scholarly journals Effect of genetic and environmental influences on hepatic steatosis: A classical twin study based on computed tomography

Imaging ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 15-20
Author(s):  
György Jermendy ◽  
Márton Kolossváry ◽  
Ibolya Dudás ◽  
Ádám L. Jermendy ◽  
Alexisz Panajotu ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Environmental Factors ◽  
Hepatic Steatosis ◽  
Lipid Accumulation ◽  
Twin Study ◽  
Structural Equation ◽  
Environmental Influence ◽  
Environmental Influences ◽  
Hepatic Lipid ◽  
Hepatic Lipid Accumulation

AbstractBackground and aimsNon-alcoholic fatty liver disease (NAFLD) increases cardiovascular morbidity and mortality, and carries poor long-term hepatic prognosis. Data about the role of genetic and environmental factors in the hepatic lipid accumulation are limited. The aim of the study was to evaluate the genetic and environmental impact on the hepatic lipid accumulation within a cohort of adult twin pairs.Patients and methodsWe investigated 182 twin subjects [monozygotic (MZ, n = 114) and dizygotic (DZ, n = 68) same-gender twins (age 56.0 ± 9.6 years; BMI 27.5 ± 5.0 kg/m2; females 65.9%)] who underwent computed tomography (CT) with a 256-slice scanner. Using non-enhanced CT-images, we calculated the average value of hepatic attenuation [expressed in Hounsfield unit (HU)] suggesting hepatic lipid content. Crude data were adjusted to age, sex, BMI and HbA1c values. Intra-pair correlations were established, and structural equation models were used for quantifying the contribution of additive genetic (A), common environmental (C) and unique environmental (E) components to the investigated phenotype.ResultsThe study cohort represented a moderately overweight, middle-aged Caucasian population. There was no significant difference between MZ and DZ twin subjects regarding hepatic CT-attenuation (57.9 ± 12.6 HU and 59.3 ± 11.7 HU, respectively; p = 0.747). Age, sex, BMI and HbA1c adjusted co-twin correlations between the siblings showed that MZ twins have stronger correlations of HU values than DZ twins (rMZ = 0.592, p < 0.001; rDZ = 0.047, p = 0.690, respectively). Using the structural equation model, a moderate additive genetic dependence (A: 38%, 95% CI 15–58%) and a greater unique environmental influence (E: 62%, 95% CI 42–85%) was found. Common environmental influence was not identified (C: 0%).ConclusionThe results of our classical CT-based twin study revealed moderate genetic and greater environmental influences on the phenotypic appearance of hepatic steatosis, commonly referred to as NAFLD. Favorable changes of modifiable environmental factors are of great importance in preventing or treating NAFLD.

Ellagic acid ameliorates AKT-driven hepatic steatosis in mice by suppressing de novo lipogenesis via the AKT/SREBP-1/FASN pathway

2019 ◽  
Vol 10 (6) ◽  
pp. 3410-3420 ◽  
Author(s):  
Cong Zhang ◽  
Junjie Hu ◽  
Lei Sheng ◽  
Ming Yuan ◽  
Yong Wu ◽  
...  
Keyword(s):  
Hepatic Steatosis ◽  
Ellagic Acid ◽  
Lipid Accumulation ◽  
De Novo ◽  
De Novo Lipogenesis ◽  
Hepatic Lipid ◽  
Hepatic Lipid Accumulation

Ellagic acid alleviates hepatic lipid accumulation in mice by suppressing AKT-driven de novo lipogenesis.

scholarly journals Hepatitis B Virus X Protein Induces Hepatic Steatosis by Enhancing the Expression of Liver Fatty Acid Binding Protein

2015 ◽  
Vol 90 (4) ◽  
pp. 1729-1740 ◽  
Author(s):  
Yun-li Wu ◽  
Xian-e Peng ◽  
Yi-bing Zhu ◽  
Xiao-li Yan ◽  
Wan-nan Chen ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Transgenic Mice ◽  
Hepatic Steatosis ◽  
Lipid Accumulation ◽  
Fatty Acid Binding Protein ◽  
Liver Fatty Acid ◽  
Fatty Acid Binding ◽  
Hepatic Lipid ◽  
Hepatic Lipid Accumulation ◽  
Acid Binding Protein

