Obesity
·
2015
·Vol. 24
·期 2
·368-378
·
IF 3.734
Ziquan Lv,Jinquan Cheng,Suli Huang,Yanwei Zhang,Shuang Wu,Yangshen Qiu,Yijie Geng,Qian Zhang,Guanqin Huang,Quan Ma,Xing Xie,Shiquan Zhou,Tangchun Wu,Yuebin Ke
Objective Di(2-ethylhexyl) phthalate (DEHP) is reported to cause obesity and hypothyroidism in both humans and rodents, but the underlying mechanisms were largely unknown. This study was designed to clarify the effects and the mechanisms of DEHP on the pathogenesis of obesity and hypothyroidism and to discover the relationship between them. Methods Male C3H/He mice were treated with DEHP for 5 weeks, and the body weight, food intake, and body temperature were recorded during the exposure. After exposure, key organs and serum were analyzed by Q-PCR, Western blot, and ELISA. Results DEHP induced significant body weight gain and adipogenesis in all exposure groups except for 0.05 mg/kg. Marked hyperphagia and daytime hypothermia were also observed, which were accompanied by disturbed hypothalamic neuropeptide expression and reduced BAT UCP1 expression. In addition, WAT lipid metabolism was significantly deceased at low dose (0.5 mg/kg) and increased at high dose (50 and 200 mg/kg). DEHP also induced hypothyroidism, which was probably attributed to the combined effects of hepatic CAR activation and hypothalamic TRH inhibition induced by hypothalamic leptin resistance. Conclusions Chronic DEHP exposure could induce obesity by interrupting energy homeostasis, which is probably due to the synergistic effects of hypothyroidism and hypothalamic leptin resistance.
研究领域:
毒理学
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内分泌学
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代谢
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产品关联
DOI
PubMed
高影响因子
TALANTA
·
2025
·
IF 6.1
Jiameng Pei,Lina Tang,Chenyang Kang,Fan Shi,Fengxia Liang,Yutao Li,Guo-Jun Zhang
Acupuncture therapy reduces blood pressure in hypertensive patients by stimulating acupoints located at specific anatomical positions with needles. Hydrogen sulfide (H 2 S) release and accumulation in the paraventricular nucleus (PVN) might be a pivotal step for triggering blood pressure reduction. But to date, the dynamics of H 2 S in the PVN during acupuncture treatment remain unclear. In this work, a multiple-nanomaterial-functionalized microneedle sensor is prepared for real-time monitoring of H 2 S in the PVN of rat while stimulated by electroacupuncture. Gold nanoparticles (AuNPs), molybdenum disulfide (MoS 2 ) and Ag 2 S were sequentially layered on the needle surface. The excellent electrical conductivity of AuNPs, the high carrier mobility of MoS 2 and the high catalytic performance of Ag 2 S ensure sensitive and specific detection of H 2 S in the range of 1 μM–100 μM with detection limit down to 95 nM. The microneedle sensor also demonstrates exceptional stability, remaining effective at room temperature for up to two weeks. Based on this, the microneedle sensor is used to monitor H 2 S release in vivo before and after acupuncture treatment. Our research indicates that acupuncture effectively increases H 2 S levels in the PVN of hypertensive rats, contributing to blood pressure reduction. This microneedle sensor provides a reliable method for monitoring H 2 S release in vivo, offering valuable insights into the role of H 2 S in the neurophysiology of hypertension and the mechanism of acupuncture in its treatment.
