Nature Communications
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2024
·Vol. 15
·期 1
·1-18
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IF 14.7
Qiu Sheng,Wu Qinan,Wang Hao,Liu Dongfang,Chen Chen,Zhu Zhiming,Zheng Hongting,Yang Gangyi,Li Ling,Yang Mengliu
Zinc-alpha2-glycoprotein (AZGP1) has been implicated in peripheral metabolism; however, its role in regulating energy metabolism in the brain, particularly in POMC neurons, remains unknown. Here, we show that AZGP1 in POMC neurons plays a crucial role in controlling whole-body metabolism. POMC neuron-specific overexpression of Azgp1 under high-fat diet conditions reduces energy intake, raises energy expenditure, elevates peripheral tissue leptin and insulin sensitivity, alleviates liver steatosis, and promotes adipose tissue browning. Conversely, mice with inducible deletion of Azgp1 in POMC neurons exhibit the opposite metabolic phenotypes, showing increased susceptibility to diet-induced obesity. Notably, an increase in AZGP1 signaling in the hypothalamus elevates STAT3 phosphorylation and increases POMC neuron excitability. Mechanistically, AZGP1 enhances leptin-JAK2-STAT3 signaling by interacting with acylglycerol kinase (AGK) to block its ubiquitination degradation. Collectively, these results suggest that AZGP1 plays a crucial role in regulating energy homeostasis and glucose/lipid metabolism by acting on hypothalamic POMC neurons.
研究领域:
神经科学
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代谢研究
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分子生物学
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内分泌学
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Scientific Reports
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2026
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IF 4.9
Zhu Anming,Liu Junxi,Liu Youyun,Xu Rui,Yuan Yonglei,Sun Qiwen,Wang Feifei,Qu Liping
Metapanax delavayi (Franch.) J. Wen & Frodin (Araliaceae) is a plant with both medicinal and edible value, but there is no study examining its effects on skin neurogenic inflammation. We investigated the anti-neurogenic inflammatory and soothing potential of Metapanax delavayi extract (MDE) in vitro using SH-SY5Y cells activated by capsaicin and HaCaT cells stimulated by substance P, and in vivo using a heat-induced zebrafish model. We found that MDE significantly inhibited TRPV1 activation and intracellular calcium influx, down-regulated neuropeptides (CGRP, NGF, substance P) and proinflammatory cytokines (IL-1α, IL-6, IL-8), and regulated emotion-related hormones (decreased cortisol, increased β-endorphin). It also reduced heat-induced hypermotility in zebrafish. Critically, the mechanistic study suggests that biological activity may be associated with the inactivation of the CRHR1/POMC/MC1R signaling pathway. Collectively, these findings indicate that MDE possesses significant potential as a natural skincare ingredient for counteracting neurogenic inflammation associated with sensitive skin.
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高影响因子
Water
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2024
·Vol. 16
·期 23
·3478
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IF 3
Menglan Su,Rongkai Bao,Bo Gao,Xiaobin Liao,Peng Xiao,Wenhua Li
Diafenthiuron is a novel derivative of thiourea and is highly toxic to non-target organisms, necessitating its efficient removal from wastewater before discharge. This study compared diafenthiuron removal efficiencies at a target concentration of 1 µM using three methods: a 4 mg/L ozone (O3) treatment; an ultraviolet (UV) light treatment, applying UV254radiation with a fluence of 60 mJ/cm2for 10 min; and a combined O3/UV treatment utilizing ozone and ultraviolet light. An acute toxicity assessment was conducted using a modeled zebrafish embryo (Danio rerio). The diafenthiuron removal efficiencies were 49.59%, 54.51%, and 68.90% for the UV light, O3, and O3/UV treatments, respectively. The treatments showed additional benefits of exerting no negative impacts on the survival rate, heart rate, or body length of the zebrafish larvae posttreatment. The survival and heart rates at 120 hpf, as well as the body length at 96 and 120 hpf, showed significant differences between the advanced oxidation and 1 μM diafenthiuron treatment groups. However, these parameters remained consistent with those of the control group. The three treatments alleviated the spatiotemporal downregulation of the liver-specific markerfabp10acaused by diafenthiuron exposure. The UV light and O3/UV treatments were efficient at degrading diafenthiuron, causing decreased reactive oxygen species levels and increasedpomcandprlexpression levels. The O3-treated diafenthiuron and 1 μM diafenthiuron treatments increased the reactive oxygen species levels and decreased thepomcandprlexpression levels. The combined O3/UV treatment showed the highest removal efficiency and the least toxicity, making it the most effective method for diafenthiuron degradation. This study provides valuable insights into the treatment of diafenthiuron-laden wastewater.
