scholarly journals Ochratoxin A Induces Steatosis via PPARγ-CD36 Axis

Toxins ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 802
Author(s):  
Qian-Wen Zheng ◽  
Xu-Fen Ding ◽  
Hui-Jun Cao ◽  
Qian-Zhi Ni ◽  
Bing Zhu ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Liver Disease ◽  
Ochratoxin A ◽  
Lipid Droplets ◽  
Metabolic Diseases ◽  
Liver Lipid ◽  
Potential Effect ◽  
Nonalcoholic Fatty Liver ◽  
Food And Feed

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.

scholarly journals Liraglutide Attenuates Nonalcoholic Fatty Liver Disease through Adjusting Lipid Metabolism via SHP1/AMPK Signaling Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Peng Yu ◽  
Xi Xu ◽  
Jing Zhang ◽  
Xuan Xia ◽  
Fen Xu ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Hepg2 Cells ◽  
Fatty Liver Disease ◽  
Nonalcoholic Fatty Liver ◽  
Ampk Signaling

A glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide (LR) had been experimentally and clinically shown to ameliorate nonalcoholic fatty liver disease (NAFLD). This study aimed to investigate the beneficial effect of LR on NAFLD in vivo and in vitro and its underlying molecular mechanism. The effects of LR were examined on the high-fat diet-induced in vivo model in mice and in vitro model of NAFLD in human HepG2 cells. Liver tissues and HepG2 cells were procured for measuring lipid metabolism, histological examination, and western blot analysis. LR administration significantly lowered the serum lipid profile and lipid disposition in vitro and in vivo because of the altered expression of enzymes on hepatic gluconeogenesis and lipid metabolism. Moreover, LR significantly decreased Src homology region 2 domain-containing phosphatase-1 (SHP1) and then increased the expression of phosphorylated-AMP-activated protein kinase (p-AMPK). However, the overexpression of SHP1 mediated by lentivirus vector reversed LR-induced improvement in lipid deposition. Moreover, SHP1 silencing could further increase the expression of p-AMPK to ameliorate lipid metabolism and relative lipogenic gene induced by LR. In addition, abrogation of AMPK by Compound C eliminated the protective effects of LR on lipid metabolism without changing the expression of SHP1. LR markedly prevented NAFLD through adjusting lipid metabolism via SHP1/AMPK signaling pathway.

scholarly journals Quercitrin Ameliorates Hyperlipidemia and Hepatic Steatosis in Ovariectomized Mice

Life ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 243
Author(s):  
Haeng Jeon Hur ◽  
Yeon-Hui Jeong ◽  
Sang Hee Lee ◽  
Mi Jeong Sung
Keyword(s):  
Lipid Metabolism ◽  
Postmenopausal Women ◽  
Hepatic Steatosis ◽  
Metabolic Diseases ◽  
Liver Lipid ◽  
Density Lipoprotein ◽  
Estrogen Deficiency ◽  
Protective Effects ◽  
Nonalcoholic Fatty Liver ◽  
Ovariectomized Mice

Nonalcoholic fatty liver disease (NAFLD) is associated with progressive metabolic diseases. Estrogen deficiency increases the NAFLD risk among postmenopausal women. Thus, effective agents to prevent and treat NAFLD in postmenopausal women are required. Quercitrin (Quer) is a natural glycosylated flavonoid with antimicrobial, anti-inflammatory, and hypolipidemic effects. This study investigated whether Quer improves dysregulated lipid metabolism and suppresses hepatic steatosis in ovariectomized (OVX) mice as an experimental model mimicking postmenopausal women. Mice were assigned to the following four groups: SHAM, OVX, OVX + β-estradiol (0.4 mg/kg diet), and OVX + Quer (500 mg/kg diet). Mice were administered a diet with or without Quer for three months. OVX mice displayed significantly higher body mass, epidermal fat, and liver weights than those of SHAM mice. However, these levels were reduced in Quer-treated mice. Quer treatment reduced the levels of serum lipid metabolites, including triglycerides, total cholesterol, and low-density lipoprotein cholesterol. Furthermore, Quer reduced liver lipid steatosis and inhibited the expression of proinflammatory cytokines, such as tumor necrosis factor-α, IL-6, and IL-1β. The results of the present study indicate that Quer improves dysregulated lipid metabolism and reduces hepatic steatosis and inflammation by compensating for estrogen deficiency, suggesting that Quer may potentially exert protective effects during hepatic steatosis in postmenopausal women.