ABSTRACTHepatitis B virus (HBV) has been implicated as a potential trigger of hepatic steatosis although molecular mechanisms involved in the pathogenesis of HBV-associated hepatic steatosis still remain elusive. Our prior work has revealed that the expression level of liver fatty acid binding protein 1 (FABP1), a key regulator of hepatic lipid metabolism, was elevated in HBV-producing hepatoma cells. In this study, the effects of HBV X protein (HBx) mediated FABP1 regulation on hepatic steatosis and the underlying mechanism were determined. mRNA and protein levels of FABP1 were measured by quantitative RT-PCR (qPCR) and Western blotting. HBx-mediated FABP1 regulation was evaluated by luciferase assay, coimmunoprecipitation, and chromatin immunoprecipitation. Hepatic lipid accumulation was measured by using Oil-Red-O staining and the triglyceride level. It was found that expression of FABP1 was increased in HBV-producing hepatoma cells, the sera of HBV-infected patients, and the sera and liver tissues of HBV-transgenic mice. Ectopic overexpression of HBx resulted in upregulation of FABP1 in HBx-expressing hepatoma cells, whereas HBx abolishment reduced FABP1 expression. Mechanistically, HBx activated the FABP1 promoter in an HNF3β-, C/EBPα-, and PPARα-dependent manner, in which HBx increased the gene expression of HNF3β and physically interacted with C/EBPα and PPARα. On the other hand, knockdown of FABP1 remarkably blocked lipid accumulation both in long-chain free fatty acids treated HBx-expressing HepG2 cells and in a high-fat diet-fed HBx-transgenic mice. Therefore, FABP1 is a key driver gene in HBx-induced hepatic lipid accumulation via regulation of HNF3β, C/EBPα, and PPARα. FABP1 may represent a novel target for treatment of HBV-associated hepatic steatosis.IMPORTANCEAccumulating evidence from epidemiological and experimental studies has indicated that chronic HBV infection is associated with hepatic steatosis. However, the molecular mechanism underlying HBV-induced pathogenesis of hepatic steatosis still remains to be elucidated. In this study, we found that expression of liver fatty acid binding protein (FABP1) was dramatically increased in the sera of HBV-infected patients and in both sera and liver tissues of HBV-transgenic mice. Forced expression of HBx led to FABP1 upregulation, whereas knockdown of FABP1 remarkably diminished lipid accumulation in bothin vitroandin vivomodels. It is possible that HBx promotes hepatic lipid accumulation through upregulating FABP1 in the development of HBV-induced nonalcoholic fatty liver disease. Therefore, inhibition of FABP1 might have therapeutic value in steatosis-associated chronic HBV infection.

scholarly journals Role of β-adrenergic receptors in regulation of hepatic fat accumulation during aging

2012 ◽  
Vol 213 (3) ◽  
pp. 251-261 ◽  
Author(s):  
Paramita M Ghosh ◽  
Zhen-Ju Shu ◽  
Bing Zhu ◽  
Zhongding Lu ◽  
Yuji Ikeno ◽  
...  
Keyword(s):  
Adenylyl Cyclase ◽  
Hepatic Steatosis ◽  
Lipid Content ◽  
Lipid Accumulation ◽  
Adenylyl Cyclase Activity ◽  
Fat Accumulation ◽  
Hepatic Lipid ◽  
Hepatic Lipid Accumulation ◽  
Hepatic Fat

Excessive fat accumulation in liver (hepatic steatosis) predisposes to hepatic functional and structural impairment and overall metabolic risk. Previous studies noted an association between hepatic steatosis and age in humans and rodents. However, the mechanisms leading to age-associated hepatic fat accumulation remain unknown. Earlier work from our group showed that β-adrenergic receptor (β-AR) levels and β-AR-stimulated adenylyl cyclase activity increase in rat liver during aging. Here we investigated whether age-associated increases in β-AR signaling play a role in augmenting hepatic lipid accumulation. We demonstrate an increase in hepatic lipid content during senescence and a significant correlation between hepatic fat content and stimulation of adenylyl cyclase activity by the β-AR agonist isoproterenol in rat liver. Isoproterenol administration to young and old rodents in vivo increased hepatic lipid accumulation. Furthermore, in vitro overexpression of β1- and β2-AR subtypes in hepatocytes from young rodents increased cellular lipid content, whereas inhibition of β-ARs by receptor subtype-specific inhibitors reduced lipid levels in hepatocytes from senescent animals. Isoproterenol-induced hepatic lipid accumulation in vivo was prevented by the β-AR nonselective blocker propranolol, suggesting a novel therapeutic effect of this class of drugs in hepatic steatosis. Acipimox, which inhibits adipose tissue lipolysis, did not alter isoproterenol-mediated hepatic fat accumulation; thus β-AR responsive hepatic lipid accumulation does not appear to be related primarily to altered lipolysis. These findings suggest that augmented hepatic β-AR signaling during aging may increase lipid accumulation in liver and advocate a possible role for β-adrenergic blockers in preventing or retarding the development of hepatic steatosis.