研究领域:
神经生理学
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生物传感技术
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中医药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BRITISH JOURNAL OF PHARMACOLOGY
·
2023
·
IF 7.3
Leilei Pan,Shuifeng Xiao,Zichao Xu,Wenping Li,Long Zhao,Ling Zhang,Ruirui Qi,Junqin Wang,Yiling Cai
Background and Purpose We evaluated the hypothesis that central orexin application could counteract motion sickness responses through regulating neural activity in target brain areas. Experimental Approach Thec effects of intracerebroventricular (i.c.v.) injection of orexin-A and SB-334867 (OX 1 antagonist) on motion sickness-induced anorexia, nausea-like behaviour (conditioned gaping), hypoactivity and hypothermia were investigated in rats subjected to Ferris wheel-like rotation. Orexin-A responsive brain areas were identified using Fos immunolabelling and were verified via motion sickness responses after intranucleus injection of orexin-A, SB-334867 and TCS-OX2-29 (OX 2 antagonist). The efficacy of intranasal application of orexin-A versus scopolamine on motion sickness symptoms in cats was also investigated. Key Results Orexin-A (i.c.v.) dose-dependently attenuated motion sickness-related behavioural responses and hypothermia. Fos expression was inhibited in the ventral part of the dorsomedial hypothalamus (DMV) and the paraventricular nucleus (PVN), but was enhanced in the ventral part of the premammillary nucleus ventral part (PMV) by orexin-A (20 μg) in rotated animals. Motion sickness responses were differentially inhibited by orexin-A injection into the DMV (anorexia and hypoactivity), the PVN (conditioned gaping) and the PMV (hypothermia). SB-334867 and TCS-OX2-29 (i.c.v. and intranucleus injection) inhibited behavioural and thermal effects of orexin-A. Orexin-A (60 μg·kg −1 ) and scopolamine inhibited rotation-induced emesis and non-retching/vomiting symptoms, while orexin-A also attenuated anorexia with mild salivation in motion sickness cats. Conclusion and Implications Orexin-A might relieve motion sickness through acting on OX 1 and OX 2 receptors in various hypothalamus nuclei. Intranasal orexin-A could be a potential strategy against motion sickness.
研究领域:
神经科学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
·
2016
·
IF 2.687
Zong-Lin Yang,Hui Li,Bing Wang,Shu-Ying Liu
Neurotransmitters (NTs) and their metabolites are known to play an essential role in maintaining various physiological functions in nervous system. However, there are many difficulties in the detection of NTs together with their metabolites in biological samples. A new method for NTs and their metabolites detection by high performance liquid chromatography coupled with Q Exactive hybrid quadruple-orbitrap high-resolution accurate mass spectrometry (HPLC–HRMS) was established in this paper. This method was a great development of the applying of Q Exactive MS in the quantitative analysis. This method enabled a rapid quantification of ten compounds within 18 min. Good linearity was obtained with a correlation coefficient above 0.99. The concentration range of the limit of detection (LOD) and the limit of quantitation (LOQ) level were 0.0008–0.05 nmol/mL and 0.002–25.0 nmol/mL respectively. Precisions (relative standard deviation, RSD) of this method were at 0.36–12.70%. Recovery ranges were between 81.83% and 118.04%. Concentrations of these compounds in mouse hypothalamus were detected by Q Exactive LC–MS technology with this method.
研究领域:
神经生物学
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分析化学
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医学
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产品关联
DOI
PubMed
高影响因子
IN VIVO
·
2024
·Vol. 38
·期 3
·1133-1142
·
IF 1.8
LONGJIE XU,LILI HOU,CHUN CAO,XIAOHUA LI
Background/Aim: Cancer-induced bone pain (CIBP) is one of the most common symptoms of bone metastasis of tumor cells. The hypothalamus may play a pivotal role in the regulation of CIBP. However, little is known about the exact mechanisms. Materials and Methods: First, we established a CIBP model to explore the relationship among hypothalamic ghrelin, NPY and CIBP. Then, we exogenously administered NPY and NPY receptor antagonists to investigate whether hypothalamic NPY exerted an antinociceptive effect through binding to NPY receptors. Finally, we exogenously administered ghrelin to investigate whether ghrelin alleviated CIBP by inducing the production of hypothalamic NPY through the AMPK-mTOR pathway. Body weight, food intake and behavioral indicators of CIBP were measured every 3 days. Hypothalamic ghrelin, NPY and the AMPK-mTOR pathway were also measured. Results: The expression of hypothalamic ghrelin and NPY was simultaneously decreased in cancer-bearing rats, which was accompanied by CIBP. Intracerebroventricular (i.c.v.) administration of NPY significantly alleviated CIBP in the short term. The antinociceptive effect of NPY was reversed with the i.c.v. administration of the Y1R and Y2R antagonists. The administration of ghrelin activated the AMPK-mTOR pathway and induced hypothalamic NPY production to alleviate CIBP. This effect of ghrelin on NPY and antinociception was reversed with the administration of a GHS-R1α antagonist. Conclusion: Ghrelin could induce the production of hypothalamic NPY through the AMPK-mTOR pathway to alleviate CIBP, which can provide a novel therapeutic mechanism for CIBP.
