scholarly journals Cynanchum atratum Alleviates Non-Alcoholic Fatty Liver by Balancing Lipogenesis and Fatty Acid Oxidation in a High-Fat, High-Fructose Diet Mice Model

Cells ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 23
Author(s):  
Jing-Hua Wang ◽  
Seung-Ju Hwang ◽  
Dong-Woo Lim ◽  
Chang-Gue Son
Keyword(s):  
Fatty Acid ◽  
Fatty Liver ◽  
Fatty Acid Oxidation ◽  
The Body ◽  
Acid Oxidation ◽  
High Fat ◽  
Alcoholic Fatty Liver ◽  
High Fructose Diet ◽  
High Fructose ◽  
Tnf Α

Cynanchum atratum, a medicinal herb, is traditionally used as an antidote, diuretic, and antipyretic in eastern Asia. The current study aimed to investigate the anti-fatty liver capacity of the ethanol extract of Cynanchum atratum (CAE) using a 10-week high-fat, high-fructose diet mouse model. A six-week treatment of CAE (from the fifth week) significantly attenuated the weights of the body, liver, and mesenteric fat without a change in diet intake. CAE also considerably restored the alterations of serum aminotransferases and free fatty acid, fasting blood glucose, serum and hepatic triglyceride, and total cholesterol, as well as platelet and leukocyte counts. Meanwhile, CAE ameliorated hepatic injury and lipid accumulation, as evidenced by histopathological and immunofluorescence observations. Additionally, CAE significantly lowered the elevation of hepatic TNF-α, the TNF-α/IL-10 ratio, fecal endotoxins, and the abundance of Gram-negative bacteria. Hepatic lipogenesis and β-oxidation-related proteins and gene expression, including PPAR-α, SREBP-1, SIRT1, FAS, CTP1, etc., were normalized markedly by CAE. In particular, the AMPK, a central regulator of energy metabolism, was phosphorylated by CAE at an even higher rate than metformin. Overall, CAE exerts anti-hepatic steatosis effects by reducing lipogenesis and enhancing fatty acid oxidation. Consequently, Cynanchum atratum is expected to be a promising candidate for treating chronic metabolic diseases.

scholarly journals Antrodan Alleviates High-Fat and High-Fructose Diet-Induced Fatty Liver Disease in C57BL/6 Mice Model via AMPK/Sirt1/SREBP-1c/PPARγ Pathway

2020 ◽  
Vol 21 (1) ◽  
pp. 360 ◽  
Author(s):  
Charng-Cherng Chyau ◽  
Hsueh-Fang Wang ◽  
Wen-Juan Zhang ◽  
Chin-Chu Chen ◽  
Shiau-Huei Huang ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Mice Model ◽  
High Fat ◽  
Alcoholic Fatty Liver ◽  
High Fructose Diet ◽  
High Fructose ◽  
Ant Control ◽  
Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) and -steatohepatitis (NASH) imply a state of excessive fat built-up in livers with/or without inflammation and have led to serious medical concerns in recent years. Antrodan (Ant), a purified β-glucan from A. cinnamomea has been shown to exhibit tremendous bioactivity, including hepatoprotective, antihyperlipidemic, antiliver cancer, and anti-inflammatory effects. Considering the already well-known alleviating bioactivity of A. cinnamomea for the alcoholic steatohepatitis (ASH), we propose that Ant can be beneficial to NAFLD, and that the AMPK/Sirt1/PPARγ/SREBP-1c pathways may be involved in such alleviations. To uncover this, we carried out this study with 60 male C57BL/6 mice fed high-fat high-fructose diet (HFD) for 60 days, in order to induce NAFLD/NASH. Mice were then grouped and treated (by oral administration) as: G1: control; G2: HFD (HFD control); G3: Ant, 40 mgkg (Ant control); G4: HFD+Orlistat (10 mg/kg) (as Orlistat control); G5: HFD+Ant L (20 mg/kg); and G6: HFD+Ant H (40 mg/kg) for 45 days. The results indicated Ant at 40 mg/kg effectively suppressed the plasma levels of malondialdehyde, total cholesterol, triglycerides, GOT, GPT, uric acid, glucose, and insulin; upregulated leptin, adiponectin, pAMPK, Sirt1, and down-regulated PPARγ and SREBP-1c. Conclusively, Ant effectively alleviates NAFLD via AMPK/Sirt1/CREBP-1c/PPARγ pathway.

