoglycemia in diabetic patients can increase the risk of complications, such as heart disease and diabetic peripheral neuropathy. The clinical research finds that the use of traditional Chinese medicine （TCM） has a positive effect on the treatment of hypoglycemia. Here the authors reviewed the current understanding of sensing and counterregulatory responses to hypoglycemia, and discuss combining traditional Chinese and Western medicine and the theory of iatrogenic hypoglycemia in diabetes treatment. Furthermore, the authors clarify the feasibility of treating hypoglycemia on the basis of TCM theory and CNS and have an insight on its clinical practice.

关键词： diabetes mellitus hypoglycemia counterrugulation hormone response neuroendocrine systems hypothalamus brain review

Diffuse large B cell lymphoma with bilateral adrenal and hypothalamic involvement: A case report and literature review

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World Journal of Clinical Cases 2019年第23期7卷 4075-4083页

作者： Ping An Kang Chen Guo-Qing Yang Jing-Tao Dou Yu-Long Chen Xin-Ye Jin Xian-Ling Wang Yi-Ming Mu Quan-Shun Wang Department of Endocrinology Chinese PLA General HospitalBeijing 100853China Department of Hematology Chinese PLA General HospitalBeijing 100853China

BACKGROUND Non-Hodgkin’s lymphoma(NHL)can involve extralymphatic organs,resulting in diverse clinical manifestations,especially if the endocrine organs are affected.This type of involvement can often be difficult to detect accurately.Until now,no patients with NHL and concomitant bilateral adrenal and hypothalamic involvement have been reported.The purpose of this article is to discuss the diagnosis and treatment of lymphoma with bilateral adrenal gland and hypothalamic involvement so as to help physicians avoid misdiagnosis and missed diagnosis.CASE SUMMARY We describe a case of a 52-years-old male patient with bilateral adrenal masses,who presented with a fever of unknown origin on admission.Subsequently,hypopituitarism of the anterior pituitary followed by posterior pituitary developed.18fluorine-fluorodeoxyglucose positron emission tomography/computed tomography(PET/CT)showed lesions with a high metabolism in both adrenal glands,hypothalamus,left supraclavicular lymph nodes,and other organs.The etiological diagnosis was determined based on a left supraclavicular lymph node biopsy.The patient,who eventually present with panhypopituitarism,was finally diagnosed with diffuse large B cell lymphoma with bilateral adrenal gland and hypothalamic involvement.After immunochemotherapy,glucocorticoids administration and desmopressin acetate replacement therapy,the symptoms of fever and panhypopituitarism improved,and all the lesions reduced in size.CONCLUSION This report demonstrates that,although synchronous involvement of two endocrine organs is rare in NHL,extra caution should be taken when dysfunction occurs in multiple endocrine organs.

关键词： Non-Hodgkin’s lymphoma Bilateral adrenal glands hypothalamus Panhypopituitarism Case report

Xiaoyaosan decoction regulates food intake and body weight via the leptin-leptin receptor-proopiomelanocortin pathway in rats with chronic immobilization stress

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Journal of Traditional Chinese Medicine 2019年第1期39卷 34-44页

作者： Wang Xia Fang Chaoyi Wu Jiaxin Wang Shaoxian Zhao Runsheng Ma Jinsheng School of Preclinical Medicine Hebei University of Chinese MedicineShijiazhuang 050200China.

OBJECTIVE: To evaluate the effects of the Xiaoyaosan(XYS) decoction on the food intake and body weight of rats with chronic immobilization stress(CIS), as well as the concentration of serum leptin and the expression of feeding-related neuropeptides [leptin receptor(Ob-R), proopiomelanocortin(POMC), and α-melanocyte-stimulating hormone(α-MSH)] in the hypothalamic arcuate nucleus(ARC).METHODS: We subjected rats to CIS for 3 h a day.The rats were randomly divided into the following groups: control group, 7-day stress group, 21-day stress group and XYS-treated group. The rats in the two stress groups were exposed to CIS for 7 or 21 d.The rats in the XYS-treated group were also exposed to CIS for 21 d and were intragastrically administered the XYS decoction before stress. The body weight and food intake of the rats were measured every day. The content of leptin in serum andα-MSH in the ARC were detected by ELISA, and the expression of neuropeptides in the ARC was assayed by immunofluorescence, Western blot and q RT-PCR.RESULTS: The food intake and body weight of rats exposed to CIS were lower than those of control rats. The serum leptin, and expression levels of ObR, POMC and α-MSH in the ARC were significantly higher than those in the control rats. Treatment with the XYS decoction improved the appetite and the body weight, and down-regulated serum leptin and Ob-R, POMC and α-MSH in hypothalamus ARC.CONCLUSION: The leptin-Ob-R-POMC pathway might be the part of the mechanism underlying XYS's improvement of somatic symptoms such as reduction in food intake and body weight related to CIS.

关键词： Chronic immobilization stress Xiao Yao San Neuropeptides Arcuate nucleus of hypothalamus Eating

High on food： the interaction between the neural circuits for feeding and for reward

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Frontiers in Biology 2015年第2期10卷 165-176页

作者： Jing-Jing Liu Diptendu Mukherjee Doron Haritan Bogna Ignatowska-Jankowska Ji Liu Ami Citri Zhiping P. Pang Child Health Institute of New Jersey Department of Neuroscience and Cell Biology Rutgers University Robert Wood Johnson Medical School New Brunswick NJ 08901 USA Department of Biological Chemistry Institute for Life Sciences The Hebrew University of Jerusalem 91904 Jerusalem Israel The Edmond and Lily Safra Center for Brain Sciences The Hebrew University of Jerusalem 91904 Jerusalem Israel

Hunger, mostly initiated by a deficiency in energy, induces food seeking and intake. However, the drive toward food is not only regulated by physiological needs, but is motivated by the pleasure derived from ingestion of food, in particular palatable foods. Therefore, feeding is viewed as an adaptive motivated behavior that involves integrated communication between homeostatic feeding circuits and reward circuits. The initiation and termination of a feeding episode are instructed by a variety of neuronal signals, and maladaptive plasticity in almost any component of the network may lead to the development of pathological eating disorders. In this review we will summarize the latest understanding of how the feeding circuits and reward circuits in the brain interact. We will emphasize communication between the hypothalamus and the mesolimbic dopamine system and highlight complexities, discrepancies, open questions and future directions for the field.

关键词： feeding neural circuitry hedonic reward mesolimbic system dopamine hypothalamus