Nutrients
·
2016
·Vol. 8
·期 12
·799
·
IF 3.759
Shu-Fang Xia,Guo-Wei Le,Peng Wang,Yu-Yu Qiu,Yu-Yu Jiang,Xue Tang
Myricetin is an effective antioxidant in the treatment of obesity and obesity-related metabolic disorders. The objective of this study was to explore the regressive effect of myricetin on pre-existing hepatic steatosis induced by high-fat diet (HFD). C57BL/6 mice were fed either a standard diet or a HFD for 12 weeks and then half of the mice were treated with myricetin (0.12% in the diet,w/w) while on their respective diets for further 12 weeks. Myricetin treatment significantly alleviated HFD-induced steatosis, decreased hepatic lipid accumulation and thiobarbituric acid reactive substance (TBARS) levels, and increased antioxidative enzyme activities, including catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities. Microarray analysis of hepatic gene expression profiles showed that myricetin significantly altered the expression profiles of 177 genes which were involved in 12 biological pathways, including the peroxisome proliferator activated receptor (PPAR) signaling pathway and peroxisome. Further research indicated that myricetin elevated hepatic nuclear Nrf2 translocation, increased the protein expression of heme oxygenase-1 (HO-1) and NAD(P)H quinone dehydrogenase 1 (NQO1), reduced the protein expression of PPARγ, and normalized the expressions of genes that were involved in peroxisome and the PPAR signaling pathway. Our data indicated that myricetin might represent an effective therapeutic agent to treat HFD-induced hepatic steatosis via activating the Nrf2 pathway and the PPAR signaling pathway.Keywords:myricetin;hepatic steatosis;Nrf2;PPARγ;oxidative stress
研究领域:
药理学
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分子生物学
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营养学
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产品关联
DOI
PubMed
高影响因子
PLANTA MEDICA
·
2020
·Vol. 86
·期 04
·255-266
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IF 2.687
Nan Xu,Xue Wu,Hui-Juan Luo,Fang-Fang Xu,Qiong-Hui Huang,Jia-Zhen Wu,Yu-Xuan Gan,Min-Yao Li,Zheng-Quan Lai,Hui-Ran Lin,Jian-Nan Chen,Zi-Ren Su,Wei-Peng Ai,Yu-Hong Liu
Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases worldwide. Nevertheless, no first-line therapy exists. Hepatic steatosis is the earliest stage of NAFLD, which is characterized by an accumulation of hepatic lipids. Patchouli oil (PO), which is isolated from the well-known Chinese herb named Pogostemon cablin (Blanco) Benth. (Lamiaceae), inhibits hepatic lipid accumulation effectively. However, its potential ability for the treatment of NAFLD had not been reported before. Thus, the objective of this study was to investigate the effectiveness of PO against hepatic steatosis and its underlying mechanisms. We used a high fat diet (HFD)-induced hepatic steatosis model of rats to estimate the effect of PO against NAFLD. Hematoxylin-eosin and oil red O staining were used to analyze the hepatic histopathological changes. ELISA, RT-qPCR, and Western blotting analysis were applied to evaluate the parameters for hepatic steatosis. Our results showed that PO significantly attenuated the lipid profiles and the serum enzymes, evidenced by quantitative and histopathological analyses. It also markedly down-regulated the expression of sterol regulatory element-binding protein 1 (SREPB-1c) with its downstream factors in de novo lipogenesis. And, likewise, in lipid export by very low-density lipoproteins (VLDL), related molecules were dramatically improved. Furthermore, PO observably normalized the aberrant peroxisome proliferator-activated receptor α (PPAR-α) signal in fatty acids oxidation. In conclusion, PO exerted a preventing effect against HFD-induced steatosis and might be due to decrease de novo lipogenesis, promote export of lipids, as well as owing to improve fatty acids oxidation.