scholarly journals Involvement of adiponectin-SIRT1-AMPK signaling in the protective action of rosiglitazone against alcoholic fatty liver in mice

2010 ◽  
Vol 298 (3) ◽  
pp. G364-G374 ◽  
Author(s):  
Zheng Shen ◽  
Xiaomei Liang ◽  
Christopher Q. Rogers ◽  
Drew Rideout ◽  
Min You
Keyword(s):  
Fatty Acid ◽  
Fatty Liver ◽  
Fatty Acid Oxidation ◽  
Protective Action ◽  
Sirtuin 1 ◽  
Acid Oxidation ◽  
Adiponectin Receptors ◽  
Alcoholic Fatty Liver ◽  
Ampk Signaling ◽  
Ppar Γ

The development of alcoholic fatty liver is associated with reduced adipocyte-derived adiponectin levels, decreased hepatic adiponectin receptors, and deranged hepatic adiponectin signaling in animals. Peroxisomal proliferator-activated receptor-γ (PPAR-γ) plays a key role in the regulation of adiponectin in adipose tissue. The aim of the present study was to test the ability of rosiglitazone, a known PPAR-γ agonist, to reverse the inhibitory effects of ethanol on adiponectin expression and its hepatic signaling, and to attenuate alcoholic liver steatosis in mice. Mice were fed modified Lieber-DeCarli ethanol-containing liquid diets for 4 wk or pair-fed control diets. Four groups of mice were given a dose of either 3 or 10 mg·kg body wt−1·day−1 of rosiglitazone with or without ethanol in their diets for the last 2 wk of the feeding study. Coadministration of rosiglitazone and ethanol increased the expression and circulating levels of adiponectin and enhanced the expression of hepatic adiponectin receptors (AdipoRs) in mice. These increases correlated closely with the activation of a hepatic sirtuin 1 (SIRT1)-AMP-activated kinase (AMPK) signaling system. In concordance with stimulated SIRT1-AMPK signaling, rosiglitazone administration enhanced expression of fatty acid oxidation enzymes, normalized lipin 1 expression, and blocked elevated expression of genes encoding lipogenic enzymes which, in turn, led to increased fatty acid oxidation, reduced lipogenesis, and alleviation of steatosis in the livers of ethanol-fed mice. Enhanced hepatic adiponectin-SIRT1-AMPK signaling contributes, at least in part, to the protective action of rosiglitazone against alcoholic fatty liver in mice.

scholarly journals Aurantio-Obtusin Attenuates Non-Alcoholic Fatty Liver Disease Through AMPK-Mediated Autophagy and Fatty Acid Oxidation Pathways

2022 ◽  
Vol 12 ◽  
Author(s):  
Fei Zhou ◽  
Mingning Ding ◽  
Yiqing Gu ◽  
Guifang Fan ◽  
Chuanyang Liu ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Liver Disease ◽  
Fatty Liver ◽  
Hepatic Steatosis ◽  
Fatty Acid Oxidation ◽  
Lipid Accumulation ◽  
Fatty Liver Disease ◽  
Acid Oxidation ◽  
Alcoholic Fatty Liver ◽  
Nonalcoholic Fatty Liver