scholarly journals Transcriptomic Analysis Reveals the Protective Effects of Empagliflozin on Lipid Metabolism in Nonalcoholic Fatty Liver Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Yuting Ma ◽  
Chengxia Kan ◽  
Hongyan Qiu ◽  
Yongping Liu ◽  
Ningning Hou ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Transcriptome Analysis ◽  
Fatty Liver Disease ◽  
Liver Lipid ◽  
Gene Set Enrichment Analysis ◽  
Nonalcoholic Fatty Liver ◽  
Sodium Glucose Cotransporter

Empagliflozin is a novel type of sodium-glucose cotransporter two inhibitor with diverse beneficial effects in the treatment of nonalcoholic fatty liver disease (NAFLD). Although empagliflozin impacts NAFLD by regulating lipid metabolism, the underlying mechanism has not been fully elucidated. In this study, we investigated transcriptional regulation pathways affected by empagliflozin in a mouse model of NAFLD. In this study, NAFLD was established in male C57BL/6J mice by administration of a high-fat diet; it was then treated with empagliflozin and whole transcriptome analysis was conducted. Gene expression levels detected by transcriptome analysis were then verified by quantitative real-time polymerase chain reaction, protein levels detected by Western Blot. Differential expression genes screened from RNA-Seq data were enriched in lipid metabolism and synthesis. The Gene Set Enrichment Analysis (GSEA) results showed decreased lipid synthesis and improved lipid metabolism. Empagliflozin improved NAFLD through enhanced triglyceride transfer, triglyceride lipolysis and microsomal mitochondrial β-oxidation. This study provides new insights concerning the mechanisms by which sodium-glucose cotransporter two inhibitors impact NAFLD, particularly in terms of liver lipid metabolism. The lipid metabolism-related genes identified in this experiment provide robust evidence for further analyses of the mechanism by which empagliflozin impacts NAFLD.

scholarly journals miR-26a Potentially Contributes to the Regulation of Fatty Acid and Sterol Metabolism In Vitro Human HepG2 Cell Model of Nonalcoholic Fatty Liver Disease

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Omaima Ali ◽  
Hebatallah A. Darwish ◽  
Kamal M. Eldeib ◽  
Samy A. Abdel Azim
Keyword(s):  
Fatty Acid ◽  
Lipid Metabolism ◽  
Liver Disease ◽  
Fatty Liver ◽  
Er Stress ◽  
Hepg2 Cells ◽  
Fatty Liver Disease ◽  
Mrna Levels ◽  
Nonalcoholic Fatty Liver

Nonalcoholic fatty liver disease (NAFLD) is a metabolic-related disorder ranging from steatosis to steatohepatitis, which may progress to cirrhosis and hepatocellular carcinoma (HCC). This study aimed at assessing the regulatory and protective role of miR-26a on lipid metabolism and progression of NAFLD in human HepG2 cells loaded with free fatty acids (FFA). Lentivirus expressing miR-26a or negative control miR was used to transduce HepG2 cells and to establish stable cell lines. Gain or loss of function using an miR-26a inhibitor was used to compare triglyceride content (TG), total cholesterol level (CL), total antioxidant capacity (TAC), malondialdehyde (MDA) and the level of apoptosis. In addition, quantitative reverse transcription polymerase chain reaction (qPCR) was used to assess the mRNA levels of lipogenesis, TG synthesis, storage genes, inflammatory and fibrogenic markers, and autophagic besides endoplasmic reticulum (ER) stress markers after gaining or losing the function of miR-26a. miR-26a levels decreased in response to FFA in human HepG2 cells. After the establishment of a stable cell line, the upregulation of miR-26a resulted in the downregulation of TG, CL, and MDA levels, through regulating mRNA levels of genes involved in lipid homeostasis, ER stress marker, inflammatory and fibrogenic markers. Nevertheless, there was a marked increment in the mRNA expression of autophagic marker genes. Moreover, miR-26a overexpression protects the cells from apoptosis, whereas inhibition of miR-26a, using an anti-miR-26a oligonucleotide, decreased the expression of miR-26a which potentially contributes to altered lipid metabolism in HepG2 cells loaded with FFA. In conclusion, these findings suggested that miR-26a has a crucial role in regulating fatty acid and cholesterol homeostasis in HepG2 cells, along with the offered protection against the progression of NAFLD in vitro. Hence, miRNAs could receive growing attention as useful noninvasive diagnostic markers to follow the progression of NAFLD and to identify novel therapeutic targets.

