Dietary raffinose ameliorates hepatic lipid accumulation induced by cholic acid via modulation of enterohepatic bile acid circulation in rats

2021 ◽  
pp. 1-26
Author(s):  
Kenta Maegawa ◽  
Haruka Koyama ◽  
Satoru Fukiya ◽  
Atsushi Yokota ◽  
Koichiro Ueda ◽  
...  
Keyword(s):  
Acetic Acid ◽  
Bile Acid ◽  
Cholic Acid ◽  
Lipid Accumulation ◽  
Enterohepatic Circulation ◽  
Control Diet ◽  
Hepatic Triglyceride ◽  
Alcoholic Fatty Liver ◽  
Hepatic Lipid ◽  
Hepatic Lipid Accumulation

Abstract Enterohepatic circulation of 12α-hydroxylated (12αOH) bile acid (BA) is enhanced depending on the energy intake in high-fat diet-fed rats. Such BA metabolism can be reproduced using a diet supplemented with cholic acid (CA), which also induces simple steatosis, without inflammation and fibrosis, accompanied by some other symptoms that are frequently observed in the condition of non-alcoholic fatty liver in rats. We investigated whether supplementation of the diet with raffinose (Raf) improves hepatic lipid accumulation induced by the CA-fed condition in rats. After acclimation to the AIN-93-based control diet, male Wistar rats were fed diets supplemented with a combination of Raf (30 g/kg diet) and/or CA (0.5 g/kg diet) for 4 weeks. Dietary Raf normalised hepatic triglyceride levels (two-way ANOVA P<0.001 for CA, P=0.02 for Raf, and P=0.004 for interaction) in the CA-supplemented diet-fed rats. Dietary Raf supplementation reduced hepatic 12αOH BA concentration (two-way ANOVA P<0.001 for CA, P=0.003 for Raf, and P=0.03 for interaction). The concentration of 12αOH BA was reduced in the aortic and portal plasma. Raf supplementation increased acetic acid concentration in the caecal contents (two-way ANOVA P=0.001 as a main effect). Multiple regression analysis revealed that concentrations of aortic 12αOH BA and caecal acetic acid could serve as predictors of hepatic triglyceride concentration (R2=0.55, P<0.001). However, Raf did not decrease the secondary 12αOH BA concentration in the caecal contents as well as the transaminase activity in the CA diet-fed rats. These results imply that dietary Raf normalises hepatic lipid accumulation via suppression of enterohepatic 12αOH BA circulation.

scholarly journals N-Acetyl Cysteine Targets Hepatic Lipid Accumulation to Curb Oxidative Stress and Inflammation in NAFLD: A Comprehensive Analysis of the Literature

Antioxidants ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 1283
Author(s):  
Phiwayinkosi V. Dludla ◽  
Bongani B. Nkambule ◽  
Sithandiwe E. Mazibuko-Mbeje ◽  
Tawanda M. Nyambuya ◽  
Fabio Marcheggiani ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lipid Accumulation ◽  
Randomized Clinical Trials ◽  
Therapeutic Potential ◽  
Therapeutic Effects ◽  
Metabolic Complications ◽  
Alcoholic Fatty Liver ◽  
Hepatic Lipid ◽  
Hepatic Lipid Accumulation ◽  
Acetyl Cysteine

Impaired adipose tissue function and insulin resistance remain instrumental in promoting hepatic lipid accumulation in conditions of metabolic syndrome. In fact, enhanced lipid accumulation together with oxidative stress and an abnormal inflammatory response underpin the development and severity of non-alcoholic fatty liver disease (NAFLD). There are currently no specific protective drugs against NAFLD, and effective interventions involving regular exercise and healthy diets have proved difficult to achieve and maintain. Alternatively, due to its antioxidant and anti-inflammatory properties, there has been growing interest in understanding the therapeutic effects of N-acetyl cysteine (NAC) against metabolic complications, including NAFLD. Here, reviewed evidence suggests that NAC blocks hepatic lipid accumulation in preclinical models of NAFLD. This is in part through the effective regulation of a fatty acid scavenger molecule (CD36) and transcriptional factors such as sterol regulatory element-binding protein (SREBP)-1c/-2 and peroxisome proliferator-activated receptor gamma (PPARγ). Importantly, NAC appears effective in improving liver function by reducing pro-inflammatory markers such as interleukin (IL)-6 IL-1β, tumour necrosis factor alpha (TNF-α) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). This was primarily through the attenuation of lipid peroxidation and enhancements in intracellular response antioxidants, particularly glutathione. Very few clinical studies support the beneficial effects of NAC against NAFLD-related complications, thus well-organized randomized clinical trials are still necessary to confirm its therapeutic potential.

