Frontiers in Neuroscience
·
2023
·
IF 4.3
Xue Tao,Wang Shu,Chen Shujun,Wang Huizhi,Liu Chong,Shi Lin,Bai Yutong,Zhang Chunkui,Han Chunlei,Zhang Jianguo
Background: Focal motor seizures that originate in the motor region are a considerable challenge because of the high risk of permanent motor deficits after resection. Deep brain stimulation of the subthalamic nucleus (STN-DBS) is a potential treatment for motor epilepsy that may enhance the antiepileptic actions of the substantia nigra pars reticulata (SNr). Orexin and its receptors have a relationship with both STN-DBS and epilepsy. We aimed to investigate whether and how STN inputs to the SNr regulate seizures and the role of the orexin pathway in this process.Methods: A penicillin-induced motor epileptic model in adult male C57BL/6 J mice was established to evaluate the efficacy of STN-DBS in modulating seizure activities. Optogenetic and chemogenetic approaches were employed to regulate STN-SNr circuits. Selective orexin receptor type 1 and 2 antagonists were used to inhibit the orexin pathway.Results: First, we found that high-frequency ipsilateral or bilateral STN-DBS was effective in reducing seizure activity in the penicillin-induced motor epilepsy model. Second, inhibition of STN excitatory neurons and STN-SNr projections alleviates seizure activities, whereas their activation amplifies seizure activities. In addition, activation of the STN-SNr circuits also reversed the protective effect of STN-DBS on motor epilepsy. Finally, we observed that STN-DBS reduced the elevated expression of orexin and its receptors in the SNr during seizures and that using a combination of selective orexin receptor antagonists also reduced seizure activity.Conclusion: STN-DBS helps reduce motor seizure activity by inhibiting the STN-SNr circuit. Additionally, orexin receptor antagonists show potential in suppressing motor seizure activity and may be a promising therapeutic option in the future.
研究领域:
神经科学
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医学
·
药理学
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DOI
PubMed
高影响因子
Food & Function
·
2020
·Vol. 11
·期 9
·7596-7610
·
IF 4.171
Longchen Shang,Yi Wang,Yanyan Ren,Tingyang Ai,Peiyuan Zhou,Ling Hu,Ling Wang,Jing Li,Bin Li
Konjac glucomannan (KGM) is associated with the satiety-enhancing property by imparting the food matrix with high viscosity. In the present study, rheology tests on KGM sol with different viscosities were conducted to understand its flow behavior as they presented in the mouth and stomach, and the in vitro gastric emptying characteristics of KGM were examined with a human gastric simulator. Then, their effects on subjective appetite, glycemia, and appetite-related hormones (insulin, GLP-1, PYY3-36, CCK-8, ghrelin) response were investigated by conducting a randomized, single-blind, crossover trial in 22 healthy adults (11 female and 11 male, mean age (years): 23.2 ± 2.0, BMI (kg m−2): 20.6 ± 2.1). The blood samples and ratings for subjective appetite were collected at regular time intervals after the subjects were fed with four test breakfasts (one control treatment and three experimental treatments) on four different days. An ad libitum lunch was provided to the subjects once they consumed the breakfasts and their food intake was recorded. As the viscosity increased, the gastric emptying rate was delayed despite a large part of the chyme viscosity lost during digestion. The satiating capacity of the test breakfast was significantly enhanced as its viscosity increased, the and subjects’ sensation for hunger, fullness, desire-to-eat, and prospective food consumption differed significantly (p = 0.006, 0.000, 0.002, and 0.001, respectively) between the treatments. The secretion of glycemia and satiety-related hormones were beneficially modulated by the increased viscosity of the test meal but a small decrease in the ad libitum food intake was observed after the intervention of the viscous test breakfasts. Overall, elevating the meal viscosity moderately by using KGM could contribute to combating the challenge of hunger for people in the bodyweight management.
