FOOD RESEARCH INTERNATIONAL
·
2025
·
IF 8
Linlin He,Lan Zhang,Fanyi Meng,Jingge Wei,Fei Chen,Siqi Qin,Ge Jin,Hailong Cao
Intestinal senescence, often characterized by increased oxidative stress, is linked to gastrointestinal disorders such as inflammatory bowel disease and colorectal cancer. While previous studies have suggested that diets rich in food additives, such as the emulsifier Polysorbate 80 (P80), may influence gut health, the impact of P80 exposure on intestinal senescence remains unclear. This study aimed to explore the effects of P80 on intestinal senescence in a senescence-accelerated mouse prone model. The results revealed that P80 exposure could damage the intestinal barrier, induce oxidative stress, and accelerate intestinal senescence. Mechanistically, P80 activated the peroxisome proliferator-activated receptor-α (PPARα) and fatty acid-binding protein 1 (FABP1) axis, increasing intestinal fatty acid absorption and triggering lipotoxicity, which promoted senescence. Additionally, P80 exacerbated D-galactose-induced epithelial cell senescence and lipid accumulation via the PPARα signalling pathway. Importantly, the PPARα antagonist GW6471 mitigated fatty acid uptake and reduced senescence in the intestine. In conclusion, the emulsifier P80 accelerated intestinal senescence by regulating the PPARα-FABP1 axis to induce intestinal fatty acid uptake and lipotoxicity, suggesting new insights into the adverse effects of food additives on gut health.
研究领域:
营养学
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分子生物学
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胃肠病学
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产品关联
DOI
PubMed
高影响因子
BRITISH JOURNAL OF PHARMACOLOGY
·
2025
·
IF 7.7
Wenxian Chen,Tongzhu Jin,Yilin Xie,Changsheng Zhong,Huiying Gao,Lei Zhang,Jin Ju,Ting Cheng,Mengyang Li,Huifang Wang,Zhenbo Yang,Qin Deng,Zhimin Du,Haihai Liang
Background and Purpose Emerging evidence indicated that the excessive lipid droplets (LDs) accumulation and lipotoxicity play a significant role in the development of diabetic cardiomyopathy (DCM), yet the regulatory mechanisms governing the function of cardiac LDs are still unknown. Lipophagy has been shown to be involved in the maintenance of LDs homeostasis. The objective of this study was to explore the mechanism of lipophagy in cardiomyocytes and investigate whether berberine could mitigate DCM by modulating this pathway. Experimental Approach Bioinformatics analysis identified disorders of lipid metabolism and autophagy in DCM. To carry out further research, db/db mice were utilized. Furthermore, H9C2 cells treated with palmitic acid were employed as a model to explore the molecular mechanisms involved in myocardial lipotoxicity. Key Results The results showed that lipophagy was impaired in DCM. Mechanistically, sirtuin 3 (SIRT3) was demonstrated to regulate lipophagy in cardiomyocytes. SIRT3 was down-regulated in DCM. Conversely, activation of SIRT3 by the activator nicotinamide riboside (NR) could promote lipophagy to alleviate PA-induced lipotoxicity in H9C2 cells. Moreover, berberine administration markedly mitigated diabetes-induced cardiac dysfunction and hypertrophy in db/db mice, which dependent on SIRT3-mediated lipophagy. Conclusion and Implications Collectively, SIRT3 could moderate cardiac lipotoxicity in DCM by promoting lipophagy, suggesting that the regulation of SIRT3-mediated lipophagy may be a promising strategy for treating DCM. The findings indicate that the therapeutic potential of berberine for DCM is associated with lipophagy.
研究领域:
心血管医学
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代谢生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2022
·
IF 5.988
Xue Tian,Xu Chen,Qianqian Jiang,Qianbin Sun,Tiantian Liu,Yiqin Hong,Yawen Zhang,Yanyan Jiang,Mingyan Shao,Ran Yang,Chun Li,Qiyan Wang,Yong Wang
Aims: Cardiac lipotoxicity is the common consequence of lipid metabolism disorders in cardiomyocytes during development of heart failure (HF). Adenosine 5′monophosphate-activated protein kinase (AMPK) acts as an energy sensor and has a beneficial effect in reducing lipotoxicity. Notoginsenoside R1 (NGR1) is extracted from the traditional Chinese medicine Panax notoginseng (Burkill) F.H.Chen (P. notoginseng) and has definite cardioprotective effects. However, whether NGR1 can attenuate HF by mitigating lipotoxicity has not been elucidated yet. This study aimed to explore whether NGR1 plays a protective role against HF by ameliorating cardiac lipotoxicity via the AMPK pathway.