研究领域:
神经科学
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疼痛研究
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肿瘤学
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药理学
✓ 已验证
DOI
PubMed
高影响因子
Frontiers in Immunology
·
2022
·
IF 8.786
Chen Pan,Wu Hao,Yao Hongliang,Zhang Jiashuo,Fan Weiyang,Chen Zhen,Su Weiwei,Wang Yonggang,Li Peibo
Sleep disorders were associated with oral health. Inflammation has especially been thought to be a key factor in linking oral diseases and sleep deficiency. However, how chronic sleep deprivation (CSD) affects oral homeostasis, particularly oral inflammation and oral microbiota, is still unknown. This study aimed to uncover the systematic relationship between oral homeostasis and CSD in rats. The metabolomics in serum, proteomics in the tongue tissues, and microbiome analysis in the oral cavity in CSD rats were performed. Multi-omics data integration analysis was performed to uncover the systematic relationship between oral homeostasis and CSD through the weighted correlation network analysis. We found that CSD could lead to oral inflammation in rats. CSD significantly increased systemic inflammation by enhancing the serum levels of IL-1β, IL-6 and inhibiting the serum level of IL-10. Serum levels of adrenocorticotropin hormone, corticosterone, and triiodothyronine were increased in CSD rats, and the steroid hormone biosynthesis pathway was also found to be involved in the perturbation resulting from CSD, together suggesting the activation of the hypothalamic-pituitary-adrenocortical and hypothalamic‐pituitary‐thyroid axis. CSD led to changes of oral microbiota composition, and g_Acinetobacter, Candidatus Chryseobacterium massiliae, and g_Moraxella were significantly correlated with multiple proteins in bacterial invasion of epithelial cells pathway, which may partially responsible for oral inflammation resulting from CSD. The changes of proteomic profiling expression caused by CSD in tongue tissues were mainly enriched in neurodegenerative diseases pathways and immune/inflammation-related pathways. Multi-omics analysis indicated that the inflammatory response-related modules were significantly correlated with the neurodegenerative disease-related module suggesting a possible link between neurodegenerative diseases and oral inflammation. Together, CSD induced oral inflammation and subtle changes on oral microbiota. Our study is helpful to further understand the role that oral homeostasis plays in the process by which CSD affects human health and disease.