研究领域:
营养学
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食品科学
·
生理学
✓ 已验证
DOI
高影响因子
Heliyon
·
2024
·
IF 3.4
Hongyan Li,Yanzhi Zeng,Guangjun Wang,Kai Zhang,Wangbao Gong,Zhifei Li,Jingjing Tian,Yun Xia,Wenping Xie,Jun Xie,Shouqi Xie,Ermeng Yu
Diets with high carbohydrate (HC) was reported to have influence on appetite and intermediary metabolism in fish. To illustrate whether betaine could improve appetite and glucose-lipid metabolism in aquatic animals, mandarin fish ( Siniperca chuatsi ) were fed with the HC diets with or without betaine for 8 weeks. The results suggested that betaine enhanced feed intake by regulating the hypothalamic appetite genes. The HC diet-induced downregulation of AMPK and appetite genes was also positively correlated with the decreased autophagy genes, suggesting a possible mechanism that AMPK/mTOR signaling might regulate appetite through autophagy. The HC diet remarkably elevated transcriptional levels of genes related to lipogenesis, while betaine alleviated the HC-induced hepatic lipid deposition. Additionally, betaine supplementation tended to store the energy storage as hepatic glycogen. Our findings proposed the possible mechanism for appetite regulation through autophagy via AMPK/mTOR, and demonstrated the feasibility of betaine as an aquafeed additive to regulate appetite and intermediary metabolism in fish.
研究领域:
水产养殖学
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营养学
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分子生物学
✓ 已验证
产品关联
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
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内分泌学
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代谢研究
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睡眠医学
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产品关联
DOI
PubMed
高影响因子
MOLECULES
·
2024
·Vol. 29
·期 7
·1681
·
IF 4.2
Chenfeng Xu,Kaixuan Cheng,Yu Kang,Chao Cheng,Chi Zhang,Longchen Shang
The physical characteristics of chyme during gastrointestinal digestion are considered to significantly affect nutrient digestion and absorption (such as glucose diffusion), which has an impact on postprandial satiety. The present study aims to analyze the hydration rate (HR) and rheological properties of deacetylated konjac glucomannan (DKGM) at different degrees and then explore their effects on rice texture, digestive properties, and the subjects’ post-meal appetite. The present results show that, as the deacetylation degree (DD) of KGM increased, the intersection point of the viscoelastic modulus shifted to a high shear rate frequency, and as the swelling time of the DKGM was prolonged, its HR decreased significantly. The results of the in vitro gastrointestinal digestion tests show that the hardness and chewability of the rice in the fast-hydration group (MK1) were remarkably reduced. In contrast, the slow-hydration group (MK5) exhibited an outstanding ability to resist digestion. The kinetics of starch hydrolysis revealed that the HR of the rice in the fast-hydration group was 1.8 times faster than that of the slow-hydration group. Moreover, it was found that the subjects’ appetite after the meal was highly related to the HR of the MK. Their hunger (p< 0.001), desire to eat (p< 0.001), and prospective food consumption (p< 0.001) were significantly inhibited in the slow-hydration group (MK5) compared to the control. This study explored the nutritional effects of the hydration properties derived from the DKGM, which may contribute to modifying the high glycemic index food and provide ideas for the fabrication of food with enhanced satiating capacity.
研究领域:
营养科学
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食品科学
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胃肠生理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2025
·
IF 6.1
Xuejun Yuan,Wenjie Chen,Rui Li,Huijun Guo,Chunyang Wang
Deoxynivalenol (DON) is one of the most prevalent mycotoxins and can induce weight loss and vomiting in animals. This study aimed to elucidate the molecular mechanisms underlying DON-induced anorexia in rabbits through the microbial-gut-brain axis. A total of forty rabbits were randomly divided into a DON group and a control group, receiving 1.5 mg/kg.BW of DON and an equivalent volume of saline daily via intragastric administration, respectively. The pre-treatment period lasted for 7 days, followed by a formal experimental period of 24 days. The findings revealed that DON exposure significantly reduced daily food intake and weight gain, leading to intestinal apoptosis and barrier injuries. 16S rRNA sequencing data indicated that DON exposure decreased the diversity and richness of cecal microflora, suppressed probiotic populations, and disrupted host lipid metabolism. RNA-Seq and iTRAQ data were used to cross-analyze the shared differentially expressed genes (DEGs) and differentially expressed proteins (DEPs) in the hypothalamus and jejunum, along with their shared enrichment pathways, indicating that TNF-α, NF-κB, and NPY may play pivotal roles in DON-induced anorexia. qRT-PCR and Western blotting results confirmed significant increases in mRNA and protein expression levels of TNF-α, NF-κB and 5-HT2A in both the hypothalamus and jejunum. In conclusion, DON ingestion in rabbits can disrupt the intestinal barrier, up-regulate the expression of IFN-γ, TNF-α, NF-κB, and 5-HT2A in the intestine, and trigger an immuno-inflammatory response in the hypothalamus via the microbial-gut-brain axis, ultimately resulting in appetite suppression and weight loss.