研究领域:
药理学
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肝病学
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代谢性疾病
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DOI
PubMed
高影响因子
Journal of Functional Foods
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2025
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IF 4
Yan Ma,Zhengnan Jiang,Hai Xie,Jian Wang,Minni Li,Huifang Ge,Wenbin Li,Zhongwen Xie,Daxiang Li,Xueling Gao,Hongyan Wang
Fermented oxidation fresh tea (FOFT) is a unique dark tea produced by a single strain of Eurotium cristatum , and its impact on obesity has not been extensively studied. Here, we investigated the anti-obesity and metabolic benefits of FOFT using a HFD-induced obesity mouse model. The HFD-fed mice or ND-fed mice were orally administered with FOFT for 12 weeks. The results showed that FOFT invention significantly suppressed body weight gain, ameliorated liver and adipocyte morphology, and improved glucolipid metabolism and intestinal homeostasis imbalance in HFD-fed mice. Notably, FOFT administration caused no adverse effects in ND mice, indicating its safety at tested doses. Moreover, FOFT restored intestinal microbiome dysbiosis and elevated the short-chain fatty acid levels. This gut microbiome shift was associated with reduced systemic inflammation and attenuated hepatic lipid accumulation. These findings suggest that FOFT, as a novel functional food, holds great promise for resistance to obesity and its comorbidities.
研究领域:
营养学
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微生物学
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代谢生物学
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DOI
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
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2025
·
IF 4.7
Weiting Hu,Wenyu Gong,Fan Yang,Rui Cheng,Gerong Zhang,Lu Gan,Yikun Zhu,Weiwei Qin,Ying Gao,Xing Li,Jing Liu
Tirzepatide is a dual agonist of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors and is a promising therapeutic option for type 2 diabetes mellitus (T2DM). Nevertheless, its effect and underlying mechanism on hepatic steatosis remain ambiguous. Herein, we explored the impact of tirzepatide on improving hepatic steatosis in diabetic mice, with a particular focus on the gut microbiota and bile acids (BAs) using animal models. The tirzepatide effectively reduced body weight, improved insulin resistance, decreased serum and hepatic lipid levels, and mitigated liver injury. Compared to semaglutide, tirzepatide exhibited superior efficacy in reducing hepatic lipid accumulation. 16S rRNA gene sequencing and targeted metabolomics of BAs revealed that tirzepatide ameliorated gut microbiota dysbiosis and BAs metabolism in diabetic mice. Notably, tirzepatide observably increased the abundance of beneficial genera such as Akkermansia , elevated the ratio of farnesoid X receptor (FXR) antagonists (glycoursodeoxycholic acid: GUDCA, β-muricholic acid: β-MCA, hyodeoxycholic acid: HDCA, ursodeoxycholic acid: UDCA) to natural agonists (cholic acid: CA, lithocholic acid: LCA, chenodeoxycholic acid: CDCA, glycocholic acid: GCA, taurodeoxycholic acid: TDCA), and reduced FXR expression in intestinal tissues. In conclusion, tirzepatide attenuated hepatic steatosis in diabetic mice and regulated the gut microbiota and BAs metabolism, which may help to provide a novel therapeutic approach and therapeutic target for metabolic dysfunction-associated steatotic liver disease (MASLD).
