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Leptin effects on the hypothalamic-pituitary-gonadal axis by activating proopiomelanocortin neurons Correlation between regulatory effects and duration

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Neural Regeneration Research 2010年第9期5卷 715-719页

作者： Songhe Yang Luyang Cheng Xiuyan Ma Lianzhi Zhao Xiaotong Dong Peiming Feng Xiaoqiang Wang Tiecheng Sun Yuebing Qiao Chengde Medical University Chengde 067000 Hebei Province China Affiliated Hospital of Chengde Medical University Chengde 067000 Hebei Province China Postgraduate School Peking Union Medical College Beijing 100730 China

BACKGROUND：Leptin preserves reproductive functions by stimulating hypothalamic-pituitary-gonadal axis activities at different *** interneurons play an important role in leptin regulation of the gonadal *** remains uncertain whether leptin regulates reproductive functions by activating proopiomelanocortin （POMC） ***：To investigate leptin effects on secretory function of the neuroendocrine-gonadal axis by activating POMC neurons and to observe and verify the relationship between leptin effects and various time ***,TIME AND SETTING：The randomized,controlled,animal study was performed at the Basic Institute of Chengde Medical University and the Research Room of Reproductive Immunology of National Research Institute for Family Planning from June to September ***：Leptin （Peprotech,USA）,a-melanocyte stimulating hormone and rabbit anti-POMC polyclonal antibody （SC-20148）（Santa Cruz Biotechnology,USA）,follicle stimulating hormone,luteinizing hormone,and gonadotropin releasing hormone enzyme-labeled immunosorbent assay （ELISA） kit （ADL,USA） were used in the present ***：A total of 60 healthy,female,adult,Wistar rats received 17 （3-estradiol for 5 consecutive days at 15 days after *** rats were randomly assigned to physiological saline （n= 35）,leptin （n = 35）,and a-melanocyte stimulating hormone （n = 20） *** OUTCOME MEASURES：Changes in gonadotropin releasing hormone,luteinizing hormone,and follicle stimulating hormone were compared following intraventricular injection of physiological saline,leptin,and a-melanocyte stimulating hormone at various time *** in POMC mRNA and protein expression in the hypothalamus were measured following physiological saline and leptin injection via the lateral ***：Compared to the physiological saline group,leptin and a-melanocyte stimulating hormone affected secretion in the hypothalamus-pituitary *** affected secretion of gonadotropin rel

关键词： lateral ventricle leptin a-melanocyte stimulating hormone neuroendocrine-gonadal axis ovariectomy proopiomelanocortin

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HFD-exacerbated Metabolic Side Effects of Olanzapine Are Suppressed by ER Stress Inhibitor

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Current Medical Science 2023年第6期43卷 1116-1132页

作者： Yu-feng ZUO Bao-hua ZHANG Ming-rui GUO Ben-ben LI Bao-cui WANG Deng DUAN Yu-xin WANG Jing XI Meng HE Tao-lei SUN School of Chemistry Chemical Engineering and Life SciencesWuhan University of TechnologyWuhan430070China The National Clinical Research Center for Mental Disorders&Beijing Key Laboratory of Mental Disorders Beijing Anding Hospital&the Advanced Innovation Center for Human Brain ProtectionCapital Medical UniversityBeijing100069China Hubei Key Laboratory of Nanomedicine for Neurodegenerative Diseases School of ChemistryChemical Engineering and Life ScienceWuhan University of TechnologyWuhan430070China

Objective Numerous schizophrenic patients are suffering from obesity primarily attributed to antipsychotic medication and poor dietary *** study investigated the progressive deterioration of olanzapine-induced metabolic disorders in the presence of a high-fat diet(HFD)and explored the involvement of endoplasmic reticulum(ER)*** Female Sprague-Dawley rats fed on a standard chow diet or HFD were treated with olanzapine(3 mg/kg/day)and the ER stress inhibitor 4-phenylbutyric acid(4-PBA,1 and 0.5 g/kg/day)for 8 *** in body weight,food intake,and plasma lipids were *** fat accumulation was evaluated using oil red O *** blotting and immunofluorescence assays were employed to examine the expression of ER stress markers,NOD-like receptor pyrin domain-containing protein 3(NLRP3),and proopiomelanocortin(POMC)in the hypothalamus or *** Compared to olanzapine alone,olanzapine+HFD induced greater weight gain,increased hyperlipidemia,and enhanced hepatic fat accumulation(P<0.05).Co-treatment with 4-PBA exhibited a dose-dependent inhibition of these effects(P<0.05).Further mechanistic investigations revealed that olanzapine alone activated ER stress,upregulated NLRP3 expression in the hypothalamus and liver,and downregulated hypothalamic POMC *** HFD exacerbated these effects by 50%–100%.Moreover,co-administration of 4-PBA dose-dependently attenuated the olanzapine+HFD-induced alterations in ER stress,NLRP3,and POMC expression in the hypothalamus and liver(P<0.05).Conclusion HFD worsened olanzapine-induced weight gain and lipid metabolic disorders,possibly through ER stress-POMC and ER stress-NLRP3 *** stress inhibitors could be effective in preventing olanzapine+HFD-induced metabolic disorders.