scholarly journals Neuronal modulation of hepatic lipid accumulation induced by bingelike drinking

2020 ◽  
Vol 318 (5) ◽  
pp. E655-E666
Author(s):  
Maria Ibars ◽  
Matthew T. Maier ◽  
Ernie Yulyaningsih ◽  
Luz Perez ◽  
Rachel Cheang ◽  
...  
Keyword(s):  
Alcohol Consumption ◽  
Fatty Liver ◽  
Hepatic Steatosis ◽  
Lipid Accumulation ◽  
Excessive Alcohol Consumption ◽  
Hepatic Lipid ◽  
Hepatic Lipid Accumulation ◽  
Excessive Alcohol ◽  
Sympathetic Nervous ◽  
The Brain

Excessive alcohol consumption, including binge drinking, is a common cause of fatty liver disease. Binge drinking rapidly induces hepatic steatosis, an early step in the pathogenesis of chronic liver injury. Despite its prevalence, the process by which excessive alcohol consumption promotes hepatic lipid accumulation remains unclear. Alcohol exerts potent effects on the brain, including hypothalamic neurons crucial for metabolic regulation. However, whether or not the brain plays a role in alcohol-induced hepatic steatosis is unknown. In the brain, alcohol increases extracellular levels of adenosine, a potent neuromodulator, and previous work implicates adenosine signaling as being important for the development of alcoholic fatty liver disease. Acute alcohol exposure also increases both the activity of agouti-related protein (AgRP)-expressing neurons and AgRP immunoreactivity. Here, we show that adenosine receptor A2B signaling in the brain modulates the extent of alcohol-induced fatty liver in mice and that both the AgRP neuropeptide and the sympathetic nervous system are indispensable for hepatic steatosis induced by bingelike alcohol consumption. Together, these results indicate that the brain plays an integral role in alcohol-induced hepatic lipid accumulation and that central adenosine signaling, hypothalamic AgRP, and the sympathetic nervous system are crucial mediators of this process.

scholarly journals Dapagliflozin Alleviates Hepatic Steatosis by Restoring Autophagy via the AMPK-mTOR Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Liuran Li ◽  
Qinghua Li ◽  
Wenbin Huang ◽  
Yibing Han ◽  
Huiting Tan ◽  
...  
Keyword(s):  
Hepatic Steatosis ◽  
Lipid Accumulation ◽  
Hepg2 Cells ◽  
Mtor Pathway ◽  
Hepatic Lipid ◽  
Hepatic Lipid Accumulation ◽  
Zdf Rats ◽  
Oxidation Enzyme

As a newly approved oral hypoglycaemic agent, the sodium-glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin, which is derived from the natural product phlorizin can effectively reduce blood glucose. Recent clinical studies have found that dapagliflozin alleviates non-alcoholic fatty liver disease (NAFLD), but the specific mechanism remains to be explored. This study aimed to investigate the underlying mechanism of dapagliflozin in alleviating hepatocyte steatosis in vitro and in vivo. We fed the spontaneous type 2 diabetes mellitus rats with high-fat diets and cultured human normal liver LO2 cells and human hepatocellular carcinoma HepG2 cells with palmitic acid (PA) to induce hepatocellular steatosis. Dapagliflozin attenuated hepatic lipid accumulation both in vitro and in vivo. In Zucker diabetic fatty (ZDF) rats, dapagliflozin reduced hepatic lipid accumulation via promoting phosphorylation of acetyl-CoA carboxylase 1 (ACC1), and upregulating lipid β-oxidation enzyme acyl-CoA oxidase 1 (ACOX1). Furthermore, dapagliflozin increased the expression of the autophagy-related markers LC3B and Beclin1, in parallel with a drop in p62 level. Similar effects were observed in PA-stimulated LO2 cells and HepG2 cells. Dapagliflozin treatment could also significantly activated AMPK and reduced the phosphorylation of mTOR in ZDF rats and PA-stimulated LO2 cells and HepG2 cells. We demonstrated that dapagliflozin ameliorates hepatic steatosis by decreasing lipogenic enzyme, while inducing fatty acid oxidation enzyme and autophagy, which could be associated with AMPK activation. Moreover, our results indicate that dapagliflozin induces autophagy via the AMPK-mTOR pathway. These findings reveal a novel clinical application and functional mechanism of dapagliflozin in the treatment of NAFLD.