Methods: In this study, HF mice model was established by left anterior descending (LAD) ligation. palmitic acid (PA) stimulated H9C2 cell model was applied to clarify the effects and potential mechanism of NGR1 on lipotoxicity. In vivo, NGR1 (7.14 mg/kg/days) and positive drug (simvastatin: 2.9 mg/kg/days) were orally administered for 14 days. Echocardiography was applied to assess heart functions. Lipid levels were measured by Enzyme-linked immunosorbent assay (ELISA) and key proteins in the AMPK pathway were detected by western blots. In vitro, NGR1 (40 μmol/L) or Compound C (an inhibitor of AMPK, 10 μmol/L) was co-cultured with PA stimulation for 24 h in H9C2 cells. CCK-8 assay was used to detect cell viability. Key lipotoxicity-related proteins were detected by western blots and the LipidTOX™ neutral lipid stains were used to assess lipid accumulation. In addition, Apoptosis was assessed by Hoechst/PI staining.
Results: NGR1 could significantly improve the cardiac function and myocardial injury in mice with HF and up-regulate the expression of p-AMPK. Impressively, NGR1 inhibited the synthesis of diacylglycerol (DAG) and ceramide and promoted fatty acid oxidation (FAO) in vivo. Moreover, NGR1 significantly promoted expression of CPT-1A, the key enzyme in FAO pathway, and down-regulated the expression of GPAT and SPT, which were the key enzymes catalyzing production of DAG and ceramide. In vitro experiments showed that NGR1 could significantly attenuate lipid accumulation in PA-induced H9C2 cells and the Hoechst/PI staining results showed that NGR1 ameliorated lipotoxicity-induced apoptosis in PA-stimulated H9C2 cell model. Furthermore, co-treatment with inhibitor of AMPK abrogated the protective effects of NGR1. The regulative effects of NGR1 on lipid metabolism were also reversed by AMPK inhibitor.
Conclusion: NGR1 could significantly improve the heart function of mice with HF and reduce cardiac lipotoxicity. The cardio-protective effects of NGR1 are mediated by the activation of AMPK pathway.Keywords: heart failure, cardiac lipotoxicity, NGR1, AMPK, apoptosis
研究领域:
心脏病学
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药理学
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分子生物学
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DOI
PubMed
高影响因子
Nanomaterials
·
2022
·Vol. 12
·期 4
·672
·
IF 5.719
Pengxiang Zhao,Yi Jin,Xiang Wu,Jin Huang,Lupeng Chen,Yanjie Tan,Hong Yuan,Jian Wu,Zhuqing Ren
Lipid droplets (LDs) play an important role in the regulation of cellular stress. This suggests LDs can be applied as safe and effective biomaterials to alleviate cellular stress and lipotoxicity. Here, we constructed a convenient method to generate stable and pure artificial lipid droplets (aLDs). aLDs can maintain their biological function by incubating LD-associated proteins or organelles in vitro. It was validated that perilipin-coated aLDs could be uptaken by cells, significantly reducing hydrogen peroxide-induced reactive oxidative species (ROS) and alleviating cellular lipotoxicity caused by excess fatty acid. Our work demonstrated a direct role of LDs in regulating cellular stress levels, providing methods and potential value for future research and medical applications of LDs.Keywords:artificial lipid droplets;biomaterials;lipotoxicity;ROS;Plin5;cell stress
研究领域:
细胞生物学
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生物医学工程
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药学
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产品关联
DOI
PubMed
高影响因子
Food Bioscience
·
2023
·
IF 5.2
Hengju Ge,Jiaxin Li,Yang Xu,Jiahong Xie,Naymul Karim,Fujie Yan,Jianling Mo,Wei Chen
Fructus Gardeniae (FG) is the dried ripe fruit of Gardenia jasminoides Ellis, having beneficial effects for human health. In this study, we discovered that the most relevant pathway influenced by Fructus Gardeniae extract (FGE) is lipid metabolism according to the analysis of network pharmacology. Furthermore, the protective effect of FGE against palmitic acid-induced lipotoxicity was investigated. In L02 cells, FGE significantly promoted cellular proliferation after being treated with palmitic acid , and reduced the accumulation of lipid droplets and triglyceride level . Palmitic acid led to an increase of ROS content, which was reduced by FGE. Additionally, FGE could facilitate Nrf2 localized to nuclear and followed by activating its downstream targets. ML385 (a Nrf2 inhibitor) treatment further proved that FGE attenuated lipotoxicity through regulating Nrf2/ARE pathway. Consequently, we demonstrated for the first time FGE could be regarded as potential functional food materials for hepatic protection.