研究领域:
药理学
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代谢组学
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微生物学
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产品关联
DOI
PubMed
高影响因子
Nutrients
·
2023
·Vol. 15
·期 14
·3200
·
IF 5.9
Wen Liu,Min Zhu,Meng Gong,Wen Zheng,Xin Zeng,Qing Zheng,Xiaoyu Li,Fudong Fu,Yingyi Chen,Jingqiu Cheng,Zhiyong Rao,Yanrong Lu,Younan Chen
Obesity is a recognized epidemic worldwide, and the accumulation of excess free saturated fatty acids (SFAs) in cells induces cellular lipotoxic damage and increases the risk of a wide spectrum of metabolic diseases including type 2 diabetes (T2D) and nonalcoholic fatty liver disease (NAFLD). Monounsaturated fatty acids (MUFAs) and polyunsaturated fatty acids (PUFAs) have been reported to combat SFA-induced cellular damage. However, the comparative studies of the two types of unsaturated fatty acids (UFAs) are still limited. We investigated the effects of different MUFAs and PUFAs in the human hepatocyte line L-02 cells in vitro, and in high-fat-diet (HFD)-induced obese C57BL/6 mice in vivo. The results of the in vitro study showed that SFAs induced significant cellular lipotoxic damage, but the combination of MUFAs/PUFAs with SFAs significantly improved the impaired cell viability. Particularly, oleic acid (OA) was superior to eicosapentaenoic acid (EPA), Docosahexaenoic acid (DHA), and arachidonic acid (AA) in terms of its anti-apoptotic effect and inhibition of endoplasmic reticulum (ER) stress. In vivo, both olive-oil-enriched (HFD + OO) and fish-oil-enriched high-fat diets (HFD + FO) reduced hepatic steatosis and improved insulin sensitivity in obese mice. However, FO induced an abnormal increase in serum aspartate aminotransferase (AST) and an increase in the oxidative stress indicator Malondialdehyde (MDA). Liver-targeted lipidomic analysis showed that liver lipid metabolites under the two types of UFA dietary interventions differed from the HFD group, modulating the abundance of some lipid metabolites such as triglycerides (TGs) and glycerophospholipids. Furthermore, the FO diet significantly increased the abundance of the associated FA 20:5 long-chain lipid metabolites, whereas the OO diet regulated the unsaturation of all fatty acids in general and increased the abundance of FA 18:1 in the overall lipid metabolites, especially TGs, which may primarily contribute to the FO, and OO drove protection in NAFLD.Keywords:obesity;insulin resistance;hepatic steatosis;unsaturated fatty acids;targeted lipidomics
研究领域:
营养学
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代谢学
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脂质生物学
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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 Animal Science and Biotechnology
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2024
·Vol. 15
·期 1
·1-18
·
IF 6.3
Liu Min,Kang Zeyue,Cao Xikang,Jiao Hongchao,Wang Xiaojuan,Zhao Jingpeng,Lin Hai
Background This work aimed to investigate the potential benefits of administering Prevotella and its primary metabolite succinate on performance, hepatic lipid accumulation and gut microbiota in laying hens.Results One hundred and fifty 58-week-old Hyline Brown laying hens, with laying rate below 80% and plasma triglyceride (TG) exceeding 5 mmol/L, were used in this study. The hens were randomly allocated into 5 groups and subjected to one of the following treatments: fed with a basal diet (negative control, NC), oral gavage of 3 mL/hen saline every other day (positive control, PC), gavage of 3 mL/hen Prevotella melaninogenica (107 CFU/mL, PM) or 3 mL/hen Prevotella copri (107 CFU/mL, P. copri) every other day, and basal diet supplemented with 0.25% sodium succinate (Succinate). The results showed that PM and P. copri treatments significantly improved laying rate compared to the PC (P < 0.05). The amount of lipid droplet was notably decreased by PM, P. copri, and Succinate treatments at week 4 and decreased by P. copri at week 8 (P < 0.05). Correspondingly, the plasma TG level in Succinate group was lower than that of PC (P < 0.05). Hepatic TG content, however, was not significantly influenced at week 4 and 8 (P > 0.05). PM treatment increased (P < 0.05) the mRNA levels of genes PGC-1β and APB-5B at week 4, and ACC and CPT-1 at week 8. The results indicated enhanced antioxidant activities at week 8, as evidenced by reduced hepatic malondialdehyde (MDA) level and improved antioxidant enzymes activities in PM and Succinate groups (P < 0.05). Supplementing with Prevotella or succinate can alter the cecal microbiota. Specifically, the abundance of Prevotella in the Succinate group was significantly higher than that in the other 4 groups at the family and genus levels (P < 0.05).Conclusion sOral intake of Prevotella and dietary supplementation of succinate can ameliorate lipid metabolism of laying hens. The beneficial effect of Prevotella is consistent across different species. The finding highlights that succinate, the primary metabolite of Prevotella, represents a more feasible feed additive for alleviating fatty liver in laying hens.
