Journal of Environmental Chemical Engineering
·
2022
·
IF 7.968
Shinuo Wang,Yinghao Ruan,Ludong Yi,Di Liu,Jun Wang,Dawei Fang,Zhaohong Zhang
In this study, a thermally assisted hydrodynamic cavitation (HC) system was established by adding a water pre-heater in front of the cavitation device (orifice plate), which realizes the local heating of the flowing liquid, intensifies the HC effect and enhances Rhodamine B (RhB) degradation ratio and heat generation efficiency. The effects of preheating temperature, RhB initial concentration, orifice hole number, inlet pressure and solution volume on RhB HC degradation and heat generation were investigated. Free radical trapping experiments were performed to explore the active substances produced by the HC effect. Based on LC-MS and TOC data, the possible RhB degradation pathway and mechanism were proposed. When the preheating temperature rose from 10 °C to 50 °C, the RhB degradation ratio increased from 23.42% to 34.49% within 90 min cycle time, and the treatment cost decreased from 130.699 USD/m 3 to 91.701 USD/m 3 . At 30 min cycle time, the solution temperature rose from 45.6 °C to 56.4 °C, the heat production increased from 149.46 KJ/L to 194.81 KJ/L and the corresponding thermal efficiency increased from 47.45% to 61.84%. Further, at 60 min cycle time, under the conditions of 30 °C preheating temperature, 30 mg/L RhB initial concentration, 3-hole orifice plate, 3 bar inlet pressure and 5.0 L RhB solution volume, the RhB degradation ratio was the highest (40.38%). After Fenton reagent was used, the RhB degradation ratio and heat production both were further enhanced. At 60 min cycle time, the RhB degradation ratio was 65.52%, solution temperature rose to 72.8 °C, the heat production reached 131.83 KJ/L and the treatment cost was only 45.447 USD/m 3 at 30 °C preheating temperature. TOC test results show that the RhB mineralization ratio can reach 61.53% after 90 min cycle. All in all, this work proves that thermally assisted HC is an effective method to degrade organic dyes and generate heat, which can be used for large-scale treatment of organic dye wastewater.
研究领域:
环境科学
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化学工程
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DOI
高影响因子
Advanced Biology
·
2025
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IF 2.6
Shuai Wang,Ting He,Tong Fu,Yu Zhu,Yixin Wei,Wenlong Xie,Huanming Shen,Ya Luo,Boan Li,Huiling Guo,Weihua Li
Brown adipose tissue (BAT) is crucial for maintaining whole-body metabolic homeostasis and combating obesity and metabolic disorders. SOX4 collaborates with EBF2 to promote the expression of thermogenic genes in BAT, but it is unclear whether there are mechanisms independent of this regulation. However, it is found that SOX4 can directly interact with the promoter regions of thermogenic genes, thereby activating their expression. Simultaneously, early B cell factor 2 (EBF2) and peroxisome proliferator-activated receptor-γ (PPARγ) can independently interact with SOX4, forming two distinct complexes that promote the expression of thermogenic genes. Phenotypically, the deletion of SOX4 in BAT of mice ( Ucp1 Cre+ -Sox4 f/f ( Sox4-BKO )) leads to the downregulation of thermogenic and oxidative phosphorylation genes, as well as a reduction in mitochondrial numbers. Furthermore, Sox4-BKO mice are more susceptible to obesity, glucose intolerance, and insulin resistance when subjected to a high-fat diet (HFD). Consistently, the loss of SOX4 results in increased cellular triglyceride content and reduced expression levels of thermogenic genes in vitro. Together, a novel mechanism by which SOX4 regulates thermogenesis in BAT is elucidated, offering a promising strategy to address obesity and metabolic disorders.