关键词： olanzapine high-fat diet obesity lipid metabolism endoplasmic reticulum stress proopiomelanocortin NOD-like receptor pyrin domain-containing protein 3

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Characteristics of ectopic adrenocorticotropic hormone syndrome due to thymic carcinoid and analysis of the molecular mechanism

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Chinese Medical Journal 2008年第7期121卷 667-670页

作者： BI Yu-fang YE Lei CHEN Yu-hong NING Guang SUN Shou-yue JIANG Lei ZHU Na ZHOU Wei-wei WANG Wei-qing Department of Endocrinology and Metabolism Shanghai ClinicalCenter for Endocrine and Metabolic Diseases Shanghai Instituteof Endocrine and Metabolic Diseases Ruijin Hospital ShanghaiJiao Tong University School of Medicine Shanghai 200025 China

Ectopic adrenocorticotropic hormone （ACTH） secretion rfrom a non-pituitary tumor is a main cause of Cushing＇s syndrome, which is associated with significant morbidity and mortality. Although early studies showed that the predominant cause of ectopic Cushing＇s syndrome is small cell carcinomas of the lungs, the incidence of carcinoid, including thymic carcinoid, has increased substantially in recent surveys） This evidence suggested that the clinical syndrome of ectopic ACTH production only occurs in tumors with high proopiomelanocortin （POMC, the precursor to ACTH） transcripts generated from the start of the pituitary transcription initiation site.2

关键词： ectopic A CTH syndrome Cushing's syndrome thymic tumor proopiomelanocortin

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The effect of traditional Chinese medicine──Tian Gui Recipeon obesity and anovulation in androgen-sterilized rats

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生殖医学杂志 2000年第S1期9卷 26-33页

作者：俞瑾孙斐

Objective: A traditional Chinese medicine Tian Gui Recipe (TGR) has been used to effectively treat clomiphene resistant anovulatory disease and obesity, especially in polycystic ovary syndrome (PCOS) cases with hyperinsulinemia. The effect of TGR on obesity and anovulation was investigated in androgen-sterilized rats (ASR). Methods: Female SD rats at the age of 9 days were divided into 3 groups. Group ASR (n=15): anovulation was demonstrated at the age of 70 days by vaginal smear in rats while 1. 25 mg of testosterone propionate was injected subcutaneously on its 9th neonatal day. Group A+H (n = 25): TGR were administered to ASR at the age of 80 days for 3 weeks. Rats with regular estrous cycle and ovulation after herbal treatment were included in this group. Group C (n = 15): normal ovulated rats were recruited. Around the age of 112 days or on proestrous day, all rats were sacrificed under anesthesia. Serum leptin, testosterone (T), estrogen (E2), follicular stimulating hormone (FSH), luteinizing hormone (LH) levels were measured with radioimmunoassay (RIA). Double immunofluorescent staining combined with confocal laser scanning microscope and dual in situ hybridization were carried out on sections through areas of arcuate nucleus (ARC) to determine whether estrogen receptor (ER) immunoreactivity (IR) or long form of leptin receptor (OB-Rb) mRNA were expressed in neuropeptide Y (NPY) immuno-and mRNA-containing neurons, and its relationship to proopiomelanocortin (POMC) mRNA-containing neurons. Immunohistochemistry and in situ hybridization were used to observe the levels of ER, NPY, gonadotrophin releasing hormone (GnRH) and gene expression levels on NPY, OB-Rb, POMC. Meanwhile, the criteria of energy state, including daily food intake, retroperitoneal fat depot pad and body weight, were measured and evaluated. Values of immunohistochemistry and in situ hybridization were expressed in mean optic density (MOD). Results: Seventeen out of the 25 rats (68%) in Group A

关键词： Androgen-sterilized rat, Traditional Chinese medicine Neuropeptide Y Leptin proopiomelanocortin Estrogen Gonadotrophin releasing hormone Immunohistochemistry In situ hybridization mRNA This work was supported by a grant from the Planni

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The effect of traditional Chinese medicine“Tian Gui Recipe (TGR)”on obesity and anovulation in androgen-sterilized rats(ASR)

