Journal of Functional Foods
·
2020
·
IF 3.701
Xing Zhang,Wen Shi,Hui He,Ruge Cao,Tao Hou
Val-Phe-Val-Arg-Asn (VFVRN) has been identified and screened from lipid-lowering chickpea peptides (ChPs) previously. This work explored its lipid-lowering mechanisms by using a high-fat diet C57BL/6J mice model and 3T3-L1 preadipocyte cell model. Administration of VFVRN to hyperlipidemic mice significantly decreased the levels of total cholesterol (TC) and total triglyceride (TG) in liver and serum (P < 0.05), and increased the fecal triglyceride excretions. The expressions of sterol regulatory element-binding protein (SREBP)-2, liver X receptor (LXR)α, peroxisome proliferator-activated receptors (PPAR)α and their related target genes were regulated via AMP-activated protein kinase (p-AMPK) pathway in liver. Compared with model group, the levels of PPARα and PPARγ in 10 mg/kg VFVRN group were up-regulated by 36.96% and 36.49% in adipose tissues, while LXRα and ATP binding cassette G5/8 transporters (ABGC5/8) were lowered by 87.26% and 145% in small intestine respectively. Moreover, VFVRN promoted 3T3-L1 preadipocyte apoptosis by regulating the expressions of BaX, Caspase-3 and Bcl-2.
研究领域:
营养学
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分子生物学
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药理学
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产品关联
DOI
高影响因子
RSC Advances
·
2019
·Vol. 9
·期 2
·924-930
·
IF 3.049
Fei Zeng,Zengju Fan,Shanshan Wu,Xing Cheng,Yanqing Tian
A new type of biocompatible and photo-polymerizable hydrogel with oxygen sensors for microengineering was developed. Herein, a red emitter as an oxygen probe which was chemically immobilized in a poly(2-hydroxyethyl methacrylate)-co-polyacrylamide-based matrix was expected to monitor cell metabolism. A few micropatterned films with gratings (5, 7, 10, 20, and 50 μm in width, respectively and with 1.2 μm in height) were designed and fabricated by photo-lithography using these hydrogels. SEM and AFM were used to validate these films to attain their lateral width and vertical depth. The oxygen responses of these films were characterized. Results showed that patterned films exhibited higher sensitivity than the non-patterned films. The films' construction can also have some influence on cell alignment and elongation. This phenomenon was evaluated by culturing human cervical cancer cells (HeLa cells) and mouse embryo fibroblasts (3T3-L1), on the film surfaces with different construction. Linear correlation between cell elongation and the logarithm of grating width was observed. Real-time monitoring of oxygen consumption of HeLa cells in cell culture medium was achieved. This study is expected to have potential to be applied in micro-structured design and to help understanding metabolism.
研究领域:
生物工程
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细胞生物学
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材料科学
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产品关联
DOI
PubMed
高影响因子
ACS Omega
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2020
·
IF 2.87
Dong-Dong Li,Pan Yu,Zhen-Zhong Wang,Wei Xiao,Xin-Hu Zhou,Lin-Guo Zhao
Berberine (BBR), a well-known alkaloid, exhibits various pharmacological activities, especially hypolipidemic activity, which has attracted much interest from medicinal chemists in the past decade. However, little progress was made on the structural modification of BBR for improving lipid-lowering activity, mainly due to its unclear biological target and low safety. In this study, a new scaffold of 7,9-disulfatetrahydroberberine was discovered unexpectedly, provided with extremely low cytotoxicity. Hence, a novel series of highly safe 7,9-disulfatetrahydroberberines were designed, synthesized, and evaluated for their hypolipidemic activities. In order to investigate the significance of the 9-position substituent, another new series of 7-sulfatetrahydroberberines were designed and synthesized. Lipid-lowering experiments showed that among these compounds, 5f exhibited the best lipid-lowering activity based on two cell models, 3T3-L1 cells and HepG2 cells. Compared with the blank control, the inhibition rate of compound 5f against total cholesterol was over 60%, the inhibition rate against triglyceride was over 70%, the inhibition rate against low-density lipoprotein cholesterol was approximately 75%, and the inhibition rate against high-density lipoprotein cholesterol was close to 50%, which were far superior to the positive control BBR. This result also verified the feasibility of the development of BBR as a lipid-lowering drug via disubstituted modification at the 7- and 9-position.