研究领域:
分子生物学
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内分泌学
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代谢学
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脂肪生物学
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转录调控
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系统生物学
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产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2024
·
IF 6.7
Huijian Chen,Pengxin Liu,Ruitao Yu,Nabijan Mohammadtursun,Ainiwaer Aikemu,Xinzhou Yang
Background and purpose Swertiamarin (STM), a secoiridoid glycoside from Swertia chirayita (Roxb.) H. Karst , has been shown to decrease body weight, blood glucose, and blood lipids by inhibiting adipose tissue hypertrophy. However, the underlying mechanisms remain unclear. In particular, adipose thermogenesis is a novel avenue for exploring the pharmacological effects of STM. We aim to investigate the efficacy of STM on type 2 diabetes mellitus (T2DM), with a focus on underlying mechanisms, particularly the activation of ADRB3/UCP1 thermogenic signaling pathways. Methods T2DM model was established by a high-fat diet (HFD) and streptozotocin (STZ) in C57BL/6 J male mice. Mice were given to either 100 or 200 mg kg -1 /day of STM, or 200 mg kg -1 /day of metformin (Glucophage) via intragastric administration for 7 weeks. In vitro, 3T3-L1 cells were differentiated into adipocytes. Molecular markers related to ADRB3-UCP1 signals, lipolysis, and mitochondrial function were detected. Results STM-treated diabetic mice showed a reduction of body weight, fat mass, and blood glucose/lipids and an improvement in insulin sensitivity. Bioinformatics analysis indicated STM promoted lipid metabolism and mitochondrial function, features by closely associated with adipose thermogenesis. STM upregulated the lipolysis-related genes and p-HSL protein in inguinal subcutaneous white adipose tissue (igSWAT) and brown adipose tissue (BAT). STM-treated mice processed a more active energy metabolism. Additionally, the ADRB3-UCP1 signals, mitochondrial-related genes, and oxidative phosphorylation were improved in igSWAT and BAT. In vitro , we found STM interacted with ADRB3, increasing glucose uptake, glycerol release, ADRB3-UCP1 signals, p-HSL expression, mitochondrial content, oxidative phosphorylation complex expression with improved mitochondrial Δ ψ m, as well as reduced lipid accumulation in adipocytes. All these effects were reversed upon ADRB3 inhibition. Conclusion This study identifies a previously unknown role of STM activating ADRB3/UCP1 signals in adipose tissue, suggesting a potential strategy for treating T2DM.
研究领域:
药理学
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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
CELL DEATH AND DIFFERENTIATION
·
2024
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IF 13.7
Wang Shuai,He Ting,Luo Ya,Ren Kexin,Shen Huanming,Hou Lingfeng,Wei Yixin,Fu Tong,Xie Wenlong,Wang Peng,Hu Jie,Zhu Yu,Huang Zhengrong,Li Qiyuan,Li Weihua,Guo Huiling,Li Boan
Brown adipose tissue (BAT) is critical for non-shivering thermogenesis making it a promising therapeutic strategy to combat obesity and metabolic disease. However, the regulatory mechanisms underlying brown fat formation remain incompletely understood. Here, we found SOX4 is required for BAT development and thermogenic program. Depletion of SOX4 in BAT progenitors ( Sox4-MKO ) or brown adipocytes ( Sox4-BKO ) resulted in whitened BAT and hypothermia upon acute cold exposure. The reduced thermogenic capacity of Sox4-MKO mice increases their susceptibility to diet-induced obesity. Conversely, overexpression of SOX4 in BAT enhances thermogenesis counteracting diet-induced obesity. Mechanistically, SOX4 activates the transcription of EBF2, which determines brown fat fate. Moreover, phosphorylation of SOX4 at S235 by PKA facilitates its nuclear translocation and EBF2 transcription. Further, SOX4 cooperates with EBF2 to activate transcriptional programs governing thermogenic gene expression. These results demonstrate that SOX4 serves as an upstream regulator of EBF2, providing valuable insights into BAT development and thermogenic function maintenance.
