scholarly journals Activation of the Peroxisome Proliferator-Activated Receptors (PPAR-α/γ) and the Fatty Acid Metabolizing Enzyme Protein CPT1A by Camel Milk Treatment Counteracts the High-Fat Diet-Induced Nonalcoholic Fatty Liver Disease

PPAR Research ◽  
2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Haifa M. AlNafea ◽  
Aida A. Korish
Keyword(s):  
Liver Disease ◽  
Fatty Liver Disease ◽  
Fat Metabolism ◽  
Camel Milk ◽  
Peroxisome Proliferator ◽  
Protective Effects ◽  
High Fat ◽  
Nonalcoholic Fatty Liver ◽  
Tnf Α ◽  
Milk Treatment

Camel milk (CM) has a unique composition rich in antioxidants, trace elements, immunoglobulins, insulin, and insulin-like proteins. Treatment by CM demonstrated protective effects against nonalcoholic fatty liver disease (NAFLD) induced by a high-fat cholesterol-rich diet (HFD-C) in rats. CM dampened the steatosis, inflammation, and ballooning degeneration of the hepatocytes. It also counteracted hyperlipidemia, insulin resistance (IR), glucose intolerance, and oxidative stress. The commencement of NAFLD triggered the peroxisome proliferator-activated receptor-α (PPAR-α), carnitine palmitoyl-transferase-1 (CPT1A), and fatty acid-binding protein-1 (FABP1) and decreased the PPAR-γ expression in the tissues of the animals on HFD-C. This was associated with increased levels of the inflammatory cytokines IL-6 and TNF-α and leptin and declined levels of the anti-inflammatory adiponectin. Camel milk treatment to the NAFLD animals remarkably upregulated PPARs (α, γ) and the downstream enzyme CPT1A in the metabolically active tissues involved in cellular uptake and beta-oxidation of fatty acids. The enhanced lipid metabolism in the CM-treated animals was linked with decreased expression of FABP1 and suppression of IL-6, TNF-α, and leptin release with augmented adiponectin production. The protective effects of CM against the histological and biochemical features of NAFLD are at least in part related to the activation of the hepatic and extrahepatic PPARs (α, γ) with consequent activation of the downstream enzymes involved in fat metabolism. Camel milk treatment carries a promising therapeutic potential to NAFLD through stimulating PPARs actions on fat metabolism and glucose homeostasis. This can protect against hepatic steatosis, IR, and diabetes mellitus in high-risk obese patients.

scholarly journals Sijunzi, Lizhong, and Fuzilizhong Decoction Alleviate Nonalcoholic Fatty Liver Disease through Activation of PPAR Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Jiayao Yang ◽  
Dongqing Tao ◽  
Wei Ma ◽  
Song Liu ◽  
Yan Liao ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
High Fat Diet ◽  
Fatty Liver Disease ◽  
Molecular Mechanisms ◽  
Peroxisome Proliferator ◽  
High Fat ◽  
Peroxisome Proliferator Activated Receptor ◽  
Nonalcoholic Fatty Liver ◽  
Chinese Herbal

Objective. Sijunzi, Lizhong, and Fuzilizhong decoction were traditional Chinese classic formulations, which are widely used in clinical treatment, and the underlying mechanism is unclear. In this study, we aim to investigate the molecular mechanisms underlying the protective effects of Sijunzi, Lizhong, and Fuzilizhong on nonalcoholic fatty liver disease (NAFLD). Methods. Male Wistar rats were fed a high-fat diet for four weeks to induce NAFLD and were thereafter administered Sijunzi (8 g/kg/d), Lizhong (10 g/kg/d), or Fuzilizhong (10 g/kg/d) by gavage for four weeks. Hepatic damage, lipid accumulation, inflammation, autophagy, and peroxisome proliferator-activated receptor-α signaling were evaluated. Results. The high-fat diet-fed rats showed typical symptoms of NAFLD, including elevated levels of hepatic damage indicators, increased hepatic lipid deposition and fibrosis, severe liver inflammation, and prominent autophagy. Upon administration of Sijunzi, Lizhong, and Fuzilizhong, liver health was improved remarkably, along with ameliorated symptoms of NAFLD. In addition, NAFLD-suppressed peroxisome proliferator-activated receptor-α signaling was reactivated after treatment with the three types of decoctions. Conclusions. The results collectively signify the effective therapeutic and protective functions of Sijunzi, Lizhong, and Fuzilizhong against NAFLD and demonstrate the potential of Chinese herbal medication in mitigating the symptoms of liver diseases. Novelty of the Work. Traditional Chinese herbal medicine has been used for centuries to treat various diseases, but the molecular mechanisms of individual ingredients have rarely been studied. The novelty of our work lies in elucidating the specific signaling pathways involved in the control of NAFLD using three common Chinese herbal decoctions. We suggest that natural herbal formulations can be effective therapeutic agents to combat against NAFLD.