研究领域:
药物化学
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药理学
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DOI
PubMed
高影响因子
Chinese Journal of Natural Medicines
·
2016
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IF 1.382
Feng TIAN,Hao-Yu LV,Ji-Long ZOU,Yi WANG,Meng-Jun DUAN,Xiao-Qin CHU,Dan LI,Liang ZHU,Jian-Qin JIANG
The present study was designed to synthesize and evaluate a series of benzylisoquinoline derivatives. These compounds were synthesized by Bischler-Napieralski cyclization to yield 1-benzyl-3,4-dihydroisoquinolines, and the products were obtained by reductions. All these compounds were identified by MS, 1 H NMR and 13 C NMR. The inhibitory activities on pancreatic lipase and preadipocyte proliferation for the synthesized compounds and alkaloids from Nulembo nucifera were assessed in vitro . Most of the compounds showed inhibitory activities on both pancreatic lipase and preadipocyte proliferation. Particularly, compounds 7p–7u and 9d–9f exhibited significant inhibitory activity on pancreatic lipase while compounds 7c, 7d, 7f, 7g, 7i , and 7j potently inhibited the proliferation of 3T3-L1 preadipocytes. Our results provided a basis for future evaluation and development of these compounds as leads for therapeutics for human diseases.
研究领域:
药理学
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有机合成化学
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代谢性疾病研究
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DOI
PubMed
高影响因子
LWT-FOOD SCIENCE AND TECHNOLOGY
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2023
·
IF 6
Fangliang Li,Tongjie Luo,Jiale Hou,Tao Fei,Jiachao Zhang,Lu Wang
Raspberry leaf as a tea substitute has been consumed in China for long time. In this work, the inhibitory activities of raspberry leaf-tea (RLT) extract on α -glucosidase ( α -GLU)/ α -amylase ( α -AMY) were measured, and the effects of the RLT extract on the glucose consumption of 3T-3L1 cells were also investigated. Results confirmed that RLT 70% ethanol extract (REE) exhibited strong inhibitory activities on α -GLU/ α -AMY in vitro . In addition, REE remarkably improved the glucose consumption of 3T-3L1 cells. Subsequently, eight major inhibitors including epigallocatechin gallate (EGCG), delphinidin-3- O -glucoside, cyanidin-3-rutinoside, isoorientin, procyanidin C3, dihydromyricetin, rutin, and isovitexin were screened and identified through affinity ultrafiltration combined with HPLC-MS/MS. Confirmation tests verified that these major compounds were responsible the inhibitory activities of the REE on α -GLU/ α -AMY. Molecular docking studies revealed that these inhibitors can well interact with α -GLU/ α -AMY via van der Waals force or hydrogen bonding, thus inhibiting their activities. In a short, raspberry leaf can be exploited as a promising anti-hypoglycemic material. This study provides a theoretical basis for discovering active components from medicinal plants using affinity ultra-filtration with multi-targets.