研究领域:
毒理学
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分子生物学
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微生物学
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动物科学
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营养学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Zhejiang University-SCIENCE B
·
2024
·
IF 4.7
Jia Xiaodan,Lu Ke,Liang Xufang
Neuropeptide Y receptor Y8 (NPY8R) is a fish-specific receptor with two subtypes, NPY8AR and NPY8BR. Changes in expression levels during physiological processes or in vivo regulation after ventricular injection suggest that NPY8BR plays an important role in feeding regulation; this has been found in only a few fish, at present. In order to better understand the physiological function of npy8br , especially in digestion, we used clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) technology to generate npy8br −/− Japanese medaka ( Oryzias latipes ). We found that the deletion of npy8br in medaka larvae affected their feeding and digestion ability, ultimately affecting their growth. Specifically, npy8br deficiency in medaka larvae resulted in decreased feed intake and decreased expression levels of orexigenic genes ( npy and agrp ). npy8br −/− medaka larvae fed for 10 d (10th day of feeding) still had incompletely digested brine shrimp ( Artemia nauplii ) in the digestive tract 8 h after feeding, the messenger RNA (mRNA) expression levels of digestion-related genes ( amy, lpl, ctra , and ctrb ) were significantly decreased, and the activity of amylase, trypsin, and lipase also significantly decreased. The deletion of npy8br in medaka larvae inhibited the growth and significantly decreased the expression of growth-related genes ( gh and igf1 ). Hematoxylin and eosin (H&E) sections of intestinal tissue showed that npy8br −/− medaka larvae had damaged intestine, thinned intestinal wall, and shortened intestinal villi. So far, this is the first npy8br gene knockout model established in fish and the first demonstration that npy8br plays an important role in digestion.
研究领域:
分子生物学
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遗传学
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水产养殖
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生理学
✓ 已验证
DOI
PubMed
高影响因子
Food & Function
·
2024
·
IF 5.1
Sijia Zhu,Jiyu Yang,Pengkui Xia,Sha Li,Qi Wang,Kaikai Li,Bin Li,Jing Li
Konjac glucomannan (KGM) is a dietary fiber supplement that exhibits multiple biological activities, including weight control and regulation of glucose and lipid metabolism. Currently, KGM intake patterns in practical applications include KGM sol, thermal irreversible gel, and frozen thermal irreversible gel. In this study, four intake patterns of KGM, namely KGM sol (KS), deacetylated KGM (DK), KGM gel (KG) and frozen KGM gel (FKG), were used as materials to explore the effects of KGM intake patterns on glucose and lipid metabolism and intestinal flora of obese mice induced by high fat diet under the same dose. Results showed that any type of KGM intake could reduce body weight, fat mass, lipid levels, and insulin resistance in obese mice, as well as partially alleviating liver damage and inflammation caused by obesity. However, KS has the most significant effect on controlling blood glucose and blood lipid in obese mice. Additionally, it was found that KS, DK, KG and FKG can increase the α-diversity of intestinal microflora in high-fat mice, and improve the microflora disorder in high-fat mice. Finally, KS may increase the levels of fasting appetite hormones GLP-1 and PYY in mice, up-regulate the expression of LDLR, GCK and G-6-pase mRNA, and increase the production of short-chain fatty acids (SCFAs) in the intestinal flora of mice, thus regulating glucose and lipid metabolism . This study systematically investigated the effects of different intake forms of KGM on metabolism and intestinal flora in obese mice, which is of great significance for further understanding the role of KGM in the prevention and treatment of obesity metabolic diseases, and for developing targeted dietary interventions.
研究领域:
营养学
·
代谢研究
·
肥胖研究
·
肠道微生物
✓ 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）