scholarly journals The Combination of Berberine, Tocotrienols and Coffee Extracts Improves Metabolic Profile and Liver Steatosis by the Modulation of Gut Microbiota and Hepatic miR-122 and miR-34a Expression in Mice

Nutrients ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 1281
Author(s):  
Valentina Cossiga ◽  
Vincenzo Lembo ◽  
Cecilia Nigro ◽  
Paola Mirra ◽  
Claudia Miele ◽  
...  
Keyword(s):  
Hepatic Steatosis ◽  
Plant Extracts ◽  
Elaeis Guineensis ◽  
Low Density Lipoprotein ◽  
Liver Steatosis ◽  
Density Lipoprotein ◽  
Coffea Canephora ◽  
Standard Diet ◽  
Microbial Composition ◽  
Alcoholic Fatty Liver

Non-alcoholic-fatty liver disease (NAFLD) is spreading worldwide. Specific drugs for NAFLD are not yet available, even if some plant extracts show beneficial properties. We evaluated the effects of a combination, composed by Berberis Aristata, Elaeis Guineensis and Coffea Canephora, on the development of obesity, hepatic steatosis, insulin-resistance and on the modulation of hepatic microRNAs (miRNA) levels and microbiota composition in a mouse model of liver damage. C57BL/6 mice were fed with standard diet (SD, n = 8), high fat diet (HFD, n = 8) or HFD plus plant extracts (HFD+E, n = 8) for 24 weeks. Liver expression of miR-122 and miR-34a was evaluated by quantitativePCR. Microbiome analysis was performed on cecal content by 16S rRNA sequencing. HFD+E-mice showed lower body weight (p < 0.01), amelioration of insulin-sensitivity (p = 0.021), total cholesterol (p = 0.014), low-density-lipoprotein-cholesterol (p < 0.001), alanine-aminotransferase (p = 0.038) and hepatic steatosis compared to HFD-mice. While a decrease of hepatic miR-122 and increase of miR-34a were observed in HFD-mice compared to SD-mice, both these miRNAs had similar levels to SD-mice in HFD+E-mice. Moreover, a different microbial composition was found between SD- and HFD-mice, with a partial rescue of dysbiosis in HFD+E-mice. This combination of plant extracts had a beneficial effect on HFD-induced NAFLD by the modulation of miR-122, miR-34a and gut microbiome.

scholarly journals Berberis aristata, Elaeis guineensis and Coffea canephora Extracts Modulate the Insulin Receptor Expression and Improve Hepatic Steatosis in NAFLD Patients: A Pilot Clinical Trial

Nutrients ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 3070
Author(s):  
Valentina Cossiga ◽  
Vincenzo Lembo ◽  
Maria Guarino ◽  
Concetta Tuccillo ◽  
Federica Morando ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Receptor ◽  
Hepatic Steatosis ◽  
Plant Extracts ◽  
Elaeis Guineensis ◽  
Transient Elastography ◽  
Coffea Canephora ◽  
Receptor Expression ◽  
Model Assessment ◽  
Alcoholic Fatty Liver

Non-alcoholic fatty liver disease (NAFLD) is associated with insulin resistance and diabetes. A reduction in insulin receptor (IR) expression has been reported in these patients. The aims of this study were to evaluate the effects of a mixture of plant extracts consisting of Berberis aristata, Elaeis guineensis and decaffeinated green coffee by Coffea canephora on the improvement of glycaemic profile, through the modulation of IR levels, and of hepatic steatosis in NAFLD patients. Forty-nine patients with a grade of steatosis S1-S2 were randomly allocated to the treatment with plant extracts or placebo for six months. Hepatic steatosis was evaluated using transient elastography with CAP (controlled attenuation parameter). Glucose, insulin, and IR levels were measured in serum samples. At the end of the study, patients treated with plant extracts displayed a significant reduction of serum glucose (p < 0.001), insulin levels (p < 0.01), homeostatic model assessment for insulin resistance (HOMA-IR) index (p < 0.001), and CAP value (p < 0.01) compared to placebo. Moreover, the IR expression was increased significantly in the plant extracts group compared to the placebo group (p < 0.05). The combination of plant extracts increases serum IR levels, determining amelioration of glycemic profile and improvement of hepatic steatosis in NAFLD patients.

scholarly journals miRNA-132 induces hepatic steatosis and hyperlipidaemia by synergistic multitarget suppression