研究领域:
食品科学
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植物化学
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分子生物学
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产品关联
DOI
高影响因子
LIPIDS
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2020
·Vol. 55
·期 3
·251-260
·
IF 1.919
Bingnan He,Xia Wang,Xini Jin,Zimeng Xue,Yinhua Ni,Jianbo Zhu,Caiyun Wang,Yuanxiang Jin,Zhengwei Fu
Studies have elucidated that pyrethroids induce adipogenesis. It is also known that macrophages can affect the homeostasis of adipose tissue. However, whether and how the β-cypermethrin (β-CYP)-mediated inhibition of the macrophages affects adipogenesis remain unknown. To explore the effects of β-CYP on adipogenesis through modulating the function of macrophages, 3T3-L1 cells, a preadipocyte cell line, were exposed to culture medium from either RAW 264.7 cells, a macrophage cell line (RM), or β-CYP-treated RAW 264.7 cells (CRM). CRM decreased the inhibitory effects of RM treatment on cell proliferation and adipogenesis, as lipid accumulation, the CEBPA content, and Fasn and Acaca expression in 3T3-L1 cells were higher following CRM treatment than following RM treatment through the higher levels of the demethylated CEBPA promoter in 3T3-L1 cells. However, the medium from β-CYP- and N-acetyl-L-cysteine-cotreated RAW 264.7 cells (CNRM) partially restored the inhibitory effects of RAW 264.7 cells on 3T3-L1 cells that had been reduced by CRM, indicating that β-CYP might reduce the cytotoxicity and inhibitory effects of RAW 264.7 cells on the adipogenesis of 3T3-L1 cells through elevating ROS levels in RAW 264.7 cells. Moreover, exposure to β-CYP downregulated the TNF-α secretion in RAW 264.7 cells. In conclusion, these data demonstrated that β-CYP affected the function of RAW 264.7 cells, alleviating their inhibitory effects on adipogenesis and CEBPA demethylation in 3T3-L1 cells. β-CYP might achieve these effects through downregulating the secretion of TNF-α via elevating ROS levels in RAW 264.7 cells. Our experiments provide a new perspective on the obesogenic effect of pyrethroids.
研究领域:
毒理学
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细胞生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2021
·
IF 5.279
Jing Zhou,Ji Zhang,Jiayi Li,Yiqiu Guan,Ting Shen,Fu Li,Xueqin Li,Xiaojun Yang,Weicheng Hu
Ginsenoside F2 (GF2) is a protopanaxdiol saponin from Panax ginseng leaves and possesses many potential pharmacological properties. GF2 may prevent obesity by directly binding to the peroxisome proliferator-activated receptor-γ (PPARγ) and inhibiting adipocyte differentiation. However, the mechanism by which GF2 alleviates obesity is unknown. We therefore explored the anti-adipogenesis and anti-obesity effects of GF2 in vitro and in vivo. GF2 inhibited differentiation and reduced the triglyceride (TG) content of 3T3-L1 preadipocytes in the early stage of adipogenesis. Administration of GF2 (50 and 100 mg/kg) to obese mice for 4 weeks reduced the body weight gain, weight of adipose tissues, adipocyte size, and total cholesterol, TG, and AST levels in serum. RNA sequencing and real-time quantitative PCR indicated that GF2 decreased the expression levels of adipokines, including PPARγ, fatty acid synthase, and adiponectin. KEGG enrichment and western blot analyses demonstrated that GF2 accelerated the phosphorylation of AMPK and ACC in vitro and in vivo. Moreover, GF2 promoted the biosynthesis of mitochondria in 3T3-L1 adipocytes and increased the expression of antioxidant enzymes such as SOD and GSH-Px in the liver of obese mice. Therefore, GF2 suppressed adipogenesis and obesity by regulating the expression of adipokines and activating the AMPK pathway. Hence, the findings suggest that GF2 may have potential therapeutic implications to treat obesity.
研究领域:
药理学
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分子生物学
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细胞生物学
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代谢
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2023
·
IF 6.1
Bowen Qin,Yijun Yao,Jing Zhang,Lifeng Wang
At present, most of the research on coix seed polyphenols (CSPs) focuses on the separation, purification, structure analysis, and biological functions of specific components, and few studies have considered the overall bioavailability and the metabolites that play a role after digestion and absorption and their biological functional activities. In this study, we constructed a MKN28 and Caco-2 cell monolayer continuous transport model (MCTM) to study the bioavailability of CSPs in the digestion and absorption stages of the stomach and small intestine. Using this model, we innovatively divided CSPs into easy-to-digest and hard-to-digest polyphenols and studied their intracellular lipid-lowering function and their influence on human intestinal flora. Transwell experiments showed that ferulic acid, rutin, naringin, arbutin, and syringetin had high transmembrane transport efficiency, especially syringetin. The methylation reaction in the monolayer membrane of Caco-2 cells may be the reason for the higher transport rate of syringetin. Further experiments showed that CPL reduced TG accumulation by more than 50% during 3T3-L1 differentiation and promoted the transformation of adipocytes into brown cells (p < 0.05). Finally, in vitro fermentation experiments showed that CSP_AP can increase the abundance of Lactobacillus and Bifidobacterium of human gut microbiota at the genus level (p < 0.05).