研究领域:
睡眠医学
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口腔健康
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免疫学
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微生物学
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系统生物学
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神经科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Environmental Research and Public Health
·
2017
·Vol. 14
·期 1
·44
·
IF 2.101
Xinwen Dong,Jin Dong,Yue Zhao,Jipeng Guo,Zhanju Wang,Mingqi Liu,Yunbo Zhang,Xiaolin Na
Di-(2-ethylhexyl)phthalate (DEHP) was a widely used chemical with human toxicity. Recent in vivo and in vitro studies suggested that DEHP-exposure may be associated with altered serum thyroid hormones (THs) levels, but the underlying molecular mechanisms were largely unknown. To explore the possible molecular mechanisms, 128 Wistar rats were dosed with DEHP by gavage at 0, 150, 300, and 600 mg/kg/day for 3 months (M) and 6 M, respectively. After exposure, expression of genes and proteins in the thyroid, pituitary, and hypothalamus tissues of rats were analyzed by Q-PCR and western blot, while the sera and urine samples were assayed by radioimmunoassay and ELISA. Results showed that serum THs levels were suppressed by DEHP on the whole. DEHP treatment influenced the levels of rats’ thyrotropin releasing hormone receptor (TRHr), Deiodinases 1 (D1), thyroid stimulating hormone beta (TSHβ), sodium iodide symporter (NIS), thyroid stimulating hormone receptor (TSHr), thyroperoxidase (TPO), thyroid transcription factor 1 (TTF-1), and thyroglobulin (TG) mRNA/protein expression in the hypothalamus-pituitary-thyroid (HPT) axis and decreased urine iodine. Taken together, observed findings indicate that DEHP could reduce thyroid hormones via disturbing the HPT axis, and the activated TSH/TSHR pathway is required to regulate thyroid function via altering TRHr, TSHβ, NIS, TSHr, TPO, TTF-1 and TG mRNA/protein expression of the HPT axis.Keywords:DEHP;hypothalamus-pituitary-thyroid axis;TSH/TSHR;signaling pathways;molecular mechanisms;thyroid function
研究领域:
毒理学
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内分泌学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
PLoS One
·
2016
·Vol. 11
·期 5
·e0155762
·
IF 3.057
Pan-Pan Jia,Yan-Bo Ma,Chun-Jiao Lu,Zakaria Mirza,Wei Zhang,Yong-Fang Jia,Wei-Guo Li,De-Sheng Pei
Di-(2-ethylhexyl) phthalate (DEHP) has the potential to disrupt the thyroid endocrine system, but the underlying mechanism is unknown. In this study, zebrafish ( Danio rerio ) embryos were exposed to different concentrations of DEHP (0, 40, 100, 200, 400 μg/L) from 2 to 168 hours post fertilization (hpf). Thyroid hormones (THs) levels and transcriptional profiling of key genes related to hypothalamus-pituitary-thyroid (HPT) axis were examined. The result of whole-body thyroxine (T4) and triiodothyronine (T3) indicated that the thyroid hormone homeostasis was disrupted by DEHP in the zebrafish larvae. After exposure to DEHP, the mRNA expressions of thyroid stimulating hormone ( tshβ ) and corticotrophin releasing hormone ( crh ) genes were increased in a concentration dependent manner, respectively. The expression level of genes involved in thyroid development ( nkx2 . 1 and pax8 ) and thyroid synthesis (sodium/iodide symporter, nis , thyroglobulin, tg ) were also measured. The transcripts of nkx2 . 1 and tg were significantly increased after DEHP exposure, while those of nis and pax8 had no significant change. Down-regulation of uridinediphosphate-glucuronosyl-transferase ( ugt1ab) and up-regulation of thyronine deiodinase ( dio2) might change the THs levels. In addition, the transcript of transthyretin ( ttr ) was up-regulated, while the mRNA levels of thyroid hormone receptors ( trα and trβ ) remained unchanged. All the results demonstrated that exposure to DEHP altered the whole-body thyroid hormones in the zebrafish larvae and changed the expression profiling of key genes related to HPT axis, proving that DEHP induced the thyroid endocrine toxicity and potentially affected the synthesis, regulation and action of thyroid hormones.