研究领域:
动物科学
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营养学
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微生物学
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产品关联
DOI
PubMed
高影响因子
ISME Journal
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2025
·
IF 10
Wei Yusen,Mao Jiangdi,Tang Wenjie,Ma Yanfei,Li Jiachen,Su Songtao,Ni Zhixiang,Wu Jinhong,Liu Daren,Wang Haifeng
Male offspring with intrauterine growth restriction exhibit more pronounced hepatic lipid metabolism abnormalities than females, necessitating earlier intervention. Icariin has been shown to effectively modulate hepatic lipid metabolism in male piglets with intrauterine growth restriction. However, the role of gut microbiota in this process remains to be elucidated. This study aimed to explore the influence of gut microbiota on icariin-induced enhancement of hepatic lipid metabolism. By examining changes in microbiota composition and hepatic lipid metabolism following icariin intervention, the study demonstrated an association between microbial alterations and hepatic lipid regulation through fecal microbiota transplantation. The impact of Catenibacterium on gut microbiota structure and hepatic lipid metabolism was assessed in vivo, and the direct effect of icariin on Catenibacterium was explored in vitro. Results revealed that icariin intervention modified fecal, ileal, and colonic microbiota in male piglets with intrauterine growth restriction, enhanced gut morphology and barrier function, and normalized the expression of hepatic peroxisome proliferator-activated receptor (PPAR) signaling pathway-related genes. Fecal microbiota transplantation from piglets with intrauterine growth restriction impaired intestinal barrier function and led to hepatic lipid deposition, whereas transplantation from icariin-treated donors showed no pathological changes, an outcome associated with reduced abundance of Catenibacterium. Mechanistically, icariin inhibits adenosine triphosphate synthesis to suppress Catenibacterium, remodels gut microbiota, reduces lipopolysaccharide production and translocation, and activates the hepatic PPARα/CD36 axis. In conclusion, icariin intervention alleviates hepatic lipid metabolic disorders in male offspring with intrauterine growth restriction by suppressing Catenibacterium, restoring gut microbial balance, and enhancing intestinal barrier integrity to limit lipopolysaccharide translocation.
研究领域:
微生物学
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药理学
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营养学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Toxins
·
2021
·Vol. 13
·期 11
·802
·
IF 4.546
Qian-Wen Zheng,Xu-Fen Ding,Hui-Jun Cao,Qian-Zhi Ni,Bing Zhu,Ning Ma,Feng-Kun Zhang,Yi-Kang Wang,Sheng Xu,Tian-Wei Chen,Ji Xia,Xiao-Song Qiu,Dian-Zhen Yu,Dong Xie,Jing-Jing Li
Ochratoxin A(OTA) is considered to be one of the most important contaminants of food and feed worldwide. The liver is one of key target organs for OTA to exert its toxic effects. Due to current lifestyle and diet, nonalcoholic fatty liver disease (NAFLD) has been the most common liver disease. To examine the potential effect of OTA on hepatic lipid metabolism and NAFLD, C57BL/6 male mice received 1 mg/kg OTA by gavage daily. Compared with controls, OTA increased lipid deposition and TG accumulation in mouse livers. In vitro OTA treatment also promoted lipid droplets accumulation in primary hepatocytes and HepG2 cells. Mechanistically, OTA prevented PPARγ degradation by reducing the interaction between PPARγ and its E3 ligase SIAH2, which led to activation of PPARγ signaling pathway. Furthermore, downregulation or inhibition of CD36, a known of PPARγ, alleviated OTA-induced lipid droplets deposition and TG accumulation. Therefore, OTA induces hepatic steatosis via PPARγ-CD36 axis, suggesting that OTA has an impact on liver lipid metabolism and may contribute to the development of metabolic diseases.Keywords:fatty liver disease;lipid metabolism;OTA;PPARKey Contribution:The in vitro and in vivo study reveal that OTA induces hepatic steatosis via PPARγ-CD36 axis. OTA prevents PPARγ from ubiquitination-mediated degradation by reducing the expression of the E3 ligase SIAH2 and SIAH2-PPARγ interaction.