研究领域:
药理学
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营养学
·
细胞生物学
·
胃肠生理学
·
微生物学
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产品关联
DOI
PubMed
高影响因子
MOLECULAR AND CELLULAR ENDOCRINOLOGY
·
2020
·
IF 3.871
Ziwen Wei,Xiaoli Qin,Xiaojie Kang,Haixia Zhou,Shaodan Wang,Dong Wei
Background MiR-142-3p has been shown to be suppressed in obese patients , while the underlying regulatory mechanism is unclear. Methods Body shape indexes as well as peripheral blood for biochemical parameter analysis were obtained from obese and healthy subjects. When 3T3-L1 cells were induced to differentiate, miR-142-3p expression was detected by quantitative real-time polymerase chain reaction (qRT-PCR). The effects of miR-142-3p on triglyceride (TG) and adipogenic differentiation-related genes during the adipogenic differentiation of 3T3-L1 cells were detected by transfection, Oil Red O staining, and Western blot . The targeting relationship between miR-142-3p and Krueppel-like transcription factor 9 (KLF9) was verified by TargetScan and dual-luciferase experiment. The specific regulatory effects of miR-142-3p on cell adipogenic differentiation and autophagy were analyzed by rescue experiments. In vivo experiments further validated the results of in vitro experiments through obese mouse models. Results Obesity-marked biochemical indicators increased whereas high density lipoprotein and miR-142-3p decreased in obese patients. The content of miR-142-3p gradually decreased with cell lipid differentiation. Overexpression of miR-142-3p reduced TG deposition in cells by down-regulating lipid formation and fatty acid synthesis genes and up-regulating fatty acid oxidation genes. KLF9 targeting miR-142-3p was suppressed by miR-142-3p. KLF9 overexpression partially reversed the inhibitory effect of miR-142-3p mimic on adipogenic differentiation and the expressions of autophagy related-genes in 3T3-L1 cells. MiR-142-3p overexpression also inhibited fat cell differentiation and autophagy in obese mice . Conclusion Overexpressed miR-142-3p inhibited adipogenic differentiation and autophagy through targeting KLF9.
研究领域:
分子生物学
·
细胞生物学
·
内分泌学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF NUTRITIONAL BIOCHEMISTRY
·
2022
·
IF 6.117
Lingli Zhao,Mengfei Zheng,Hao Cai,Juan Chen,Yan Lin,Fangbin Wang,Lu Wang,Xian Zhang,Jian Liu
Mitochondrial reactive oxygen species (ROS)generation plays an essential role in the process of adipocyte differentiation and is involved in the development of obesity and associated metabolic diseases . Various dietary flavonoids possess the substantial anti-adipogenic activity. However, it is unclear whether these flavonoids inhibit adipocyte differentiation by reducing ROS generation. In this study, the effects of six common dietary flavonoids on adipocyte differentiation were assessed in 3T3-L1 cells. The flavonoids with the same backbone of 5,7-dihydroxylflavone, including flavones apigenin , chrysin , luteolin and flavonols kaempferol , myricetin , quercetin , dose-dependently inhibited 3T3-L1 adipocyte differentiation, suggesting an associated hierarchy of inhibitory capability: luteolin > quercetin > myricetin > apigenin/kaempferol > chrysin. Meanwhile, six flavonoids were found to inhibit adipogenic gene expression and the early stage of adipocyte differentiation. Among the tested flavonoids, luteolin significantly reduced both intracellular and mitochondrial ROS generation during adipocyte differentiation. Further, luteolin treatment depressed the elevation of H 2 O 2 concentration in the early stage of 3T3-L1 differentiation and reversed the facilitated effects of exogenous H 2 O 2 on 3T3-L1 adipocyte differentiation and ROS generation. Altogether, the activity comparison of six dietary flavonoids identifies that luteolin inhibits 3T3-L1 adipocyte differentiation through reducing ROS generation, elucidating a new mechanism underlying the anti-adipogenic actions of flavonoids.