Activated TNF-α/RIPK3 signaling is involved in prolonged high fat diet-stimulated hepatic inflammation and lipid accumulation: inhibition by dietary fisetin intervention

2019 ◽  
Vol 10 (3) ◽  
pp. 1302-1316 ◽  
Author(s):  
Minxuan Xu ◽  
Chenxu Ge ◽  
Yuting Qin ◽  
Tingting Gu ◽  
Jinxiao Lv ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Liver Disease ◽  
Lipid Accumulation ◽  
High Fat Diet ◽  
Fatty Liver Disease ◽  
Hepatic Inflammation ◽  
High Fat ◽  
Predisposing Factor ◽  
Nonalcoholic Fatty Liver ◽  
Tnf Α

Increasing evidence indicates that high-fat diet (HFD) is a predisposing factor for metabolic syndrome-associated systemic inflammation and nonalcoholic fatty liver disease (NAFLD).

scholarly journals Lentinan Protects against Nonalcoholic Fatty Liver Disease by Reducing Oxidative Stress and Apoptosis via the PPARα Pathway

Metabolites ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 55
Author(s):  
Tingyi Du ◽  
Qin Fang ◽  
Zhihao Zhang ◽  
Chuanmeng Zhu ◽  
Renfan Xu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
High Fat Diet ◽  
Fatty Liver Disease ◽  
Chow Diet ◽  
Protective Effects ◽  
High Fat ◽  
Nonalcoholic Fatty Liver

Aim: Lentinan (LNT), a type of polysaccharide derived from Lentinus edodes, has manifested protective effects during liver injury and hepatocellular carcinoma, but little is known about its effects on nonalcoholic fatty liver disease (NAFLD). This study aimed to investigate whether LNT can affect the progression of NAFLD and the associated mechanisms. Methods: C57BL/6J mice were fed a normal chow diet or a high-fat diet (HFD) with or without LNT (6 mg/kg/d). AML12 cells were exposed to 200 μM palmitate acid (PA) with or without LNT (5 μg/mL). Results: After 21 wk of the high-fat diet, LNT significantly decreased plasma triglyceride levels and liver lipid accumulation, reduced excessive reactive oxygen species production, and subsequently attenuated hepatic apoptosis in NAFLD mice. These effects were associated with increased PPARα levels, a decreased Bax/Bcl-2 ratio, and enhancement of the antioxidant defense system in vivo. Similar effects were also observed in cultured cells. More importantly, these protective effects of LNT on palmitate acid-treated AML12 cells were almost abolished by PPARα knockdown. Conclusion: In conclusion, this study demonstrates that LNT may ameliorate hepatic steatosis and decrease oxidative stress and apoptosis by activating the PPARα pathway and is a potential drug target for NAFLD.

Hepatoprotective Activities of Polysaccharide From the Fruit of Ribes odoratum Wendl. on High-Fat-Sucrose Diet-Induced Nonalcoholic Fatty Liver Disease in Mice

2020 ◽  
Vol 15 (8) ◽  
pp. 1934578X2094693
Author(s):  
Lin-you Zou ◽  
Na Hu ◽  
Ning Wang ◽  
Hong-lun Wang
Keyword(s):  
Liver Disease ◽  
Liver Fibrosis ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Control Group ◽  
Model Group ◽  
High Fat ◽  
Nonalcoholic Fatty Liver ◽  
Tnf Α ◽  
Sucrose Diet

To investigate the hepatoprotective activities of a polysaccharide extracted from the fruit of Ribes odoratum Wendl. (ROWFP) in a mouse model of high-fat-sucrose diet (HFD)-induced nonalcoholic fatty liver disease (NAFLD). The NAFLD model was induced in C57BL/6 mice by feeding them an HFD for 12 weeks. The mice were randomly divided into the following 5 groups: control group, HFD group, 10-mg/kg ROWFP group, 100-mg/kg ROWFP group, and 200-mg/kg ROWFP group. The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total triglycerides (TG), total cholesterol (TC), and high-density lipoprotein (HDL) in the serum were analyzed by enzyme-linked immunosorbent assay. The liver ultrastructure was observed via optical microscopy. The oil red O-stained lipid droplets of the fresh liver samples were analyzed, and the lipid content was semiquantified. CD68 expression in the liver tissue and serum levels of the inflammatory factors (interleukin [IL]-1β, IL-6, and tumor necrosis factor-alpha [TNF-α]) were measured to reflect the inflammation status. The degree of liver fibrosis was determined by sirius red staining. When compared with the control group, the levels of AST, ALT, TG, TC, IL-1β, IL-6, TNF-α, and CD68 in the HFD group were increased, while the HDL level was decreased. Severe liver damage, lipid accumulation, and liver fibrosis were also observed in the HFD model group. When compared with the model group, ROWFP treatment (100 mg/kg or 200 mg/kg) significantly attenuated the HFD-induced hepatic damage. This study supports the hepatoprotective effect of ROWFP against HFD-induced NAFLD.

scholarly journals Elucidation of SIRT-1/PGC-1α-associated mitochondrial dysfunction and autophagy in nonalcoholic fatty liver disease