研究领域:
毒理学
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肝病学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PLoS One
·
2024
·Vol. 19
·期 3
·e0301133
·
IF 2.9
Suye Ran,Lingyu Song,Hong Yang,Jiangnan Yu,Yunhuan Zhen,Qi Liu
Purpose
Nonalcoholic steatohepatitis (NASH) is the progressive form of nonalcoholic fatty liver disease (NAFLD), which has a high risk of cirrhosis, liver failure, and hepatocellular carcinoma. Piperine (Pip) is an extract of plants with powerful anti-inflammatory effects, however, the function of Pip in NASH remains elusive. Here, we aim to explore the role of Pip in NASH and to find the possible mechanisms.
Methods
Methionine and choline-deficient (MCD) diets were used to induce steatohepatitis, methionine- and choline-sufficient (MCS) diets were used as the control. After Pip treatment, H&E staining, Oil Red O staining, hepatic triglyceride (TG) content and F4/80 expression were performed to analysis liver steatosis and inflammation; Masson’s staining, COL1A1 and α-SMA were detected liver fibrosis. Lipopolysaccharide (LPS) -treated AML12 cells were used to as the cell model to induce pyroptosis. Then, pyroptosis-related proteins, IL-1β and LDH release were detected in vivo and in vitro . Finally, NF-κB inhibitor, BAY11-7082, was used to further demonstrate the mechanism of Pip in NASH.
Results
The study found that Pip alleviated liver steatosis, inflammation, hepatocyte injury, and fibrosis in mice fed with MCD diets. Moreover, the pyroptosis markers (NLRP3, ASC, caspase-1 p20, and GSDMD), IL-1β and LDH release were decreased by Pip treatment. NF-κB activation was suppressed by Pip treatment and pyroptosis-related proteins were down regulated by BAY11-7082.
Conclusion
Pip ameliorates NASH progression, and the therapeutical effect was associated with inhibition of hepatocyte pyroptosis induced by NF-κB.
研究领域:
药理学
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肝病学
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免疫学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF IMAGING SYSTEMS AND TECHNOLOGY
·
2024
·Vol. 34
·期 4
·e23123
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IF 3
Yuqiu Fu,Deyue Zang,Baiyou Lin,Qiming He,Yujie Xie,Baoliang Zhang,Yao Liu,Yi Jin,Yonghong He,Tian Guan
Nonalcoholic fatty liver disease (NAFLD) is a prevalent liver disorder affecting approximately 25.2% of the global population, posing risks of liver fibrosis, cancer, and metabolic disturbances. Despite its increasing prevalence, many facets of NAFLD's pathogenesis remain elusive, and there are currently no approved therapeutic drugs, underscoring the critical need for a comprehensive understanding of its pathophysiology to enable early diagnosis and intervention. Experimental animal studies play a pivotal role in elucidating the mechanisms underlying NAFLD and in the exploration of novel pharmacotherapies. Despite the widespread integration of deep learning techniques in human histopathology, their application to scrutinize histological features in animal models warrants exploration. This study presents a pioneering NAFLD assessment system leveraging IFNet and ResNet34 architectures. This automated system adeptly identifies inflammatory cell foci and hepatic steatosis in histopathology sections of rat livers. Remarkably, our approach achieved an impressive 95.6% accuracy in the assessment of hepatic steatosis and 77.7% in the evaluation of inflammation cell foci. By introducing a novel histopathology scoring system, our methodology mitigated subjective variations inherent in traditional pathologist evaluations, concurrently streamlining time and labor costs. This system ensured a standardized and precise assessment of rat liver histology in NAFLD and represented a significant stride toward enhancing the efficiency and objectivity of experimental outcomes.