Gut ◽  
2017 ◽  
Vol 67 (6) ◽  
pp. 1124-1134 ◽  
Author(s):  
Geula Hanin ◽  
Nadav Yayon ◽  
Yonat Tzur ◽  
Rotem Haviv ◽  
Estelle R Bennett ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Fatty Liver ◽  
Hepatic Steatosis ◽  
Mouse Models ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Obese Mice ◽  
Alcoholic Fatty Liver

ObjectiveBoth non-alcoholic fatty liver disease (NAFLD) and the multitarget complexity of microRNA (miR) suppression have recently raised much interest, but the in vivo impact and context-dependence of hepatic miR-target interactions are incompletely understood. Assessing the relative in vivo contributions of specific targets to miR-mediated phenotypes is pivotal for investigating metabolic processes.DesignWe quantified fatty liver parameters and the levels of miR-132 and its targets in novel transgenic mice overexpressing miR-132, in liver tissues from patients with NAFLD, and in diverse mouse models of hepatic steatosis. We tested the causal nature of miR-132 excess in these phenotypes by injecting diet-induced obese mice with antisense oligonucleotide suppressors of miR-132 or its target genes, and measured changes in metabolic parameters and transcripts.ResultsTransgenic mice overexpressing miR-132 showed a severe fatty liver phenotype and increased body weight, serum low-density lipoprotein/very low-density lipoprotein (LDL/VLDL) and liver triglycerides, accompanied by decreases in validated miR-132 targets and increases in lipogenesis and lipid accumulation-related transcripts. Likewise, liver samples from both patients with NAFLD and mouse models of hepatic steatosis or non-alcoholic steatohepatitis (NASH) displayed dramatic increases in miR-132 and varying decreases in miR-132 targets compared with controls. Furthermore, injecting diet-induced obese mice with anti-miR-132 oligonucleotides, but not suppressing its individual targets, reversed the hepatic miR-132 excess and hyperlipidemic phenotype.ConclusionsOur findings identify miR-132 as a key regulator of hepatic lipid homeostasis, functioning in a context-dependent fashion via suppression of multiple targets and with cumulative synergistic effects. This indicates reduction of miR-132 levels as a possible treatment of hepatic steatosis.

Resveratrol Ameliorates Alcoholic Fatty Liver by Inducing Autophagy

2016 ◽  
Vol 44 (06) ◽  
pp. 1207-1220 ◽  
Author(s):  
Liying Tang ◽  
Fengli Yang ◽  
Zhirui Fang ◽  
Chengmu Hu
Keyword(s):  
Fatty Liver ◽  
Hepatic Steatosis ◽  
Lipid Accumulation ◽  
Early Stage ◽  
Low Density Lipoprotein ◽  
Specific Inhibitor ◽  
Density Lipoprotein ◽  
Protective Effects ◽  
Alcoholic Fatty Liver

Alcoholic fatty liver (AFL) is early stage of alcoholic liver disease, which can progress to steatohepatitis, fibrosis, and cirrhosis if alcohol consumption is continued. The pathogenesis of AFL is associated with excessive lipid accumulation in hepatocytes. Resveratrol (RES), a dietary polyphenol found in red wines and grapes, has been shown to have a hepatoprotective effect. Autophagy is a crucial physiological process in cellular catabolism that involves the regulation of lipid droplets. Autophagy maintains a balance between protein synthesis, degradation and self-recycling. In the present study, we evaluated the protective effects of RES (10[Formula: see text]mg/kg, 30[Formula: see text]mg/kg, 100[Formula: see text]mg/kg) on AFL mice fed with an ethanol Lieber-DeCarli liquid diet, and HepG2 cells in the presence of oleic acid and alcohol to investigate whether resveratrol could induce autophagy to attenuate lipid accumulation. The results showed that RES (30[Formula: see text]mg/kg and 100[Formula: see text]mg/kg) treatment significantly attenuated hepatic steatosis and lowered the activities of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), low density lipoprotein cholesterol (LDL-C). H&E staining showed that RES reduced hepatic lipid accumulation. Transmission electron microscopy (TEM) images showed that RES treatment increased the number of autophagosomes and promoted the formation of autophagy. Western blot analysis showed that RES treatment increased the levels of microtubule-associated protein light chain3- II (LC3-II) and Beclin1, decreased expression of p62 protein. In addition, in vitro studies also demonstrated that RES led to the formation of acidic vesicular organelles (AVOs), however, 3-Methyladenine (3-MA), a specific inhibitor of autophagy, obviously inhibited the above effects of RES. In conclusion, RES has protective effects on alcoholic hepatic steatosis, and the potential mechanism might be involved in inducing autophagy.