研究领域:
药理学
·
细胞生物学
·
营养学
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产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2024
·
IF 2.5
Yao Jiang,Wei Wang,Hui Wang,Xiaoru Zhang,Yuling Kong,Yong Q. Chen,Shenglong Zhu
Aberrant adipogenic differentiation is strongly associated with obesity and related metabolic diseases. Elucidating the key factors driving adipogenesis is an effective strategy for identifying novel therapeutic targets for treating metabolic diseases represented by obesity. In this study, transcriptomic techniques were employed to investigate the functional genes that regulate adipogenic differentiation in OP9 cells and 3T3-L1 cells. The findings indicated a notable upregulation of Acsl1 expression throughout the adipogenic differentiation process. Knocking down Acsl1 led to a decrease in the expression of genes associated with adipogenesis and a reduction in triglyceride accumulation. Additionally, Acsl1 overexpression promoted adipocyte differentiation and adipose-specific overexpression of Acsl1 markedly aggravated steatosis induced by a high-fat diet. Mechanistically, Cyp2f2, Dusp23 and Gstm2 are the crucial genes implicated in Acsl1-induced adipogenic differentiation. The findings of this study indicate that Acsl1 promotes adipogenesis and could serve as a potential therapeutic target for treating obesity and related metabolic disorders.
研究领域:
分子生物学
·
细胞生物学
·
代谢
·
肥胖研究
✓ 已验证
DOI
高影响因子
MOLECULAR AND CELLULAR ENDOCRINOLOGY
·
2019
·
IF 3.693
Wen Qi,Liting Zhou,Tianye Zhao,Shuang Ding,Qi Xu,Xu Han,Yaming Zhao,Xinyue Song,Tianyang Zhao,Xiaohan Zhang,Lin Ye
Background Mono-2-ethylhexyl phthalate (MEHP), an important metabolite of di (2-ethylhexyl) phthalate (DEHP), can induce lipid metabolic disorder . Previous studies have shown that MEHP promotes 3T3-L1 cell differentiation ; however, the underlying mechanism is unclear. The present study was performed to investigate the effect of the TYK-2/STAT-3 pathway on lipid accumulation induced by MEHP. Methods A 3T3-L1 precursor adipocyte differentiation model was exposed to MEHP. 3-Isobutyl-1-methylxanthine (IBMX), dexamethasone (DEX), and insulin were used to establish the 3T3-L1 precursor adipocyte differentiation model. Then the model cells were exposed to MEHP for 8 d. The lipid droplet formation in 3T3-L1 cells was determined with Oil-Red-O staining, and isopropyl alcohol was used to extract the lipid droplets for quantification. Flow cytometry was used to detect the intracellular reactive oxygen species (ROS) and mitochondrial membrane potential . Quantitative real-time polymerase chain reaction (qPCR) was used to detect mRNA expression, and western blotting was used to detect the expression of proteins encoded by TYK-2/STAT-3 pathway genes and adipogenesis-related genes. Results MEHP treatment , compared with the control treatment, significantly promoted the differentiation of 3T3-L1 cells and increased the expression of STAT-3 mRNA and protein and P-STAT3 protein in the cells. In addition, MEHP down-regulated the phosphorylation of STAT-3 in mitochondria. MEHP was found to influence the mitochondrial membrane potential and intracellular ROS levels. Conclusion MEHP may affect adipocyte differentiation and lead to lipid accumulation through the TYK-2/STAT-3 pathway.
研究领域:
毒理学
·
细胞生物学
·
分子生物学
✓ 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）