scholarly journals Jiao Tai Wan Attenuates Hepatic Lipid Accumulation in Type 2 Diabetes Mellitus

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Zhaoyi Huang ◽  
Xiaohu Xu ◽  
Fuer Lu ◽  
Nan Wang ◽  
Guang Chen ◽  
...  
Keyword(s):  
Lipid Accumulation ◽  
Diabetic Rats ◽  
Diabetic Patients ◽  
Hepatic Triglyceride ◽  
Hepatic Lipid ◽  
Hepatic Lipid Accumulation ◽  
Lipogenic Gene Expression ◽  
Protein Expressions ◽  
Triglyceride Content ◽  
Main Components

Jiao Tai Wan (JTW), a Chinese herbal formula containing Rhizoma Coptidis and Cortex Cinnamomi, has been used for diabetic treatment for many years. The aim of this study was to determine the main components in JTW and to investigate the effects of JTW on hepatic lipid accumulation in diabetic rats and humans. JTW extract was prepared and the main components were assayed by HPLC. An animal model of diabetes mellitus was established and JTW was administered intragastrically. In the clinical study, diabetic patients with poor glycemic control were treated with JTW. Blood glucose and lipid parameters, liver histology, hepatic triglyceride content and lipogenic gene expression were examined. Our data demonstrated that JTW significantly improved hyperglycemia, hyperlipidemia and hepatic lipid accumulation in diabetic rats. This was accompanied by the down-regulation of acetyl coenzyme A carboxylase (ACC) and fatty acid synthase (FAS) protein expressions, and the up-regulation of AMP-activated protein kinase (AMPK) and phosphorylated-ACC (pACC) protein expressions in the liver tissues. Diabetic patients also exhibited decreases in their hepatic triglyceride content. The results suggest that JTW attenuates hepatic lipid accumulation in diabetic rats and humans. These beneficial effects are possibly associated with the inhibition of lipogenic gene expression in the liver.

scholarly journals HFD-induced hepatic lipid accumulation and inflammation are decreased in Factor D deficient mouse

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Hiromi Tsuru ◽  
Mizuko Osaka ◽  
Yuichi Hiraoka ◽  
Masayuki Yoshida
Keyword(s):  
Lipid Accumulation ◽  
De Novo ◽  
Fatty Acid Uptake ◽  
De Novo Lipogenesis ◽  
Inflammatory Factors ◽  
Acid Uptake ◽  
Alcoholic Fatty Liver ◽  
Hepatic Lipid ◽  
Hepatic Lipid Accumulation ◽  
Expression Of Genes

Abstract Excessive intake of fat causes accumulation of fat in liver, leading to non-alcoholic fatty liver disease (NAFLD). High-fat diet (HFD) upregulates the expression of Factor D, a complement pathway component, in the liver of mice. However, the functions of Factor D in liver are not well known. Therefore, the current study investigated the relationship between Factor D and hepatic lipid accumulation using CRISPR/Cas9-mediated Factor D knockout (FD-KO) mice. Factor D deficiency downregulated expression of genes related to fatty acid uptake and de novo lipogenesis in the liver. Furthermore, Factor D deficiency reduced the expression of inflammatory factors (Tnf and Ccl2) and fibrosis markers and decreased accumulation of F4/80-positive macrophages. These data suggest that the Factor D deficiency improved hepatic lipid accumulation and hepatic inflammation in HFD-fed mice.

scholarly journals Sterol O-acyltransferase 2 chaperoned by apolipoprotein J facilitates hepatic lipid accumulation following viral and nutrient stresses

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Hung-Yu Sun ◽  
Tzu-Ying Chen ◽  
Yu-Ching Tan ◽  
Chun-Hsiang Wang ◽  
Kung-Chia Young
Keyword(s):  
Cholesteryl Ester ◽  
Lipid Accumulation ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Alcoholic Fatty Liver ◽  
Hepatic Lipid ◽  
Hepatic Lipid Accumulation ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Regions ◽  
Apolipoprotein J