研究领域:
药理学
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肝脏病学
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产品关联
DOI
高影响因子
Reproductive Biology and Endocrinology
·
2018
·Vol. 16
·期 1
·1-11
·
IF 2.852
Ge Xie,Pan Peng,Jing Jun,Hu Xuechun,Chen Li,Qiu Xuhua,Ma Rujun,Jueraitetibaike Kadiliya,Huang Xuan,Yao Bing
The Sertoli cell is the only somatic cell within the seminiferous tubules, and is vital for testis development and spermatogenesis. Rosiglitazone (RSG) is a member of the thiazolidinedione family and is a peroxisome proliferator-activated receptor-γ (PPARγ) agonist. It has been reported that RSG protects various types of cells from fatty acid-induced damage. However, whether RSG serves a protective role in Sertoli cells against palmitic acid (PA)-induced toxicity remains to be elucidated. Therefore, the aim of the present study was to investigate the effect of RSG on PA-induced cytotoxicity in Sertoli cells. MTT assay and Oil Red O staining revealed that RSG ameliorated the PA-induced decrease in TM4 cell viability, which was accompanied by an alleviation of PA-induced lipid accumulation in cells. In primary mouse Sertoli cells, RSG also showed similar protective effects against PA-induced lipotoxicity. Knockdown of PPARγ verified that RSG exerted its protective role in TM4 cells through a PPARγ-dependent pathway. To evaluate the mechanism underlying the protective role of RSG on PA-induced lipotoxicity, the present study analyzed the effects of RSG on PA uptake, and the expression of genes associated with both fatty acid oxidation and triglyceride synthesis. The results demonstrated that although RSG did not affect the endocytosis of PA, it significantly elevated the expression of carnitine palmitoyltransferase (CPT)-1A, a key enzyme involved in fatty acid oxidation, which indicated that the protective effect of RSG may have an important role in fatty acid oxidation. On the other hand, the expression of CPT1B was not affected by RSG. Moreover, the expression levels of diacylglycerol O-acyltransferase (DGAT)-1 and DGAT2, both of which encode enzymes catalyzing the synthesis of triglycerides, were not suppressed by RSG. The results indicated that RSG reduced PA-induced lipid accumulation by promoting fatty acid oxidation mediated by CPT1A. The effect of RSG in protecting cells from lipotoxicity was also found to be specific to Sertoli cells and hepatocytes, and not to other cell types that do not store excess lipid in large quantities, such as human umbilical vein endothelial cells. These findings provide insights into the cytoprotective effects of RSG on Sertoli cells and suggest that PPARγ activation may be a useful therapeutic method for the treatment of Sertoli cell dysfunction caused by dyslipidemia.