scholarly journals Silencing of functional p53 attenuates NAFLD by promoting HMGB1-related autophagy induction

2020 ◽  
Vol 14 (5) ◽  
pp. 828-841
Author(s):  
Xuequn Zhang ◽  
Yiming Lin ◽  
Sisi Lin ◽  
Chunxiao Li ◽  
Jianguo Gao ◽  
...  
Keyword(s):  
Liver Disease ◽  
Metabolic Diseases ◽  
High Mobility ◽  
Cell Models ◽  
Tumor Suppressor P53 ◽  
Nonalcoholic Fatty Liver ◽  
Autophagy Induction ◽  
Huh7 Cells

Abstract Background and aim Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease worldwide, but its pathogenesis remains imprecisely understood and requires further clarification. Recently, the tumor suppressor p53 has received growing attention for its role in metabolic diseases. In this study, we performed in vivo and in vitro experiments to identify the contribution of p53–autophagy regulation to NAFLD. Methods Livers from wild-type and p53 knockout mice as well as p53-functional HepG2 cells and p53-dysfunctional Huh7 cells were examined for autophagy status and HMGB1 translocation. In vivo and in vitro NAFLD models were established, and steatosis was detected. In the cell models, autophagy status and steatosis were examined by p53 and/or HMGB1 silencing. Results First, the silencing of p53 could induce autophagy both in vivo and in vitro. In addition, p53 knockout attenuated high-fat diet-induced NAFLD in mice. Similarly, knockdown of p53 could alleviate palmitate-induced lipid accumulation in cell models. Furthermore, high mobility group box 1 (HMGB1) was proven to contribute to the effect of silencing p53 on alleviating NAFLD in vitro as an autophagy regulator. Conclusion The anti-NAFLD effect of functional p53 silencing is associated with the HMGB1-mediated induction of autophagy. Graphic abstract

scholarly journals RYGB increases postprandial gastric nesfatin-1 and rapid relieves NAFLD via gastric nerve detachment

PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0243640
Author(s):  
Geng Wang ◽  
Qingbo Wang ◽  
Jie Bai ◽  
Gang Li ◽  
Kaixiong Tao ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Portal Vein ◽  
Liver Lipid ◽  
Negative Control ◽  
Enzyme Linked Immunosorbent Assay ◽  
Induction Effect ◽  
Nonalcoholic Fatty Liver ◽  
Post Surgery

Background Roux-en-Y gastric bypass (RYGB) could reduce nonalcoholic fatty liver disease (NAFLD) ahead of the weight-loss effects. But the detailed mechanisms remain unclear. Material and methods A high-fat diet (HFD) was fed to induce obesity. RYGB was then performed. Gastric nesfatin-1 was measured by enzyme-linked immunosorbent assay (ELISA) in portal vein and polymerase chain reaction (PCR) in gastric tissues. Modified surgeries including vagus-preserved bypass and vagectomy were performed and postprandial gastric nesfatin-1 were analyzed. The effects of nesfatin-1 on hepatocytes were studied by PCR and immunohistochemistry. Both intraperitoneal and intracerebroventricular injection (ICV) were performed to analyze the in vivo effects on liver lipid metabolism. Results Increased postprandial portal vein nesfatin-1 was observed in RYGB but not in control groups. This increase is mainly due to induction of gastric nesfatin-1. A modified RYGB in which the gastric vagus is preserved is conducted and, in this case, this nesfatin-1 induction effect is diminished. Mere vagectomy could also induce a similar nesfatin-1 increase pattern. The infusion of nesfatin-1 in the brain could inhibit the expression of gastric nesfatin-1, and the effects are diminished after gastric vagectomy. In vivo and in vitro nesfatin-1 stimulation in the liver resulted in improvements in lipid metabolism. Conclusions Severing the gastric vagus during RYGB could cut off the negative control from the central nervous system (CNS) and result in increased postprandial gastric nesfatin-1 post surgery, which in turn, improves NAFLD.