AbstractThe risks of non-alcoholic fatty liver disease (NAFLD) include obese and non-obese stresses such as chronic hepatitis C virus (HCV) infection, but the regulatory determinants remain obscure. Apolipoprotein J (ApoJ) served as an ER-Golgi contact-site chaperone near lipid droplet (LD), facilitating HCV virion production. We hypothesized an interplay between hepatic ApoJ, cholesterol esterification and lipid deposit in response to NAFLD inducers. Exposures of HCV or free-fatty acids exhibited excess LDs along with increased ApoJ expression, whereas ApoJ silencing alleviated hepatic lipid accumulation. Both stresses could concomitantly disperse Golgi, induce closer ApoJ and sterol O-acyltransferase 2 (SOAT2) contacts via the N-terminal intrinsically disordered regions, and increase cholesteryl-ester. Furthermore, serum ApoJ correlated positively with cholesterol and low-density lipoprotein levels in normal glycaemic HCV patients, NAFLD patients and in mice with steatosis. Taken together, hepatic ApoJ might activate SOAT2 to supply cholesteryl-ester for lipid loads, thus providing a therapeutic target of stress-induced steatosis.

scholarly journals Urinary Medium-Chained Acyl-Carnitines Sign High Caloric Intake whereas Short-Chained Acyl-Carnitines Sign High -Protein Diet within a High-Fat, Hypercaloric Diet in a Randomized Crossover Design Dietary Trial

Nutrients ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 1191
Author(s):  
Nadezda V. Khodorova ◽  
Annemarie Rietman ◽  
Douglas N. Rutledge ◽  
Jessica Schwarz ◽  
Julien Piedcoq ◽  
...  
Keyword(s):  
Lipid Accumulation ◽  
Control Diet ◽  
Crossover Design ◽  
Short Chain ◽  
Control Group ◽  
High Fat ◽  
Hepatic Lipid ◽  
Hepatic Lipid Accumulation ◽  
Early Biomarkers ◽  
Hypercaloric Diet

The western dietary pattern is known for its frequent meals rich in saturated fat and protein, resulting in a postprandial state for a large part of the day. Therefore, our aim was to investigate the postprandial glucose and lipid metabolism in response to high (HP) or normal (NP) protein, high-fat hypercaloric diet and to identify early biomarkers of protein intake and hepatic lipid accumulation. In a crossover design, 17 healthy subjects were randomly assigned to consume a HP or NP hypercaloric diet for two weeks. In parallel, a control group (CD; n = 10) consumed a weight-maintaining control diet. Biomarkers of postprandial lipid and glucose metabolism were measured in 24 h urine and in plasma before and following a meal challenge. The metabolic profile of urine but not plasma, showed increased excretion of 13C, carnitine and short chain acyl-carnitines after adaptation to the HP diet. Urinary excretion of decatrienoylcarnitine and octenoylcarnitine increased after adaptation to the NP diet. Our results suggest that the higher excretion of short-chain urinary acyl-carnitines could facilitate the elimination of excess fat of the HP diet and thereby reduce hepatic fat accumulation previously reported, whereas the higher excretion medium-chains acyl-carnitine could be early biomarkers of hepatic lipid accumulation.

scholarly journals Apigenin Alleviates Non-Alcoholic Fatty Liver Disease by Downregulating the NLRP3/NF-κB Signaling Pathway in Mice

2021 ◽  
Author(s):  
Zheng Lu ◽  
Lu Liu ◽  
Shunxin Zhao ◽  
Jiangtao Zhao ◽  
Sujun Li
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Signaling Pathway ◽  
Lipid Accumulation ◽  
Hepg2 Cells ◽  
Fatty Liver Disease ◽  
Alcoholic Fatty Liver ◽  
Hepatic Lipid ◽  
Hepatic Lipid Accumulation