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生殖医学杂志 2002年第Z1期11卷 13-21页

作者： Yu Jin(俞瑾) Sun Fei(孙斐) Obstetrics and Gynecology Hospital Medical Centre of Fudan University Shanghai 200011 Obstetrics and Gynecology Hospital Medical Centre of Fudan University Shanghai 200011

Objectives: A traditional Chinese medicine “Tian Gui Recipe (TGR)” has been used to effectively treat clomiphene resistant anovulatory disease and obesity, especially in polycystic ovary syndrome (PCOS) cases with hyperinsulinemia. The effect of TGR on obesity and anovulation was investigated in androgen-sterilized rats (ASR).Methods: Female SD rats at the age of 9 days were divided into 3 groups. Group ASR (n=15): anovulation was demonstrated at the age of 70 days by vaginal smear in rats while 1.25 mg of testosterone propionate was injected subcutaneously on its 9th neonatal day. Group A+H (n=25): TGR were administered to ASR at the age of 80 days for 3 weeks. Rats with regular estrous cycle and ovulation after herbal treatment were included in this group. Group C (n=15): normal ovulated rats were recruited. Around the age of 112 days or on proestrous day, all rats were sacrificed under anesthesia. Serum leptin, testosterone (T), estrogen (E2), follicular stimulating hormone (FSH), luteinizing hormone (LH) levels were measured with radioimmunoassay (RIA). Double immunofluorescent staining combined with confocal laser scanning microscope and dual in situ hybridization were carried out on sections through areas of arcuate nucleus (ARC) to determine whether estrogen receptor (ER) immunoreactivity (IR) or long form of leptin receptor (OB-Rb) mRNA were expressed in neuropeptide Y (NPY) immuno- and mRNA-containing neurons, and their relationship to proopiomelanocortin (POMC) mRNA-containing neurons. Immunohistochemistry and in situ hybridization were used to observe the levels of ER-, NPY-,gonadotrophin releasing hormone (GnRH)-IR and gene expression levels of NPY, OB-Rb, and POMC in ARC. Meanwhile, the criteria of energy state,including daily food intake, retroperitoneal fat depot pad and body weight,were measured and evaluated. Values of immunohistochemistry and in situ hybridization were expressed in mean optic density (MOD).Results:Seventeen out of the 25 rats (68%)

关键词： Androgen-sterilized rat Traditional chinese medicine Neuropeptide Y Leptin Long form of leptin receptor proopiomelanocortin Estrogen Estrogen receptor Gonadotrophin releasing hormone Double immunohistochemistry Dual in situ hybridization mRNA

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The Mechanism of Regulating Leptin Resistance in Obesity and the Influence of Adjusting Methylation of OB-R,POMC Gene Promoter of Wendan Decoction (温胆汤)

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World Journal of Integrated Traditional and Western Medicine 2020年第6期6卷 23-30页

作者： YANG Hai-yan YU Song-ren WANG Ping SHU Qing CHENG Shao-min Science and Technology College Jiangxi University of traditional Chinese MedicineNanchang 330000China College of Traditional Chinese Medicine Jiangxi University of traditional Chinese MedicineNanchang 330000China Graduate student of Jiangxi University of traditional Chinese Medicine Nanchang 330000China

Objective:To explore the mechanism of Wendan Decoction(温胆汤)regulating leptin resistance in obesity by analyzing the level of leptin in peripheral blood,the expression of leptin receptor and signal pathway molecule POMC in *** analyze the methylation status of the gene promoters of leptin receptor and POMC in obese rats fed with high fat diet,and the influence of adjusting methylation of OB-R,POMC gene promoter about Wendan ***:Model rats were randomly divided into model control group and drug observation group,additional normal rats with 8 rats in each *** models were established by high fat *** observation group was treated with Wendan Decoction(温胆汤)and the other two groups were treated with sterilized drinking water once a day for 6 *** weight was recorded every week during the *** blood and hypothalamus were collected at the end of the *** serum leptin level was measured by ELISA method,and the expression of OB-R and POMC in hypothalamus was detected by RT-qPCR *** level of OB-R and POMC promoter detected by methylation specific ***:Our results revealed that Wendan Decoction(温胆汤)could effectively reduce body weight,the body weight in the drug observation group was significantly lower than that in the model control group,and the difference between the two groups was statistically *** level of leptin in peripheral blood and the expression of OB-R in hypothalamus were consistent with the trend of body *** heavier the weight,the higher the level of leptin and *** Decoction(温胆汤)could reduce the level of leptin and OB-R in peripheral blood while reducing body *** with the model control group,the difference was statistically *** heavier the weight,the lower the level of POMC *** Decoction(温胆汤)could increase the expression of POMC while reducing body weight,which had statistical significance compared with the m

关键词： Wendan Decoction(温胆汤) proopiomelanocortin Obesity Leptin resistance Methylation

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