scholarly journals The liver steatosis severity and lipid characteristics in primary biliary cholangitis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yuan Zhang ◽  
Xing Hu ◽  
Jing Chang ◽  
Jie Chen ◽  
Xue Han ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatic Steatosis ◽  
Healthy Subjects ◽  
Cardiovascular Events ◽  
Liver Steatosis ◽  
Density Lipoprotein ◽  
Primary Biliary Cholangitis ◽  
Lipid Levels ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

Abstract Background Patients with primary biliary cholangitis (PBC) often have comorbid dyslipidemia, and determining the degree of hepatic steatosis can help predict the risk of cardiovascular events in PBC patients. The aim of our study was to analyze the characteristics of lipid distribution and the degree of hepatic steatosis in PBC. Methods We retrospectively analyzed 479 cases of PBC, chronic hepatitis B (CHB), chronic hepatitis C (CHC), non-alcoholic fatty liver disease (NAFLD), and healthy subjects (Normal) diagnosed by liver biopsy or definitive clinical diagnosis. Controlled attenuation parameter (CAP) values were applied to assess the degree of steatosis of the liver, and lipid levels were also compared in the five cohorts. Results We found that among the five groups of subjects, the PBC group had the lowest CAP values (P < 0.001), and the high-density lipoprotein cholesterol (HDL-C) level in the PBC group was higher than normal, CHC and CHB group (P = 0.004, P = 0.033, P < 0.001, respectively).In the multivariate linear analysis, only BMI (β = 1.280, P = 0.028), ALP (β = − 0.064, P = 0.012), TBA (β = − 0.126, P = 0.020), TG (β = 12.520, P = 0.000), HDL-C (β = − 11.338, P = 0.001) and LDL-C (β = 7.012, P = 0.002) were independent predictors of CAP. Conclusions Among PBC, CHB, CHC, NAFLD and healthy subjects, PBC had the lowest degree of hepatic steatosis and higher HDL-C levels, all of which were found to be protective factors against atherosclerosis and cardiovascular risk and would provide a valuable reference for the risk of developing cardiovascular events in PBC patients.

scholarly journals Sulforaphane ameliorates lipid profile in rodents: an updated systematic review and meta-analysis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kaili Du ◽  
Yuxin Fan ◽  
Dan Li
Keyword(s):  
Systematic Review ◽  
Weight Control ◽  
Weighted Mean Difference ◽  
Meta Analysis ◽  
Low Density Lipoprotein ◽  
Disease Model ◽  
Density Lipoprotein ◽  
Liver Weight ◽  
Lipoprotein Cholesterol ◽  
Alcoholic Fatty Liver

AbstractSulforaphane (SFN), a naturally-occurring isothiocyanate enriched in cabbage and broccoli, has been provided as food supplements to improve weight management and reduce lipid levels. However, its effects on serum lipid profiles are contradictory. In this review, a meta-analysis and systematic review of SFN on lipid reduction and weight control is assessed with mice and rats fed on high-fat diet. The effects of SFN supplementation were evaluated by weighted mean difference (WMD) in body weight (BW), liver weight (LW) and also by its effect on serum lipids. A random-effects model was applied to estimate the overall summary effect. SFN reduced BW (WMD: − 2.76 g, 95% CI: − 4.19, − 1.34) and LW (WMD: − 0.93 g, 95% CI: − 1.63, − 0.23) significantly in our ten trials. Its effects on serum total cholesterol (TC) (WMD: − 15.62 mg/dL, 95% CI: − 24.07, − 7.18), low-density lipoprotein cholesterol (LDL-C) (WMD: − 8.35 mg/dL, 95% CI: − 15.47, − 1.24) and triglyceride (TG) (WMD: − 40.85 mg/dL, 95% CI: − 67.46, − 14.24) were significant except for high-density lipoprotein cholesterol (HDL-C) component (WMD: 1.05 mg/dL, 95% CI: − 3.44, 5.54). However, species, disease model, duration, SFN dosage as well as route of administration did not explain the heterogeneity among studies. In summary, these findings provide new insights concerning preclinical strategies for treating diseases including obesity, diabetes, hypertension, non-alcoholic fatty liver disease as well as cardiovascular disease with SFN supplements.