Abstract Background: Apigenin, a flavone found in several plant foods with various biological properties including anti-inflammatory and other abilities, alleviated non-alcohol fatty liver disease (NAFLD) induced by a high fat diet (HFD) in mice. However, the mechanisms underlying this protection of inflammation and NAFLD has not been known clearly. Methods: Low density lipoprotein receptor-deficient (Ldlr-/-) mice were fed with HFD diet to induce NAFLD model and were treated with apigenin (50 mg/kg/day) for eight weeks. Hepatic lipid accumulation and inflammation in the livers were analyzed and quantified. In vitro experiments, HepG2 cells were stimulated by LPS plus oleic acid (OA) in the absence of presence of apigenin (50μM). Lipid accumulation and the effect of apigenin on NLRP3/NF-κB signaling pathway was investigated.Results: Apigenin administration reduce the weight, plasma lipid levels in Ldlr-/- mice when fed an HFD. Apigenin (50 mg/kg/day) treated mice displayed reduced hepatic lipid accumulation and inflammation in the livers of mice given the HFD diet. Treating the HepG2 cells with apigenin reduced lipid accumulation. And, apigenin also inhibited activation of NLRP3/NF-κB signaling pathway stimulated by OA together with LPS. Conclusions: Our results indicated that apigenin supplementation prevented NAFLD via down-regulating the NLRP3/NF-κB signaling pathway in mice, and suggested apigenin might be a potential therapeutic agent for the prevention of NAFLD.

scholarly journals Lingonberry Improves Non-Alcoholic Fatty Liver Disease by Reducing Hepatic Lipid Accumulation, Oxidative Stress and Inflammatory Response

Antioxidants ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 565
Author(s):  
Susara Madduma Hewage ◽  
Suvira Prashar ◽  
Karmin O ◽  
Yaw L. Siow
Keyword(s):  
Oxidative Stress ◽  
Liver Disease ◽  
Liver Injury ◽  
Lipid Accumulation ◽  
Fatty Liver Disease ◽  
Inflammatory Cytokine ◽  
Alcoholic Fatty Liver ◽  
Hepatic Lipid ◽  
Hepatic Lipid Accumulation ◽  
Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease globally and there is a pressing need for effective treatment. Lipotoxicity and oxidative stress are the important mediators in NAFLD pathogenesis. Lingonberry (Vaccinium vitis-idaea L.) is rich in anthocyanins that have antioxidant and anti-inflammatory properties. The present study investigated the effect of lingonberry supplementation on liver injury in C57BL/6J male mice fed a high-fat diet (HFD) for 12 weeks. Mice fed HFD displayed liver injury with steatosis, increased lipid peroxidation and inflammatory cytokine expression in the liver as compared to mice fed a control diet. Lingonberry supplementation for 12 weeks alleviated HFD-induced liver injury, attenuated hepatic lipid accumulation, and inflammatory cytokine expression. Lingonberry supplementation inhibited the expression of sterol regulatory element-binding protein-1c (SREBP-1c) and acetyl-CoA carboxylase-1 (AAC-1) as well as activated AMP-activated protein kinase (AMPK) in the liver. It also decreased HFD-induced hepatic oxidative stress and aggregation of inflammatory foci. This was associated with a restoration of nuclear factor erythroid 2–related factor 2 (Nrf2) and glutathione level in the liver. These results suggest that lingonberry supplementation can protect against HFD-induced liver injury partly through attenuation of hepatic lipid accumulation, oxidative stress, and inflammatory response.

Fluoxetine-induced Hepatic Lipid Accumulation is Linked to Elevated Serotonin Production

2021 ◽  
Author(s):  
Ahmed Ayyash ◽  
Alison C Holloway
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Lipid Accumulation ◽  
Fatty Liver Disease ◽  
Metabolic Effects ◽  
Serotonin Synthesis ◽  
Alcoholic Fatty Liver ◽  
Hepatic Lipid ◽  
Hepatic Lipid Accumulation ◽  
Alcoholic Fatty Liver Disease

Fluoxetine, a commonly prescribed selective serotonin reuptake inhibitor antidepressant, has been shown to increase hepatic lipid accumulation, a key factor in the development of non-alcoholic fatty liver disease. Interestingly, fluoxetine has also been reported to increase peripheral serotonin synthesis. As emerging evidence suggests that serotonin may be involved in the development of non-alcoholic fatty liver disease we sought to determine if fluoxetine-induced hepatic lipid accumulation is mediated via altered serotonin production. Fluoxetine treatment increased lipid accumulation in association with increased mRNA expression of tryptophan hydroxylase 1 (<i>Tph1, serotonin biosynthetic enzyme) and intracellular serotonin content. Serotonin alone had a similar effect to increase lipid accumulation. Moreover, blocking serotonin synthesis reversed the fluoxetine-induced increases in lipid accumulation. Collectively, these data suggest that fluoxetine induced lipid accumulation can be mediated, in part, by elevated serotonin production. These results suggest a potential therapeutic target to ameliorate the adverse metabolic effects of fluoxetine exposure.

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