研究领域:
环境科学
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毒理学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NEURON
·
2022
·
IF 18.688
Yu-Ting Tseng,Binghao Zhao,Shanping Chen,Jialin Ye,Jingjing Liu,Lisha Liang,Hui Ding,Bernhard Schaefke,Qin Yang,Lina Wang,Feng Wang,Liping Wang
Summary When an animal faces a threatening situation while asleep, rapid arousal is the essential prerequisite for an adequate response. Here, we find that predator stimuli induce immediate arousal from REM sleep compared with NREM sleep. Using in vivo neural activity recording and cell-type-specific manipulations, we identify neurons in the medial subthalamic nucleus (mSTN) expressing corticotropin-releasing hormone (CRH) that mediate arousal and defensive responses to acute predator threats received through multiple sensory modalities across REM sleep and wakefulness. We observe involvement of the same neurons in the normal regulation of REM sleep and the adaptive increase in REM sleep induced by sustained predator stress. Projections to the lateral globus pallidus (LGP) are the effector pathway for the threat-coping responses and REM-sleep expression. Together, our findings suggest adaptive REM-sleep responses could be protective against threats and uncover a critical component of the neural circuitry at their basis.
研究领域:
神经科学
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睡眠研究
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行为神经科学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2023
·
IF 5.4
Xu Zhang,Xiaotong Wang,Rui Shi,Xiaoku Ran,Xiahong He,Deqiang Dou
Ethnopharmacological relevance Red ginseng (RG), a processed product of ginseng (GS), is a generally used qi -tonifying medicine in Traditional Chinese Medicine (TCM). According to the TCM principle, RG is also generally applied to spleen-deficiency syndrome (SDS) clinically for its warmer property. However, the effective substances and mechanism of RG on SDS have not been well investigated. Aim of the study The aim of this study was to explore the effective substances and their mechanism of RG on SDS. Materials and methods The SDS model was established with a compound factor method involving an irregular diet, excessive fatigue and sennae folium with a bitter-cold property. The medicine of RG was split by multi-mode separation methods and analyzed by ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS). The appearance indexes such as body weight, body temperature, swimming endurance, urine output, and water content of fecal were determined. The biochemical indexes such as D-xylose, SP , VIP and AChE in the digestive system, CRH, ACTH, CORT, E, T3, T4, T, E2 and 5-HT in the endocrine system, CS, NCR , IDH1 , COX and Na + -K + -ATPase in the metabolism of substance and energy, cAMP and cGMP in the cyclic nucleotide system were analyzed by Enzyme-linked immunosorbent assay (ELISA) kits and biochemical kits. The serum metabolites were analyzed by UPLC-QTOF/MS. Furthermore, the gut microbiota and short-chain fatty acids (SCFAs) in feces were analyzed by 16S rRNA sequencing and headspace gas chromatography-mass method. Results The pharmacological experiments showed that total saponin fraction (RGTSF), less polar fraction (RGLPF), and polysaccharides faction (RGPSF) significantly modulated the “brain-gut” axis-related indexes (the levels of VIP, AChE, and 5-HT). Besides, RGTSF also significantly modulated the hypothalamic-pituitary-adrenal (HPA) axis-related indexes as well as the substance and energy metabolism-related indexes (the levels of ACTH, CORT, A, Na + -K + -ATPase, COX, NCR and CS). RGPSF also significantly modulated the hypothalamus-pituitary-thyroid (HPT) axis-related indexes (the levels of T3 and T4). Secondly, metabolomics indicated that RGTSF could significantly regulate the abnormal metabolic pathways associated with the development of SDS, which involved steroid hormone biosynthesis, taurine and hypotaurine metabolism, primary bile acid biosynthesis, and amino acid metabolism. Subsequently, the study of gut microbiota indicated that RGLPF could increase the diversities of the gut microbiota and the relative abundance of Firmicutes in rats with SDS, while RGWEF significantly increased the relative abundance of Bacteroidetes . At the genus level, RGLPF could increase the relative abundance of Lactobacillus in rats with SDS and decrease that of Akkermansia . Meanwhile, the water-eluted fraction (RGWEF) showed a stronger regulation in SCFAs. Conclusion It is for the first time that the effective substances of red ginseng on spleen-deficiency syndrome were studied systematically, and the different mechanisms of the RG fractions involved in substance and energy metabolism as well as the “brain-gut” axis were revealed. The present study demonstrated that RGTSF, RGPSF, and RGLPF were the effective substances of red ginseng for ameliorating spleen-deficiency syndrome, indicating that ginsenosides composed of primary and secondary saponins as well as polysaccharides were the main effective substances for red ginseng in ameliorating spleen-deficiency syndrome.