研究领域:
药理学
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细胞生物学
·
内分泌学
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DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2019
·
IF 3.571
Dongwen Hu,Tao Bao,Yang Lu,Hongming Su,Huihui Ke,Wei Chen
This study was aimed to investigate the protective effects of three different mulberry fruit polysaccharide fractions (MFP-I, MFP-II, and MFP-III) against palmitic acid (PA)-induced hepatocyte lipotoxicity and characterize the functional polysaccharide fraction using gel permeation chromatography, high-performance liquid chromatography, Fourier transform infrared spectroscopy, and nuclear magnetic resonance analyses. MFP-I, MFP-II, and MFP-III were isolated from mulberry fruit by stepwise precipitation with 30, 60, and 90% ethanol, respectively. MFP-II at 0.1 and 0.2 mg/mL dramatically attenuated PA-induced hepatic lipotoxicity, while MFP-I and MFP-III showed weak protection. It was demonstrated that MFP-II not only increased nuclear factor erythroid-2-related factor 2 (Nrf2) phosphorylation and its nuclear translocation, thereby activating the Nrf2/ARE signaling pathway, but also enhanced heme oxygenase 1, NAD(P)H:quinone oxidoreductase 1, and γ-glutamate cysteine ligase gene expressions and promoted catalase and glutathione peroxidase activities, which protected hepatocytes against PA-induced oxidative stress and lipotoxicity. Further investigation indicated that the molecular weight of MFP-II was 115.0 kDa, and MFP-II mainly consisted of galactose (30.5%), arabinose (26.2%), and rhamnose (23.1%). Overall, our research might provide in-depth insight into mulberry fruit polysaccharide in ameliorating lipid metabolic disorders.
研究领域:
药理学
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生物化学
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细胞生物学
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营养学
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产品关联
DOI
PubMed
高影响因子
Biomed Research International
·
2021
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IF 3.411
Ruixi Luo,Lifeng Zhao,Shuaishuai Li,Peng Chen,La Wang,Honghong Yu,Kun Cai,Qi Yu,Weiyi Tian
Excessive free fatty acid- (FFA-) induced endothelial lipotoxicity is involved in the pathogenesis of atherosclerosis. Endoplasmic reticulum (ER) stress is mechanistically related to endothelial lipotoxicity. Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is the major oxidatively modified low-density lipoprotein (OxLDL) receptor in endothelial cells and is highly abundant in atherosclerotic lesions. Curcumin reduces the LOX-1 expression; however, the mechanism underlying this effect remains unknown. In the current study, we explored whether curcumin ameliorates palmitic acid- (PA-) induced endothelial lipotoxicity and LOX-1 upregulation by reducing ER stress in human umbilical vein endothelial cells (HUVECs). We built endothelial lipotoxicity in vitro and found that LOX-1 was upregulated after PA stimulation, during which ER stress played an important role. Next, we observed that curcumin substantially alleviated PA-induced lipotoxicity by restoring cell viability, increasing angiogenesis, and decreasing lipid deposition. Furthermore, LOX-1 upregulation in HUVECs was blocked by curcumin, possibly via ER stress suppression. Overall, our findings demonstrated that curcumin alleviates endothelial lipotoxicity and LOX-1 upregulation, and ER stress inhibition may play a critical role in this effect.
研究领域:
心血管研究
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
Journal of Functional Foods
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2020
·
IF 3.701
Vemana Gowd,Lianghua Xie,Chongde Sun,Wei Chen
Bayberry (BB) fruits contain high levels of polyphenols and possess good bioactivities. However, there are no specific studies to illustrate the impact of human gut microbiota fermentation (HGMF) on BB polyphenols subjected to gastrointestinal digestion (GID). Therefore, in this study, BB was subjected to simulated GID and HGMF (0–48 h) in order to study the fate of BB bioactive components. Phenolic gut metabolites were identified and quantified by relevant standards using HPLC. Cyanidin-3- O -glucoside was the only anthocyanin in BB and could be detected in its free form even after gut fermentation for 24 h. Gut metabolites of BB showed better hypoglycemic activity by improving hepatic glucose consumption and glycogen content. Furthermore, gut metabolites significantly ameliorated glucolipotoxicity induced oxidative stress. Since BB gut metabolites showed good hypoglycemic and antioxidant activities, BB can be considered as a functional food and dietary supplementation of BB could help in maintenance of good health.