研究领域:
分子生物学
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细胞生物学
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代谢
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肥胖研究
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产品关联
DOI
PubMed
高影响因子
Journal of Advanced Research
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2024
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IF 11.4
Sijia Lu,Quanxin Jiang,Peihui Zhou,Limin Yin,Ning Wang,Junting Xu,Qiqi Qian,Mijia Tao,Hanrui Yin,Liu Han,Yunqing Gu,Fei Gao,Junli Liu,Suzhen Chen
Introduction Promoting adipose thermogenesis is considered as a promising therapeutic intervention in obesity. However, endeavors to develop anti-obesity medications by targeting the canonical thermogenesis regulatory pathway, particularly β3-adrenergic receptor (β3-AR)-dependent mechanism, have failed due to the off-target effects of β3-AR agonists, exacerbating the risk of cardiovascular disease. Hyperforin (HPF), a natural compound extracted from the traditional herbal St. John’s Wort, binds to Dihydrolipoamide s-acetyltransferase (Dlat) and exerts effective anti-obesity properties through promoting adipose thermogenesis. Objectives The objective of this study was to investigate the oral efficacy and pharmacokinetics profile of HPF, and explore the detailed mechanism by which Dlat modulates HPF-mediated adipose thermogenesis. Methods To assess the anti-obesity efficacy of orally administered HPF in vivo , Dlat heterozygous knockout (Dlat +/- ) mice and wild-type (WT) mice, both fed a high-fat diet (HFD), underwent a validation process that involved the use of metabolic cages, NMR analysis, and infrared imaging. Sprague Dawley rats were employed to determine the pharmacokinetic parameters of HPF. Seahorse assays, JC-1 staining, qPCR, and immunoblotting were performed to evaluate cellular thermogenic efficacy of HPF and Dlat in vitro . Results Our study uncovered a non-canonical thermogenesis pathway involving Dlat, transient receptor potential vanilloid 3 (Trpv3, a calcium channel) and AMPK. Dlat interacted with Trpv3 to activate it, resulting in an increase in intracellular calcium (Ca 2+ ) and the activation of Camkkβ. Camkkβ then stimulated AMPK, leading to elevated Ucp1 expression and initiating adipose thermogenesis. HPF promoted thermogenesis in adipose tissues through enhancing the Dlat-Trpv3 interaction independently of β3-AR, causing minimal cardiac side effects. Notably, HPF’s thermogenic effects were reduced in Dlat +/- mice. Moreover, HPF exerted favorable oral bioavailability, a relatively long half-life, and extensive distribution within adipose tissues. Conclusion In summary, our study demonstrates that HPF targets a novel mechanism for promoting adipose thermogenesis and exhibits potent and safe anti-obesity efficacy.
研究领域:
药理学
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分子生物学
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代谢
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产品关联
DOI
PubMed
高影响因子
Food Bioscience
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2025
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IF 5.9
Zirou Yu,Chunjie Hou,Chenyu Shi,Ya Huang,Hu Liu,Fenglai Wang
Dietary fibers are classified into soluble and insoluble dietary fibers according to different solubility, which play different physiological roles. The study aimed to investigate the mechanism of dietary fiber solubility affecting thermogenesis and gut microbiota in rats. Twenty-four Sprague Dawley male rats were selected and divided randomly into 3 treatments. Dietary treatments included diet without dietary fiber (CON), control diet supplemented with 10 % inulin (SDF) and control diet supplemented with 10 % cellulose (IDF). The results showed that rats in the SDF group gained less body weight and had lower feed intake ( P < 0.001). The glucose tolerance of rats fed SDF and IDF was significantly improved ( P < 0.05). Compared with the CON group, the mRNA expression of thermogenesis-related genes CIDEA, HOXC8 and TMEM26 in inguinal white adipose tissue of rats in the SDF group and IDF group was significantly activated ( P < 0.05). The expression of brown adipose tissue thermogenesis-related proteins UCP1, CIDEA and HOXC8 in rats of SDF group was significantly increased ( P < 0.01). The abundance of Faecalibaculum and Gemmiger at the genus level, which both belonged to the order Clostridiales in the SDF group, was significantly increased ( P < 0.001). In conclusion, both SDF and IDF can regulate body thermogenesis by promoting browning of white adipose tissue. Particularly, SDF was able to further promote thermogenesis in rats by increasing the expression of UCP1 protein in brown adipose tissue and modulating the abundance of order Clostridium.
