BACKGROUND：Leptin preserves reproductive functions by stimulating hypothalamic-pituitary-gonadal axis activities at different levels.Some interneurons play an important role in leptin regulation of the gonadal axis.I...BACKGROUND：Leptin preserves reproductive functions by stimulating hypothalamic-pituitary-gonadal axis activities at different levels.Some interneurons play an important role in leptin regulation of the gonadal axis.It remains uncertain whether leptin regulates reproductive functions by activating proopiomelanocortin （POMC） neurons.OBJECTIVE：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 points.DESIGN,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 2008.MATERIALS：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 study.METHODS：A total of 60 healthy,female,adult,Wistar rats received 17 （3-estradiol for 5 consecutive days at 15 days after ovariectomy.The rats were randomly assigned to physiological saline （n= 35）,leptin （n = 35）,and a-melanocyte stimulating hormone （n = 20） groups.MAIN 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 points.Changes in POMC mRNA and protein expression in the hypothalamus were measured following physiological saline and leptin injection via the lateral ventricle.RESULTS：Compared to the physiological saline group,leptin and a-melanocyte stimulating hormone affected secretion in the hypothalamus-pituitary axis.Leptin affected secretion of gonadotropin releasing hormone,luteinizing hormone,and follicle stimulating hormone,whereas a-melanocyte stimulating hormone inhibited secretion of these hormones.Compared to the physiological saline group,POMC mRNA expression was significantly increased in the hypothalamus at 2 and 4 hours after leptin injection （P〈 0.05）,but expression recovered to physiological saline group levels at 6 hours after injection （P 〉 0.05）.POMC protein expression was significantly increased in the hypothalamus at 4 and 6 hours after leptin injection （P〈 0.05）.CONCLUSION：Leptin affects secretory function of the neuroendocrine-gonadal axis through combined effects on POMC neurons and other pathways.Results suggested that the regulatory effects of POMC neurons were later compared to other neurons.展开更多
Alterations of proopiomelanocortin (POMC) rnRNA level in the hypothalamic arcuatenucleus were studied in rats grouped under 6h, 24h l 72h, 96h and 96h (EAX2 ) after elec-troacupuncture(EA) using rnolecular hybridizati...Alterations of proopiomelanocortin (POMC) rnRNA level in the hypothalamic arcuatenucleus were studied in rats grouped under 6h, 24h l 72h, 96h and 96h (EAX2 ) after elec-troacupuncture(EA) using rnolecular hybridization techniques. It was found that after EA, the levelof POMC mRNA rose significantly (P【0.001 ), a maximun being in the 72h group and declining inthe 96h group. In the 96h (EAX2 ) group, where EA was given at the beginning of the 72nd hour after the first one, instead of declining, the mRNA leve1 rose again. The findings may provide an expla-nation for the long postueffect of EA and its accumulation.展开更多
Objective Numerous schizophrenic patients are suffering from obesity primarily attributed to antipsychotic medication and poor dietary habits.This study investigated the progressive deterioration of olanzapine-induced...Objective Numerous schizophrenic patients are suffering from obesity primarily attributed to antipsychotic medication and poor dietary habits.This 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)stress.Methods 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 days.Changes in body weight,food intake,and plasma lipids were assessed.Hepatic fat accumulation was evaluated using oil red O staining.Western 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 liver.Results 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 expression.The 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 signaling.ER stress inhibitors could be effective in preventing olanzapine+HFD-induced metabolic disorders.展开更多
基金the Science Foundation of Hebei Provincial Science & Technology Department,No.08276101D-20the Science Foundation of Hebei Provincial Education Department,No. 2008301the Science and Technology Research and Development Project of Chengde City of Hebei Province,No. 200922061
文摘BACKGROUND：Leptin preserves reproductive functions by stimulating hypothalamic-pituitary-gonadal axis activities at different levels.Some interneurons play an important role in leptin regulation of the gonadal axis.It remains uncertain whether leptin regulates reproductive functions by activating proopiomelanocortin （POMC） neurons.OBJECTIVE：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 points.DESIGN,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 2008.MATERIALS：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 study.METHODS：A total of 60 healthy,female,adult,Wistar rats received 17 （3-estradiol for 5 consecutive days at 15 days after ovariectomy.The rats were randomly assigned to physiological saline （n= 35）,leptin （n = 35）,and a-melanocyte stimulating hormone （n = 20） groups.MAIN 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 points.Changes in POMC mRNA and protein expression in the hypothalamus were measured following physiological saline and leptin injection via the lateral ventricle.RESULTS：Compared to the physiological saline group,leptin and a-melanocyte stimulating hormone affected secretion in the hypothalamus-pituitary axis.Leptin affected secretion of gonadotropin releasing hormone,luteinizing hormone,and follicle stimulating hormone,whereas a-melanocyte stimulating hormone inhibited secretion of these hormones.Compared to the physiological saline group,POMC mRNA expression was significantly increased in the hypothalamus at 2 and 4 hours after leptin injection （P〈 0.05）,but expression recovered to physiological saline group levels at 6 hours after injection （P 〉 0.05）.POMC protein expression was significantly increased in the hypothalamus at 4 and 6 hours after leptin injection （P〈 0.05）.CONCLUSION：Leptin affects secretory function of the neuroendocrine-gonadal axis through combined effects on POMC neurons and other pathways.Results suggested that the regulatory effects of POMC neurons were later compared to other neurons.
文摘Alterations of proopiomelanocortin (POMC) rnRNA level in the hypothalamic arcuatenucleus were studied in rats grouped under 6h, 24h l 72h, 96h and 96h (EAX2 ) after elec-troacupuncture(EA) using rnolecular hybridization techniques. It was found that after EA, the levelof POMC mRNA rose significantly (P【0.001 ), a maximun being in the 72h group and declining inthe 96h group. In the 96h (EAX2 ) group, where EA was given at the beginning of the 72nd hour after the first one, instead of declining, the mRNA leve1 rose again. The findings may provide an expla-nation for the long postueffect of EA and its accumulation.
基金the Natural Science Foundation of Hubei Province(No.2021CFB301 and No.2021CFB299)the State Key Laboratory of Advanced Technology for Materials Synthesis and Processing(WUT)(No.2022-KF-27).
文摘Objective Numerous schizophrenic patients are suffering from obesity primarily attributed to antipsychotic medication and poor dietary habits.This 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)stress.Methods 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 days.Changes in body weight,food intake,and plasma lipids were assessed.Hepatic fat accumulation was evaluated using oil red O staining.Western 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 liver.Results 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 expression.The 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 signaling.ER stress inhibitors could be effective in preventing olanzapine+HFD-induced metabolic disorders.