scholarly journals Mitochondrial Lipid Homeostasis at the Crossroads of Liver and Heart Diseases

2021 ◽  
Vol 22 (13) ◽  
pp. 6949
Author(s):  
Siarhei A. Dabravolski ◽  
Evgeny E. Bezsonov ◽  
Mirza S. Baig ◽  
Tatyana V. Popkova ◽  
Alexander N. Orekhov
Keyword(s):  
Heart Diseases ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Liver Mitochondria ◽  
Atherogenic Dyslipidemia ◽  
Cvd Risk ◽  
Alcoholic Fatty Liver ◽  
Cholesterol Levels ◽  
Mitochondrial Lipid ◽  
Cardioprotective Effects

The prevalence of NAFLD (non-alcoholic fatty liver disease) is a rapidly increasing problem, affecting a huge population around the globe. However, CVDs (cardiovascular diseases) are the most common cause of mortality in NAFLD patients. Atherogenic dyslipidemia, characterized by plasma hypertriglyceridemia, increased small dense LDL (low-density lipoprotein) particles, and decreased HDL-C (high-density lipoprotein cholesterol) levels, is often observed in NAFLD patients. In this review, we summarize recent genetic evidence, proving the diverse nature of metabolic pathways involved in NAFLD pathogenesis. Analysis of available genetic data suggests that the altered operation of fatty-acid β-oxidation in liver mitochondria is the key process, connecting NAFLD-mediated dyslipidemia and elevated CVD risk. In addition, we discuss several NAFLD-associated genes with documented anti-atherosclerotic or cardioprotective effects, and current pharmaceutical strategies focused on both NAFLD treatment and reduction of CVD risk.

scholarly journals Hepatic Steatosis Is Associated with Elevated Serum Iron in Patients with Obesity and Improves after Laparoscopic Sleeve Gastrectomy

Obesity Facts ◽  
2020 ◽  
pp. 1-8
Author(s):  
Bingwei Ma ◽  
Hang Sun ◽  
Bing Zhu ◽  
Shilin Wang ◽  
Lei Du ◽  
...  
Keyword(s):  
Sleeve Gastrectomy ◽  
Laparoscopic Sleeve Gastrectomy ◽  
Hepatic Steatosis ◽  
Elevated Serum ◽  
Density Lipoprotein ◽  
Postprandial Blood Glucose ◽  
Iron Level ◽  
Metabolic Markers ◽  
Alcoholic Fatty Liver ◽  
Negatively Associated

<b><i>Background:</i></b> Iron is closely related to metabolism. However, the relationship between iron and hepatic steatosis has not been fully elucidated. <b><i>Objective:</i></b> We aimed to investigate the triangular relationship between iron and hepatic steatosis and laparoscopic sleeve gastrectomy (LSG) in patients with obesity. <b><i>Methods:</i></b> A total of 297 patients with obesity and 43 healthy individuals with a normal BMI were enrolled. Eighty-two patients underwent LSG. Anthropometrics, glucose-lipid metabolic markers, and hepatic steatosis assessed by FibroScan (CAP value and E value) were measured at baseline, and again at follow-up time intervals of 6 months and 1 year after surgery. <b><i>Results:</i></b> (1) Iron was significantly higher in patients with obesity or overweight than in the individuals with normal BMI (8.18 ± 1.47 vs. 7.46 ± 0.99 mmol/L, <i>p</i> = 0.002). Iron was also higher in subjects with high blood pressure, dyslipidemia, and hyperuricemia than non-corresponding disorders (all <i>p</i> &#x3c; 0.05). Moreover, iron was significantly higher in the severe than mild or moderate non-alcoholic fatty liver disease (NAFLD) group (<i>p</i> = 0.046 and 0.018). (2) Iron was positively associated with body weight, BMI, waist-to-hip ratio, uric acid, liver enzymes, postprandial blood glucose, fasting insulin, HOMA-IR, triglycerides, free fatty acid, and hepatic steatosis (CAP value), and negatively associated with high-density lipoprotein cholesterol (all <i>p</i> &#x3c; 0.05). Iron was also positively associated with the visceral adipose area in patients with obesity and negatively associated with the subcutaneous adipose area in patients with overweight (all <i>p</i> &#x3c; 0.05). (3) Iron levels and CAP values were decreased gradually 6 months and 1 year after surgery (all <i>p</i> &#x3c; 0.05). <b><i>Conclusions:</i></b> Overall, our results indicated that iron is associated with hepatic steatosis in obesity. The iron level was significantly higher in patients with severe NAFLD than with mild or moderate NAFLD. LSG may reduce iron levels while improving fat deposition in the liver.