研究领域:
营养学
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分子生物学
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微生物学
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产品关联
DOI
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2024
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IF 6.2
Wenwen Zhu,Jiali Fang,Chenbo Ji,Hong Zhong,Tianying Zhong,Xianwei Cui
Background Neonicotinoids (NEOs) are well-designed highly selective pesticides that target nicotinic acetylcholine receptors. However, their extensive use, accumulation, and biomagnification pose significant risks to humans. Increasing evidence has suggested that NEOs may affect glucose homeostasis, but little research has linked NEOs exposure to gestational diabetes mellitus (GDM), which is the most common disease in pregnancy. We here aimed to investigate the association between NEOs exposure and GDM occurrence. Methods 100 pregnant women who completed a 75 g oral glucose tolerance test (OGTT) at 24–28 weeks of gestation were enrolled. Urinary concentrations of seven widely used NEOs were quantified using ultra-high performance liquid chromatography multiple reaction monitoring mass spectrometry (UHPLC-MRM-MS/MS). Correlation analysis revealed the associations between NEOs concentrations and glucose homeostasis parameters. The toxic effects of thiamethoxam (TMX) and clothianidin (CLO) were assessed using pregnant mice, and the potential mechanism in impairing glucose disposition regarding brown adipose tissue (BAT) thermogenesis has been elucidated. Results Among the 100 urine samples, 88 % were contaminated by NEOs with concentrations ranging from 2.50 to 491.34 nmol/L. TMX and CLO were the most frequently detected NEOs, highly detected in women with GDM. Moreover, we found statistically significant associations between TMX concentrations and 1hBG, and 2hBG. Exposure to mixed NEOs during gestation resulted in elevated glucose levels and impaired insulin sensitivity in normal pregnant and GDM mice models. In addition, we found the metabolic disorders induced by NEOs were linked to the deterioration of BAT thermogenesis in vivo . Conclusion In general, we demonstrated that prenatal exposures to NEOs were associated with an increased risk of GDM by deteriorating the thermogenic capacity of BAT
研究领域:
环境健康
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代谢
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毒理学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Nutrition
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2025
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IF 5.1
Ling Zhang,Zhou Peng,Caiyu Lin,Haixia Hu,Juan Du,Siqi Huang,Shan Huang,Jianfang Gao,Xirong Guo
Background: Traditional obesity interventions are often unsuitable for children. Breastfeeding has been shown to reduce obesity risk, potentially through bioactive metabolites in human milk. Here, we identified a human milk-derived metabolite, uridine 5′-monophosphate (5′-UMP), whose role in lipid metabolism and thermogenesis remains largely unknown.Methods: Untargeted metabolomics was performed on colostrum samples from obese and healthy mothers to identify obesity-associated metabolites. Zebrafish larvae and human preadipocytes were used to evaluate the anti-obesity effects of 5′-UMP. Lipid accumulation was assessed by Oil Red O and Nile Red staining, while mitochondrial function was analyzed using transgenic zebrafish [Tg(Xla. Eef1a1: mlsEGFP)] and fluorescent imaging.Results: Pyrimidine metabolism was significantly enriched in obese mothers, with orotate and 5′-UMP levels altered. Targeted analysis confirmed the presence of 5′-UMP in colostrum. Zebrafish toxicity assays confirmed 5′-UMP safety up to 200 μM. In the high-fat diet-induced zebrafish obesity model, 5′-UMP treatment significantly reduced abdominal lipid accumulation. In adipocytes, 5′-UMP enhanced mitochondrial respiration and increased mRNA and protein expression of PGC1-α and UCP1. Furthermore, mitochondrial fluorescence intensity and protein levels of NRF1 and MFN2 were elevated, indicating enhanced mitochondrial biogenesis and activity.Conclusion: Maternal obesity is associated with changes in the human milk metabolome. 5′-UMP, a nucleotide metabolite enriched in human milk, promotes thermogenesis and mitochondrial activation, effectively ameliorating obesity in zebrafish and human adipocytes. These findings support its potential as a safe, milk-derived therapeutic candidate for pediatric obesity intervention.