研究领域:
病理学
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医学影像分析
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实验动物模型
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肝脏疾病研究
✓ 已验证
产品关联
DOI
高影响因子
Frontiers in Endocrinology
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2023
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IF 5.2
Tingwan Du,Lian Xiang,Jingjing Zhang,Chunmei Yang,Wenxin Zhao,Jialu Li,Yong Zhou,Ling Ma
Introduction The study aimed to explore the association of serum 25(OH)D 3 and hepatic steatosis in non-alcoholic fatty liver disease (NAFLD) patients and to determine whether the effect of vitamin D (VD) is mediated by activation of the peroxisome proliferator-activated receptor α (PPARα) pathway. Methods The study contained a case-control study, in vivo and in vitro experiments. A case-control study was conducted to compare serum parameters between NAFLD patients and controls and to evaluate the association of 25(OH)D 3 and NAFLD. In vivo study, male Wistar rats were randomly divided into control and model groups, fed a standard chow diet and a high-fat diet (HFD), respectively, for 7 weeks to generate an NAFLD model. Then, the rats were treated with VD and a PPARα antagonist (MK886) for 7 weeks. Tissue and serum were collected and assessed by biochemical assays, morphological analysis, histological analysis, and western blot analysis. In vitro , HepG2 cells were incubated with oleic acid (OA) to induce steatosis, which was evaluated by staining. HepG2 cells were pretreated with MK886 followed by calcitriol treatment, and differences in lipid metabolism-related proteins were detected by western blot. Results NAFLD patients were characterized by impaired liver function, dyslipidemia, and insulin resistance. Serum 25(OH)D 3 was negatively associated with alanine aminotransferase (ALT) in NAFLD. VD deficiency was a risk factor for patients with no advanced fibrosis. Adequate VD status (25(OH)D 3 >20 ng/mL) had a protective effect in patients after adjustment for confounding variables. NAFLD rats showed hyperlipidemia with severe hepatic steatosis, systematic inflammation, and lower serum 25(OH)D 3 . VD treatment ameliorated hepatic steatosis both in NAFLD rats and OA-induced HepG2 cells. Further, MK886 inhibited the anti-steatosis effect of VD. Conclusion The study revealed that an adequate VD level may act as a protective factor in NAFLD and that VD may alleviate hepatic steatosis via the PPARα signaling pathway.
研究领域:
肝病学
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内分泌学
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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
Food Bioscience
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2023
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IF 5.2
Hengju Ge,Jiaxin Li,Yang Xu,Jiahong Xie,Naymul Karim,Fujie Yan,Jianling Mo,Wei Chen
Curcumin (CUR), the main compound extracted from Curcuma longa , has various biological actions, including hepatoprotective, anti-infective, anti-inflammatory, antioxidant, and neurotrophic properties. But it has not yet been clarified how CUR affects the accumulation of fatty in hepatic cells. Our study uncovered that CUR decreased the lipid deposition in free fat acids (FFAs)-treated hepatocytes, which could be blocked by Compound C (an AMPK inhibitor). This result suggests that protective effect was associated with the AMPK pathway activation. MiR-3666 directly targets the AMPK gene, and overexpression of miR-3666 greatly weakens the hypolipidemic effect of CUR. Our results showed that CUR reduced FFAs-induced lipid deposition by targeting miR-3666. This boosted AMPK phosphorylation and inhibited its downstream targets, including ACC and SREBP1 . These findings together confirm that CUR-mediated inhibition of miR-3666 to activate the AMPK pathway is a potential alternative for alleviation of hepatic lipid deposition.
研究领域:
药理学
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分子生物学
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肝病学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）