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Yan Jiang ◽  
Duankai Chen ◽  
Qiming Gong ◽  
Qunqing Xu ◽  
Dong Pan ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Sirtuin 1 ◽  
Liver Fat ◽  
Peroxisome Proliferator ◽  
High Fat ◽  
Peroxisome Proliferator Activated Receptor ◽  
Nonalcoholic Fatty Liver

Abstract Background Nonalcoholic fatty liver disease (NAFLD) can lead to chronic liver diseases associated with mitochondrial damages. However, the exact mechanisms involved in the etiology of the disease are not clear. Methods To gain new insights, the changes affecting sirtuin 1 (SIRT-1) during liver fat accumulation was investigated in a NAFLD mouse model. In addition, the in vitro research investigated the regulation operated by SIRT-1 on mitochondrial structures, biogenesis, functions, and autophagy. Results In mice NAFLD, high-fat-diet (HFD) increased body weight gain, upregulated serum total cholesterol, triglycerides, aspartate aminotransferase, alanine aminotransferase, blood glucose, insulin levels, and liver malondialdehyde, and decreased liver superoxide dismutase activity. In liver, the levels of SIRT-1 and peroxisome proliferator-activated receptor-gamma coactivator -1α (PGC-1α) decreased. The expression of peroxisome proliferator-activated receptor-α and Beclin-1 proteins was also reduced, while p62/SQSTM1 expression increased. These results demonstrated SIRT-1 impairment in mouse NAFLD. In a well-established NAFLD cell model, exposure of the HepG2 hepatocyte cell line to oleic acid (OA) for 48 h caused viability reduction, apoptosis, lipid accumulation, and reactive oxygen species production. Disturbance of SIRT-1 expression affected mitochondria. Pre-treatment with Tenovin-6, a SIRT-1 inhibitor, aggravated the effect of OA on hepG2, while this effect was reversed by CAY10602, a SIRT-1 activator. Further investigation demonstrated that SIRT-1 activity was involved in mitochondrial biogenesis through PGC-1α and participated to the balance of autophagy regulatory proteins. Conclusion In conclusion, in high-fat conditions, SIRT-1 regulates multiple cellular properties by influencing on mitochondrial physiology and lipid autophagy via the PGC-1α pathway. The SIRT-1/PGC-1α pathway could be targeted to develop new NAFLD therapeutic strategies.

scholarly journals Astragaloside IV Improves High-Fat Diet–Induced Hepatic Steatosis in Nonalcoholic Fatty Liver Disease Rats by Regulating Inflammatory Factors Level via TLR4/NF-κB Signaling Pathway

2021 ◽  
Vol 11 ◽  
Author(s):  
Ying-Li Liu ◽  
Qiu-Zan Zhang ◽  
Yan-Rong Wang ◽  
Li-Na Fu ◽  
Jing-Shu Han ◽  
...  
Keyword(s):  
Liver Disease ◽  
Normal Saline ◽  
High Fat Diet ◽  
Fatty Liver Disease ◽  
Intragastric Administration ◽  
Astragaloside Iv ◽  
High Fat ◽  
Nonalcoholic Fatty Liver ◽  
Tnf Α ◽  
Nafld Activity Score

Objective: Astragaloside IV (AS-IV) is the primary bioactive component purified from Astragalus membranaceus which is one of the traditional Chinese medicines. Research studies found that AS-IV has significant pharmacological effects on focal cerebral ischemia/reperfusion, cardiovascular disease, pulmonary disease, liver cirrhosis, and diabetic nephropathy, but little is known about the effects of AS-IV on nonalcoholic fatty liver disease (NAFLD). In this study, we investigated whether AS-IV has beneficial effects on NAFLD in rats and its potential mechanisms.Methods: Male SD rats were fed with high-fat diet (HFD) for 12 weeks to establish NAFLD rat model, and then, the rats were divided into five groups. The control group rats were fed with normal diet for 12 weeks and then were given normal saline (1.0 ml kg−1 day−1) by intragastric administration for 4 weeks. The model group rats were fed with HFD for 12 weeks and then were given normal saline (1.0 ml kg−1 day−1) by intragastric administration for 4 weeks. The AS-IV-L, AS-IV-M, and AS-IV-H groups were treated with 20, 40, and 80 mg kg−1 day−1 of AS-IV by intragastric administration for 4 weeks and given HFD diet. Then, we detected serum transaminase (ALT, AST), blood lipid (TG, TC), inflammatory cytokines (IL-6, IL-8 and TNF-α), liver histology(NAFLD activity score), TLR4/MyD88 signaling pathway in liver tissue.Results: We found AS-IV significantly reduced serum levels of AST, ALT, TG, TNF-α, IL-6, and IL-8 in NAFLD rats and downregulate the expression of TLR4 mRNA, MyD88 mRNA, NF-κB mRNA, and proteins in liver tissue. Moreover, AS-IV could significantly reduce the NAFLD activity score of NAFLD rat liver.Conclusion: In this study, we demonstrated that AS-IV have a protective effect on NAFLD by inhibiting TNF-α, IL-6 and IL-8 levels and down-regulating TLR4, MyD88 and NF-κB expression in rat liver tissues.

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