研究领域:
营养学
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代谢生物学
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分子生物学
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儿科学
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转化医学
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内分泌学
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产品关联
DOI
PubMed
高影响因子
EMBO REPORTS
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2021
·Vol. 22
·期 3
·e50629
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IF 8.807
Lei Liu,Yanjun Li,Jianing Wang,Di Zhang,Hao Wu,Wenhui Li,Huifang Wei,Na Ta,Yuyuan Fan,Yujiao Liu,Xiaohui Wang,Jun Wang,Xin Pan,Xudong Liao,Yushan Zhu,Quan Chen
Mitophagy is an essential cellular autophagic process that selectively removes superfluous and damaged mitochondria, and it is coordinated with mitochondrial biogenesis to fine tune the quantity and quality of mitochondria. Coordination between these two opposing processes to maintain the functional mitochondrial network is of paramount importance for normal cellular and organismal metabolism. However, the underlying mechanism is not completely understood. Here we report that PGC-1α and nuclear respiratory factor 1 (NRF1), master regulators of mitochondrial biogenesis and metabolic adaptation, also transcriptionally upregulate the gene encoding FUNDC1, a previously characterized mitophagy receptor, in response to cold stress in brown fat tissue. NRF1 binds to the classic consensus site in the promoter of Fundc1 to upregulate its expression and to enhance mitophagy through its interaction with LC3. Specific knockout of Fundc1 in BAT results in reduced mitochondrial turnover and accumulation of functionally compromised mitochondria, leading to impaired adaptive thermogenesis. Our results demonstrate that FUNDC1-dependent mitophagy is directly coupled with mitochondrial biogenesis through the PGC-1α/NRF1 pathway, which dictates mitochondrial quantity, quality, and turnover and contributes to adaptive thermogenesis.
研究领域:
细胞生物学
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分子生物学
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代谢
✓ 已验证
DOI
PubMed
高影响因子
PHYTOMEDICINE
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2024
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IF 6.7
Fukui Shen,Wen Yang,Guoqing Luan,Jiamin Peng,Zhenqiang Li,Jie Gao,Yuanyuan Hou,Gang Bai
Background Catalpol (CAT), a naturally occurring iridoid glycoside sourced from the root of Rehmannia glutinosa , affects mitochondrial metabolic functions. However, the mechanism of action of CAT against pyrexia and its plausible targets remain to be fully elucidated. Purpose This study aimed to identify the specific targets of CAT for blocking mitochondrial thermogenesis and to unveil the unique biological mechanism of action of the orthogonal binding mode between the hemiacetal group and lysine residue on the target protein in vivo . Methods Lipopolysaccharide (LPS)/ carbonyl cyanide 3-chlorophenylhydrazone (CCCP)-induced fever models were established to evaluate the potential antipyretic effects of CAT. An alkenyl-modified CAT probe was designed to identify and capture potential targets. Binding capacity was tested using in-gel imaging and a cellular thermal shift assay. The underlying antipyretic mechanisms were explored using biochemical and molecular biological methods. Catalpolaglycone (CA) was coupled with protein profile identification and molecular docking analysis to evaluate and identify its binding mode to UCP2. Results After deglycation of CAT in vivo , the hemiacetal group in CA covalently binds to Lys239 of UCP2 in the mitochondria of the liver via an ɛ-amine nucleophilic addition. This irreversible binding affects proton leakage and improves mitochondrial membrane potential and ADP/ATP transformation efficiency, leading to an antipyretic effect. Conclusion Our findings highlight the potential role of CA in modulating UCP2 activity or function within the mitochondria and open new avenues for investigating the therapeutic effects of CA on mitochondrial homeostasis.