Nonalcoholic fatty liver disease (NAFLD), manifested as the aberrant accumulation of lipids in hepatocytes and inflammation, has become an important cause of advanced liver diseases and hepatic malignancies worldwide. However, no effective therapy has been approved yet. Aurantio-obtusin (AO) is a main bioactive compound isolated from Cassia semen that has been identified with multiple pharmacological activities, including improving adiposity and insulin resistance. However, the ameliorating effects of AO on diet-induced NAFLD and underlying mechanisms remained poorly elucidated. Our results demonstrated that AO significantly alleviated high-fat diet and glucose-fructose water (HFSW)-induced hepatic steatosis in mice and oleic acid and palmitic acid (OAPA)-induced lipid accumulation in hepatocytes. Remarkably, AO was found to distinctly promote autophagy flux and influence the degradation of lipid droplets by inducing AMPK phosphorylation. Additionally, the induction of AMPK triggered TFEB activation and promoted fatty acid oxidation (FAO) by activating PPARα and ACOX1 and decreasing the expression of genes involved in lipid biosynthesis. Meanwhile, the lipid-lowing effect of AO was significantly prevented by the pretreatment with inhibitors of autophagy, PPARα or ACOX1, respectively. Collectively, our study suggests that AO ameliorates hepatic steatosis via AMPK/autophagy- and AMPK/TFEB-mediated suppression of lipid accumulation, which opens new opportunities for pharmacological treatment of NAFLD and associated complications.

scholarly journals Germinated Soybean Embryo Extract Ameliorates Fatty Liver Injury in High-Fat Diet-Fed Obese Mice

2020 ◽  
Vol 13 (11) ◽  
pp. 380
Author(s):  
Doyoung Kwon ◽  
Sou Hyun Kim ◽  
Seung Won Son ◽  
Jinuk Seo ◽  
Tae Bin Jeong ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Fatty Liver ◽  
High Fat Diet ◽  
Ethanolic Extract ◽  
The Body ◽  
Acid Oxidation ◽  
High Fat ◽  
Alcoholic Fatty Liver ◽  
Triglyceride Accumulation ◽  
Germinated Soybean

Soybean is known to have diverse beneficial effects against human diseases, including obesity and its related metabolic disorders. Germinated soybean embryos are enriched with bioactive phytochemicals and known to inhibit diet-induced obesity in mice, but their effect on non-alcoholic fatty liver disease (NAFLD) remains unknown. Here, we germinated soybean embryos for 24 h, and their ethanolic extract (GSEE, 15 and 45 mg/kg) was administered daily to mice fed with a high-fat diet (HFD) for 10 weeks. HFD significantly increased the weight of the body, liver and adipose tissue, as well as serum lipid markers, but soyasaponin Ab-rich GSEE alleviated these changes. Hepatic injury and triglyceride accumulation in HFD-fed mice were attenuated by GSEE via decreased lipid synthesis (SREBP1c) and increased fatty acid oxidation (p-AMPKα, PPARα, PGC1α, and ACOX) and lipid export (MTTP and ApoB). HFD-induced inflammation (TNF-α, IL-6, IL-1β, CD14, F4/80, iNOS, and COX2) was normalized by GSEE in mice livers. In adipose tissue, GSEE downregulated white adipose tissue (WAT) differentiation and lipogenesis (PPARγ, C/EBPα, and FAS) and induced browning genes (PGC1α, PRDM16, CIDEA, and UCP1), which could also beneficially affect the liver via lowering adipose tissue-related circulating lipid levels. Thus, our results suggest that GSEE can prevent HFD-induced NAFLD via inhibition of hepatic inflammation and restoration of lipid metabolisms in both liver and adipose tissue.

scholarly journals Dietary fatty acid oxidation is decreased in non‐alcoholic fatty liver disease: A palmitate breath test study

2019 ◽  
Vol 40 (3) ◽  
pp. 590-597 ◽  
Author(s):  
Gihan Naguib ◽  
Nevitt Morris ◽  
Shanna Yang ◽  
Nancy Fryzek ◽  
Vanessa Haynes‐Williams ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Acid Oxidation ◽  
Fatty Liver Disease ◽  
Breath Test ◽  
Acid Oxidation ◽  
Alcoholic Fatty Liver ◽  
Test Study ◽  
Alcoholic Fatty Liver Disease

scholarly journals Quercetin Ameliorates Fatty Acid Oxidation in the Pathogenesis of NAFLD Based on Network Pharmacology and Molecular Docking