scholarly journals Deficiency of ASGR1 in pigs recapitulates reduced risk factor for cardiovascular disease in humans

PLoS Genetics ◽  
2021 ◽  
Vol 17 (11) ◽  
pp. e1009891
Author(s):  
Baocai Xie ◽  
Xiaochen Shi ◽  
Yan Li ◽  
Bo Xia ◽  
Jia Zhou ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
De Novo ◽  
Cholesterol Metabolism ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Atherogenic Diet ◽  
Standard Diet ◽  
Low Levels ◽  
Reduced Risk

Genetic variants in the asialoglycoprotein receptor 1 (ASGR1) are associated with a reduced risk of cardiovascular disease (CVD) in humans. However, the underlying molecular mechanism remains elusive. Given the cardiovascular similarities between pigs and humans, we generated ASGR1-deficient pigs using the CRISPR/Cas9 system. These pigs show age-dependent low levels of non-HDL-C under standard diet. When received an atherogenic diet for 6 months, ASGR1-deficient pigs show lower levels of non-HDL-C and less atherosclerotic lesions than that of controls. Furthermore, by analysis of hepatic transcriptome and in vivo cholesterol metabolism, we show that ASGR1 deficiency reduces hepatic de novo cholesterol synthesis by downregulating 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), and increases cholesterol clearance by upregulating the hepatic low-density lipoprotein receptor (LDLR), which together contribute to the low levels of non-HDL-C. Despite the cardioprotective effect, we unexpectedly observed mild to moderate hepatic injury in ASGR1-deficient pigs, which has not been documented in humans with ASGR1 variants. Thus, targeting ASGR1 might be an effective strategy to reduce hypercholesterolemia and atherosclerosis, whereas further clinical evidence is required to assess its hepatic impact.

Abstract P080: Fructose Acutely Increases Size of Very Low Density Lipoprotein In Adolescents With Hepatic Steatosis

Circulation ◽  
2014 ◽  
Vol 129 (suppl_1) ◽  
Author(s):  
Mirian Vos ◽  
Ran Jin ◽  
Jean Welsh ◽  
Ngoc-Anh Le
Keyword(s):  
Hepatic Steatosis ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Cardiovascular Complications ◽  
Plasma Lipoproteins ◽  
Healthy Children ◽  
Mri Imaging ◽  
Nonalcoholic Fatty Liver ◽  
Obese Adolescents ◽  
Acute Response

Introduction: Cardiovascular complications are a leading cause of mortality in nonalcoholic fatty liver disease (NAFLD). Fructose has been reported to be associated with dyslipidemia and increased cardiovascular risk in adults but its impact on adolescents with NAFLD is not well understood. We previously demonstrated that fructose disproportionately increased postprandial hypertriglyceridemia in pediatric NAFLD as compared to healthy children. However, the mechanism remains unclear. Hypothesis: We hypothesized that fructose would contribute to hypertriglyceridemia in pediatric NAFLD by increasing the size of VLDL particles. Methods: We examined the acute response to a single dose of fructose beverage in 50 Hispanic-American obese adolescents with varying degrees of hepatic steatosis. Those with hepatic fat >5% on MRI imaging were designated as presumed NAFLD. Subjects consumed a 12oz drink containing 33g of fructose and plasma samples were collected at baseline and 30, 60, and 90 minutes afterwards. Plasma lipoproteins were measured using NMR (Liposcience, Raleigh, NC). Results: In response to acute fructose load, subjects without NAFLD increased the total number of TG rich lipoprotein particles (p = 0.047). However, this increase was not observed in subjects with NAFLD; instead, they increased the subpopulation of large VLDL particles (p = 0.008) and the mean size of VLDL particles (p = 0.004) (Figure 1). In line with this finding, TG-to-apoB ratio significantly increased in subjects with NAFLD (2.25 ± 0.26 to 2.37 ± 0.25, p = 0.031) but not in non-NAFLD. Conclusions: These findings demonstrate that adolescents with NAFLD have more atherogenic, large VLDL in response to fructose compared to obese adolescents without NAFLD. Dietary fructose restriction may be a critical component in the treatment of NAFLD associated cardiovascular disease and should be tested further.

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