scholarly journals MicroRNAs as a Novel Tool in the Diagnosis of Liver Lipid Dysregulation and Fatty Liver Disease

Molecules ◽  
2019 ◽  
Vol 24 (2) ◽  
pp. 230 ◽  
Author(s):  
Jingwei Yu ◽  
Jun Peng ◽  
Zhilin Luan ◽  
Feng Zheng ◽  
Wen Su
Keyword(s):  
Lipid Metabolism ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Metabolic Diseases ◽  
Liver Lipid ◽  
Biological Research ◽  
Regulation Mechanism ◽  
Hepatic Lipid Accumulation ◽  
Liver Lipid Metabolism

In recent years, metabolic disorder, especially fatty liver disease, has been considered a major challenge to global health. The attention of researchers focused on expanding knowledge of the regulation mechanism behind these diseases and towards the new diagnostics tools and treatments. The pathophysiology of the fatty liver disease is undoubtedly complex. Abnormal hepatic lipid accumulation is a major symptom of most metabolic diseases. Therefore, the identification of novel regulation factors of lipid metabolism is important and meaningful. As a new diagnostic tool, the function of microRNAs during fatty liver disease has recently come into notice in biological research. Accumulating evidence supports the influence of miRNAs in lipid metabolism. In this review, we discuss the potential role of miRNAs in liver lipid metabolism and the pathogenesis of fatty liver disease.

Fetuin A in nonalcoholic fatty liver disease: in vivo and in vitro studies

2012 ◽  
Vol 166 (3) ◽  
pp. 503-510 ◽  
Author(s):  
John Willy Haukeland ◽  
Tuva B Dahl ◽  
Arne Yndestad ◽  
Ivar P Gladhaug ◽  
Else Marit Løberg ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Liver Disease ◽  
Fatty Liver Disease ◽  
Mrna Levels ◽  
Fetuin A ◽  
Nonalcoholic Fatty Liver ◽  
Key Enzymes ◽  
Glucose And Lipid Metabolism

ObjectiveFetuin A has been associated with insulin resistance and the metabolic syndrome. We therefore explored the role of fetuin A in nonalcoholic fatty liver disease (NAFLD).DesignCross-sectional and intervention studies.MethodsWe included 111 subjects with histologically proven NAFLD of whom 44 participated in a randomized, controlled trial with metformin. One hundred and thirty-one healthy subjects and 13 subjects undergoing hepatic surgery for metastatic cancer served as controls. Main outcome variables were circulating levels of fetuin A according to the presence of NAFLD, hepatic gene expression of fetuin A and key enzymes in glucose and lipid metabolism, and the effect of metformin on fetuin A levels in vivo and in vitro (HepG2 cells).ResultsFetuin A levels were significantly higher in NAFLD patients compared with controls (324±98 vs 225±75 mg/l, P<0.001). NAFLD was a significant predictor of elevated fetuin A levels (β=174 (95% confidence interval: 110–234)) independent of body mass index, age, sex, fasting glucose, and triglycerides. Hepatic fetuin A mRNA levels correlated significantly with hepatic mRNA levels of key enzymes in lipid (sterol regulatory element-binding protein 1c, carnitine palmitoyltransferase 1) and glucose (phosphoenol pyruvate kinase 1, glucose-6-phosphatase) metabolism. Plasma fetuin A levels decreased significantly after metformin treatment compared with placebo (−40±47 vs 15±82 mg/l, P=0.008). Metformin induced a dose-dependent decrease in fetuin A secretion in vitro.ConclusionsFetuin A levels were elevated in NAFLD. Hepatic expression of fetuin A correlated with key enzymes in glucose and lipid metabolism. Metformin decreased fetuin A levels in vitro.

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