2021 ◽  
Author(s):  
Wenyu Zhu ◽  
Yufan Dai ◽  
Jingjing Lin ◽  
Yanhong Chen ◽  
Xiangshu Rao ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Fatty Acid ◽  
Liver Disease ◽  
Fatty Acid Oxidation ◽  
High Fat Diet ◽  
Network Pharmacology ◽  
Acid Oxidation ◽  
High Fat ◽  
Alcoholic Fatty Liver ◽  
Glutamyl Transferase

Abstract The high-fat diet (HFD) has dramatically increased the prevalence of non-alcoholic fatty liver disease (NAFLD), such that it is the leading cause of chronic liver disease worldwide. With novel knowledge on pathogenesis of NAFLD, we illustrated molecular targets for pharmacologic and experimental approaches. Our study showed that quercetin was the valuable drug candidate, and the core targets such as PPARα, MCAD, LCAD, CPT1-L, CPT2 and FATP2 which participate in fatty acid oxidation were selected to perform further in vivo experiments based on network pharmacology and molecular docking technology. The effect was investigated in a high-fat diet-induced NAFLD male Sprague Dawley rat model by hepatic biochemical assays. Serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and γ-glutamyl transferase analyses assessed liver function. Liver tissues were collected for histological staining, quantitative real-time PCR and western blotting. Greatly, quercetin reduced hepatic lipid accumulation and inflammation, ameliorated pathological liver changes, and up-regulated the expression levels of hepatic effectors in fatty acid oxidation. The results suggest the potential of quercetin as a nutritional supplement to HFD-induced NAFLD. Furthermore, the antagonist and agonist of PPARα provided a reliable scientific basis that these above-mentioned effectors were activated by quercetin via the PPAR pathway.

scholarly journals Ahnak deficiency attenuates high-fat diet-induced fatty liver in mice through FGF21 induction

2021 ◽  
Author(s):  
Yo Na Kim ◽  
Jae Hoon Shin ◽  
Dong Soo Kyeong ◽  
Soo Young Cho ◽  
Mi-Young Kim ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Lipid Metabolism ◽  
Fatty Liver ◽  
Hepatic Steatosis ◽  
Fatty Acid Oxidation ◽  
High Fat Diet ◽  
Fibroblast Growth Factor 21 ◽  
Acid Oxidation ◽  
Chow Diet ◽  
High Fat

AbstractThe AHNAK nucleoprotein has been determined to exert an anti-obesity effect in adipose tissue and further inhibit adipogenic differentiation. In this study, we examined the role of AHNAK in regulating hepatic lipid metabolism to prevent diet-induced fatty liver. Ahnak KO mice have reportedly exhibited reduced fat accumulation in the liver and decreased serum triglyceride (TG) levels when provided with either a normal chow diet or a high-fat diet (HFD). Gene expression profiling was used to identify novel factors that could be modulated by genetic manipulation of the Ahnak gene. The results revealed that fibroblast growth factor 21 (FGF21) was markedly increased in the livers of Ahnak KO mice compared with WT mice fed a HFD. Ahnak knockdown in hepatocytes reportedly prevented excessive lipid accumulation induced by palmitate treatment and was associated with increased secretion of FGF21 and the expression of genes involved in fatty acid oxidation, which are primarily downstream of PPARα. These results indicate that pronounced obesity and hepatic steatosis are attenuated in HFD-fed Ahnak KO mice. This may be attributed, in part, to the induction of FGF21 and regulation of lipid metabolism, which are considered to be involved in increased fatty acid oxidation and reduced lipogenesis in the liver. These findings suggest that targeting AHNAK may have beneficial implications in preventing or treating hepatic steatosis.

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