研究领域:
环境科学
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毒理学
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水生生物学
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Nature Communications
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2024
·Vol. 15
·期 1
·1-17
·
IF 14.7
Jiang Xiaoxue,liu Kan,Luo Peixiang,Li Zi,Xiao Fei,Jiang Haizhou,Wu Shangming,Tang Min,Yuan Feixiang,Li Xiaoying,Shu Yousheng,Peng Bo,Chen Shanghai,Ni Shihong,Guo Feifan
The central nervous system has been implicated in the age-induced reduction in adipose tissue lipolysis. However, the underlying mechanisms remain unclear. Here, we show the expression of SLC7A14 is reduced in proopiomelanocortin (POMC) neurons of aged mice. Overexpression of SLC7A14 in POMC neurons alleviates the aging-reduced lipolysis, whereas SLC7A14 deletion mimics the age-induced lipolysis impairment. Metabolomics analysis reveals that POMC SLC7A14 increased taurochenodeoxycholic acid (TCDCA) content, which mediates the SLC7A14 knockout- or age-induced WAT lipolysis impairment. Furthermore, SLC7A14-increased TCDCA content is dependent on intestinal apical sodium-dependent bile acid transporter (ASBT), which is regulated by intestinal sympathetic afferent nerves. Finally, SLC7A14 regulates the intestinal sympathetic afferent nerves by inhibiting mTORC1 signaling through inhibiting TSC1 phosphorylation. Collectively, our study suggests the function for central SLC7A14 and an upstream mechanism for the mTORC1 signaling pathway. Moreover, our data provides insights into the brain–gut–adipose tissue crosstalk in age-induced lipolysis impairment.
研究领域:
神经科学
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内分泌学
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代谢学
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衰老研究
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PubMed
高影响因子
Frontiers in Cellular and Infection Microbiology
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2021
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IF 5.293
Yinrui Guo,Hongya Guo,Lingyan Qiu,Yuanfei Fu,Xiangxiang Zhu,Haiting Zhang,Jian Wang,Diling Chen
It is known that the microbiome affects human physiology, emotion, disease, growth, and development. Most humans exhibit reduced appetites under high temperature and high humidity (HTHH) conditions, and HTHH environments favor fungal growth. Therefore, we hypothesized that the colonic mycobiota may affect the host’s appetite under HTHH conditions. Changes in humidity are also associated with autoimmune diseases. In the current study mice were fed in an HTHH environment (32°C ± 2°C, relative humidity 95%) maintained via an artificial climate box for 8 hours per day for 21 days. Food intake, the colonic fungal microbiome, the feces metabolome, and appetite regulators were monitored. Components of the interleukin 17 pathway were also examined. In the experimental groups food intake and body weight were reduced, and the colonic mycobiota and fecal metabolome were substantially altered compared to control groups maintained at 25°C ± 2°C and relative humidity 65%. The appetite-related proteins LEPT and POMC were upregulated in the hypothalamus ( p < 0.05), and NYP gene expression was downregulated ( p < 0.05). The expression levels of PYY and O-linked β-N-acetylglucosamine were altered in colonic tissues ( p < 0.05), and interleukin 17 expression was upregulated in the colon. There was a strong correlation between colonic fungus and sugar metabolism. In fimo some metabolites of cholesterol, tromethamine, and cadaverine were significantly increased. There was significant elevation of the characteristic fungi Solicoccozyma aeria , and associated appetite suppression and interleukin 17 receptor signaling activation in some susceptible hosts, and disturbance of gut bacteria and fungi. The results indicate that the gut mycobiota plays an important role in the hypothalamus endocrine system with respect to appetite regulation via the gut-brain axis, and also plays an indispensable role in the stability of the gut microbiome and immunity. The mechanisms involved in these associations require extensive further studies.
研究领域:
微生物学
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免疫学
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神经科学
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分子生物学
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生理学
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PSYCHOPHARMACOLOGY
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2024
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IF 3.5
Liu Xin,Jin Yongzeng,Cheng Xinyi,Song Qinghua,Wang Yanan,He Ling,Chen Tong
Rationale The plasma ceramide levels in Alzheimer’s disease (AD) patients are found abnormally elevated, which is related to cognitive decline. Objectives This research was aimed to investigate the mechanisms of aberrant elevated ceramides in the pathogenesis of AD. Results The ICR mice intracerebroventricularly injected with Aβ 1-42 and APP/PS1 transgenic mice were employed as AD mice. The cognitive deficiency, impaired episodic and spatial memory were observed without altered spontaneous ability. The serum levels of p-tau and ceramide were evidently elevated. The modified expressions and activities of glycogen synthase kinase-3β (GSK-3β) and protein phosphatase 2A (PP2A) influenced the serum content of p-tau. The levels of ceramide synthesis-related genes including sptlc1, sptlc2, cers2, and cers6 in the liver of AD mice were increased, while the ceramide degradation-related gene asah2 did not significantly change. The regulations of these genes were conducted by activated nuclear factor kappa-B (NF-κB) signaling. NF-κB, promoted by free fatty acid (FFA), also increased the hepatic concentrations of proinflammatory cytokines. The FFA amount was modulated by fatty acid synthesis-related genes acc1 and srebp-1c. Besides, the decreased levels of pre-proopiomelanocortin (pomc) mRNA and increased agouti-related protein (agrp) mRNA were found in the hypothalamus without significant alteration of melanocortin receptor 4 (MC4R) mRNA. The bioinformatic analyses proved the results using GEO datasets and AlzData. Conclusions Ceramide was positively related to the increased p-tau and impaired cognitive function. The increased generation of ceramide and endoplasmic reticulum stress in the hypothalamus was positively related to fatty acid synthesis and NF-κB signaling via brain–liver axis.
研究领域:
神经科学
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药理学
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分子生物学
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病理学
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PubMed
高影响因子
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