研究领域:
食品科学
·
营养学
·
药理学
·
微生物学
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产品关联
DOI
高影响因子
AQUACULTURE
·
2024
·
IF 3.9
Wenli Zhao,Yuedong Shen,Yangguang Bao,Óscar Monroig,Tingting Zhu,Peng Sun,Douglas R. Tocher,Qicun Zhou,Min Jin
Liver is considered the critical tissue for metabolic processing of dietary nutrients including lipids. High-fat diets (HFD) can induce hepatic lipotoxic injury, but the mechanism is unclear. This study aimed to elucidate the underlying role of endoplasmic reticulum stress (ERS) in mediating HFD-induced hepatic lipotoxic injury in black seabream ( Acanthopagrus schlegelii ) via in vitro and in vivo experiments. For the in vitro experiment, isolated hepatocytes from black seabream were incubated for 24 h in medium (Control), or medium supplemented with 200 μM oleic acid (OA) alone or in combination with 20 μM 4-phenyl butyric acid (OA + 4-PBA). In the in vivo experiment, black seabream juveniles (3.30 ± 0.10 g) were fed diets containing lipid at 12.4% (Control) or 18.6% (HFD) for 8 weeks, after which the HFD-fed fish were divided into three groups and, on alternate days over a period of 8 days, subjected to intraperitoneal injections of 50 mg/kg 4-PBA in hydroxypropyl-β-cyclodextrin (HBC) (treatment 4-PBA) or carrier alone (treatment HFD + HBC) versus no injection (HFD). The contents of triglyceride and non-esterified fatty acid, as well as expression levels of genes and proteins involved in lipid metabolism, ERS, apoptosis and inflammation were determined in liver and isolated hepatocytes, and oil-red O staining, ultrastructural observation, flow cytometry assay of apoptosis rate, and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay (TUNEL) staining were performed on hepatocytes. The in vitro experiment showed that 4-PBA treatment significantly decreased lipid accumulation, and the OA-induced expression levels of genes/proteins linked to ERS, lipogenesis, inflammation and apoptosis in hepatocytes. Transmission Electron Microscope (TEM) imaging showed that 4-PBA treatment mitigated the ER swelling induced by OA. These results were confirmed in the in vivo experiment, where 4-PBA injection reduced lipid deposition and expression levels of genes/proteins related to ERS, lipogenesis, inflammation and apoptosis in liver compared to the HFD treatment. In conclusion, these results confirmed that ERS plays a contributing regulatory role in HFD- and OA-induced lipotoxic damage including lipid accumulation, apoptosis and inflammation in liver and isolated hepatocytes of black seabream, which supply a new perspective in the cross-talk of ERS and hepatic lipotoxic damage in hepatocytes/liver of marine fish and provide theoretical guidance for the prevention and treatment of hepatic lipotoxic damage.
研究领域:
海洋生物学
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细胞生物学
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分子生物学
·
营养学
✓ 已验证
产品关联
DOI
高影响因子
International Heart Journal
·
2024
·
IF 1.2
Xiaoyu Shen,Jiamei Zhang,Zhou Zhou,Ruiqun Yu
Cardiomyocyte lipotoxicity and ferroptosis are the key to the development of diabetic cardiomyopathy (DCM). Perilipin 5 (PLIN5) is perceived as a significant target of DCM. This study aimed to focus on the role and mechanism of PLIN5 on lipotoxicity and ferroptosis in DCM.Following transfection, mouse cardiomyocytes HL-1 were induced by 0.1 mM palmitic acid (PA) to set up lipotoxic cardiomyocyte models. The cell viability and lipid accumulation were evaluated by cell counting kit-8 assay and Oil red O staining, respectively. Ferrous ion (Fe2+), glutathione (GSH), malondialdehyde (MDA), and reactive oxygen species (ROS) levels were determined to verify the effects of PLIN5 or Pirin (PIR) on ferroptosis. Quantitative real-time reverse transcription polymerase chain reaction or Western blot was performed for quantitative analysis.PLIN5 overexpression promoted the viability, GSH level, and expression of GPX4/PIR/intracellular P65, yet suppressed lipid accumulation, level of Fe2+/MDA/ROS, and expression of interleukin (IL) -1β/IL-18/intranuclear P65 in PA-stimulated HL-1 cells. PIR silencing counteracted the roles of PLIN5 overexpression in PA-stimulated HL-1 cells.PLIN5 suppresses lipotoxicity and ferroptosis in cardiomyocyte via modulating PIR/NF-κB axis, hinting its potential as a therapeutic target in DCM.