研究领域:
药理学
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分子生物学
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生物化学
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DOI
PubMed
高影响因子
Journal of Biomedical Research
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2022
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IF 0
Mo-qiu Jia,Yong-jin Wang,Kang Fu,Han Jiao,Jia Sun,Yuanqing Gao
Orexin signaling has been associated with energy expenditure and brown adipose tissue (BAT) function. However, conflicting data exist in the field about how orexin signaling regulates BAT thermogenesis. In this study, we show that a specific orexin receptor type 2 (OX2R) agonist [Ala11, D-Leu15]-OxB (OB-Ala) inhibited intrascapular brown adipose tissue (iBAT) thermogenesis by reducing sympathetic output to iBAT. This effect is mediated by OX2Rs located on afferent nerve endings innervating iBAT instead of brown adipocyte itself. Microinjection of OB-Ala into iBAT inhibited iBAT thermogenesis in mice upon cold exposure and neuronal activity in the paraventricular nucleus. Findings suggest that OB-Ala could inhibit iBAT thermogenesis by attenuating sensory input thereby inhibiting the sympathetic-sensory iBAT feedback loop. Our study uncovers a novel primary action site of orexin in the regulation of energy balance.
研究领域:
神经科学
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内分泌学
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代谢
✓ 已验证
产品关联
DOI
PubMed
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
·
2023
·Vol. 325
·期 4
·E376
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IF 5.1
Meijuan Dong,Kun An,Li Mao
Download figureDownload PowerPointHyperuricemia (HUA) is strongly associated with the increasing prevalence of obesity, but the underlying mechanism remains elusive. Dysfunction of brown adipose tissue (BAT) could lead to obesity. However, studies on the role of HUA on BAT are lacking. Our retrospective clinical analysis showed that serum uric acid (UA) is significantly associated with BAT in humans. To investigate the role of UA in regulating BAT function, we used UA to treat primary brown adipocytes (BACs) in vitro and established HUA mice. In vitro results showed that HUA suppressed thermogenic gene expression and oxygen consumption rate. Accordingly, HUA mice exhibited lower energy expenditure and body temperature, with larger lipid droplets and lower thermogenic gene expression. These results demonstrate that HUA inhibits BAT thermogenic capacity in vitro and in vivo. To further elucidate the mechanism of UA on adipocytes, mRNA-sequencing analysis was performed and screened for “AMP-activated protein kinase (AMPK) signaling pathway” and “mitochondrial biogenesis.” Further tests in vivo and in vitro showed that the phosphorylation of AMPK was suppressed by HUA. Activation of AMPK alleviated the inhibition of AMPK phosphorylation by HUA and increased mitochondrial biogenesis, subsequently restoring the impaired BAT thermogenic capacity in vitro and vivo. Thus, we confirmed that HUA suppresses mitochondrial biogenesis by regulating AMPK, thereby inhibiting BAT thermogenic capacity. Taken together, our study identifies UA as a novel regulator of BAT thermogenic capacity, providing a new strategy to combat obesity.NEW & NOTEWORTHY To investigate the effect and mechanism of UA on BAT thermogenic capacity, we established HUA models in vitro and in vivo, and performed RNA sequencing analysis. Our results revealed that HUA suppresses mitochondrial biogenesis by regulating AMPK, thereby inhibiting BAT thermogenic capacity. Taken together, our study identifies UA as a novel regulator of BAT thermogenic capacity, providing a new strategy to combat obesity.
研究领域:
内分泌学
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代谢学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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