研究领域:
民族药理学
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中医药学
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药理学
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代谢组学
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微生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR NEUROBIOLOGY
·
2022
·Vol. 59
·期 11
·6903-6917
·
IF 5.682
Zhao Maofang,Cheng Yuan,Wang Xiaoxuan,Cui Xiaoying,Cheng Xiaojing,Fu Qian,Song Yilin,Yu Peiquan,Liu Yi,Yu Yinghua
Obesity has become a public health epidemic worldwide and is associated with many diseases with high mortality including hypertension, diabetes, and heart disease. High-fat diet (HFD)-induced energy imbalance is one of the primary causes of obesity, but the underlying mechanisms are not fully elucidated. Our study showed that HFD reduced the level of hydrogen sulfide (H 2 S) and its catalytic enzyme cystathionine β-synthase (CBS) in mouse hypothalamus and plasma. We found that HFD activated mTOR, IKK/NF-κB, the main pathway regulating inflammation. Activation of inflammatory pathway promoted the production of pro-inflammatory cytokines including IL-6, IL-1β, and TNF-α, which caused cell damage and loss in the hypothalamus. The disturbance of the hypothalamic neuron circuits resulted in body weight gain in HFD-induced mice. Importantly, we also showed that restoration of H 2 S level with NaHS or activation of CBS with SAMe attenuated HFD-induced activation of mTOR, IKK/NF-κB signaling, which reduced the inflammation and the neuronal cell loss in the hypothalamus, and also inhibited body weight gain in mice. The same effects were obtained by inhibiting mTOR or NF-κB, which suggested that mTOR and NF-κB were the critical molecular factors involved in hypothalamic inflammation. Taken together, this study identified that HFD-induced hypothalamus inflammation plays a critical role in the development of obesity. Moreover, the inhibition of hypothalamic inflammation by regaining H 2 S level could be a potential therapeutic to prevent the development of obesity. Graphical abstract
研究领域:
营养学
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内分泌学
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免疫学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
CELL RESEARCH
·
2025
·
IF 25.9
Xie Ling-Qi,Hu Biao,Lu Ren-Bin,Cheng Ya-Lun,Chen Xin,Wen Jie,Xiao Yao,An Yu-Ze,Peng Ning,Dai Yu,Xie Genqing,Guo Qi,Peng Hui,Luo Xiang-Hang
Sleep deficiency is associated with obesity, but the mechanisms underlying this connection remain unclear. Here, we identify a sleep-inducible hypothalamic protein hormone in humans and mice that suppresses obesity. This hormone is cleaved from reticulocalbin-2 (RCN2), and we name it Raptin. Raptin release is timed by the circuit from vasopressin-expressing neurons in the suprachiasmatic nucleus to RCN2-positive neurons in the paraventricular nucleus. Raptin levels peak during sleep, which is blunted by sleep deficiency. Raptin binds to glutamate metabotropic receptor 3 (GRM3) in neurons of the hypothalamus and stomach to inhibit appetite and gastric emptying, respectively. Raptin-GRM3 signaling mediates anorexigenic effects via PI3K-AKT signaling. Of note, we verify the connections between deficiencies in the sleeping state, impaired Raptin release, and obesity in patients with sleep deficiency. Moreover, humans carrying an RCN2 nonsense variant present with night eating syndrome and obesity. These data define a unique hormone that suppresses food intake and prevents obesity.
研究领域:
神经科学
·
内分泌学
·
代谢研究
·
睡眠医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）