scholarly journals Gallic Acid Inhibits Lipid Accumulation via AMPK Pathway and Suppresses Apoptosis and Macrophage-Mediated Inflammation in Hepatocytes

Nutrients ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1479
Author(s):  
Miori Tanaka ◽  
Akari Sato ◽  
Yoshimi Kishimoto ◽  
Hideaki Mabashi-Asazuma ◽  
Kazuo Kondo ◽  
...  
Keyword(s):  
Liver Disease ◽  
Gallic Acid ◽  
Hepatic Steatosis ◽  
Lipid Accumulation ◽  
Molecular Mechanisms ◽  
Nonalcoholic Fatty Liver ◽  
Hepatic Lipid ◽  
Hepatic Lipid Accumulation ◽  
Apoptosis And Inflammation ◽  
Amp Activated Protein Kinase

Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease, sometimes ranges from simple steatosis to nonalcoholic steatohepatitis (NASH). Various hits including excessive hepatic steatosis, oxidative stress, apoptosis, and inflammation, contribute to NASH development. Gallic acid (GA), a natural polyphenol, was reported to exert a protective effect on hepatic steatosis in animal models, but the precise molecular mechanisms remain unclear. Here, we examined the effect of GA on hepatic lipid accumulation, apoptosis, and inflammatory response caused by hepatocyte–macrophage crosstalk. We demonstrated that GA attenuated palmitic acid (PA)-induced fat accumulation via the activation of AMP-activated protein kinase (AMPK) in HepG2 cells. GA also ameliorated cell viability and suppressed apoptosis-related gene expression and caspase 3/7 activity induced by PA and H2O2. In a co-culture of lipid-laden Hepa 1-6 hepatocytes and RAW 264 macrophages, GA reduced inflammatory mediator expression and induced antioxidant enzyme expression. These results indicate that GA suppresses hepatic lipid accumulation, apoptosis, and inflammation caused by the interaction between hepatocytes and macrophages. The potential effects of GA observed in our study could be effective in preventing NASH and its complications.

scholarly journals ERK-dependent mTOR pathway is involved in berberine-induced autophagy in hepatic steatosis

2016 ◽  
Vol 57 (4) ◽  
pp. 251-260 ◽  
Author(s):  
Qin He ◽  
Dan Mei ◽  
Sha Sha ◽  
Shanshan Fan ◽  
Lin Wang ◽  
...  
Keyword(s):  
Hepatic Steatosis ◽  
Lipid Accumulation ◽  
Mtor Pathway ◽  
Mice Model ◽  
Alcoholic Fatty Liver ◽  
Hepatic Lipid ◽  
Hepatic Lipid Accumulation ◽  
Positive Effects

Non-alcoholic fatty liver disease (NAFLD) is a burgeoning health problem and is considered as a hepatic manifestation of metabolic syndrome. Increasing evidence demonstrates that berberine (BBR), a natural plant alkaloid, is beneficial for obesity-associated NAFLD. However, the mechanisms about how BBR improves hepatic steatosis remain uncertain. Recently, some reports revealed that enhanced autophagy could decrease hepatic lipid accumulation. In this study, we first established a high-fed diet (HFD) mice model and oleate–palmitate-induced lipotoxicity hepatocytes to explore the association among BBR, autophagy and hepatic steatosis. Our data demonstrated that BBR had profound effects on improving hepatic lipid accumulation bothin vivoandin vitro, and led to high autophagy flux. The molecular alterations proceeding these changes were characterized by inhibition of the ERK/mTOR pathway. These findings suggest an important mechanism for the positive effects of BBR on hepatic steatosis, and may provide new evidence for the clinical use of BBR in NAFLD.

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