研究领域:
心脏病学
·
细胞生物学
·
分子生物学
·
糖尿病
·
病理学
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产品关联
DOI
PubMed
高影响因子
Nutrition & Metabolism
·
2020
·Vol. 17
·期 1
·1-14
·
IF 3.211
Zeng Xin,Zhu Min,Liu Xiaohong,Chen Xuanmin,Yuan Yujia,Li Lan,Liu Jingping,Lu Yanrong,Cheng Jingqiu,Chen Younan
Background Pyroptosis is a novel programmed cell death. It is identified as caspase-1 dependent and characterized by plasma-membrane rupture and release of proinflammatory intracellular contents inculuding IL-1 beta and IL-18. Pyroptosis is distinct from other forms of cell death, especially apoptosis that is characterized by nuclear and cytoplasmic condensation and is elicited via activation of a caspase cascade. In pyroptosis, gasdermin D (GSDMD) acts as a major executor, while NLRP3 related inflammasome is closely linked to caspase-1 activation. Given that pyroptosis has played a critical role in the progression of non-alcoholic steatohepatitis (NASH), here, we investigated whether the regulation of pyroptosis activation is responsible for the protective role of monounsaturated oleic acids in the context of hepatocellular lipotoxicity.Methods Human hepatoma cell line HepG2 cells were exposed to palmitic acid (PA) with or without oleic acids (OA) or/and endoplasmic reticulum (ER) stress inhibitor tauroursodeoxycholic acid (TUDCA) for 24 h. Besides, the cells were treated with the chemical ER stressor tunicamycin (TM) with or without OA for 24 h as well. The expressions of pyroptosis and ER stress related genes or proteins were determined by real-time PCR, Western blot or immunofluorescence. The morphology of pyroptosis was detected by acridine orange and ethidium bromide (AO/EB) staining. The release of IL-1 beta and tumor necrosis factor alpha (TNF-α) was determined by ELISA. Sprague–Dawley (SD) rats were fed with high fat diet (HFD) for 16 w, then, HFD was half replaced by olive oil to observe the protective effects of olive oil. The blood chemistry were analyzed, and the liver histology and the expressions of related genes and proteins were determined in the liver tissues.Results We demonstrated that PA impaired the cell viability and disturbed the lipid metabolism of HepG2 cells (P < 0.01), but OA robustly rescued cells from cell death (P < 0.001). More importantly, we found that instead of cell apoptosis, PA induced significant pyroptosis, evidenced by remarkably increased mRNA and protein expressions of inflammasome marker NLRP3, Caspase-1 and IL-1beta, as well as cell membrane perforation driving protein GSDMD (P < 0.05). Furthermore, we demonstrated that the PA stimulated ER stress was causally related to pyroptosis. The enhanced expressions of ER stress markers CHOP and BIP were found subcellular co-located to pyroptosis markers NLRP3 and ASC. Additionally,TM was able to induce pyroptosis like PA did, and ER stress inhibitor TUDCA was able to inhibit both PA and TM induced ER stress as well as pyroptosis. Furthermore, we demonstrated that OA substantially alleviated either PA or TM induced ER stress and pyroptosis in HepG2 cells (P < 0.01). In vivo, only olive oil supplementation did not cause significant toxicity, while HFD for 32 w obviously induced liver steatosis and inflammation in SD rats (P < 0.05). Half replacement of HFD with olive oil (a mixed diet) has remarkably ameliorated liver abnormalities, and particularly inhibited the protein expressions of either ER stress and pyroptosis markers (P < 0.05).Conclusion Palmitic acid induced predominant pyroptosis in HepG2 cells, and ER stress may be responsible for the induction of pyroptosis and subsequent cell death. Monounsaturated oleic acids were able to ameliorate hepatocellular lipotoxicity both in vitro and in vivo, and OA mediated inhibition of ER stress and pyroptosis may be the underlying mechanisms.
研究领域:
药理学
·
细胞生物学
·
肝病学
·
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）