scholarly journals Alleviating Effect of Quinoa and Underlying Mechanism on Hepatic Steatosis in High Fat Diet Fed Rat

2021 ◽  
Author(s):  
Chenwei Song ◽  
Wei Lv ◽  
Yahui Li ◽  
Pan Nie ◽  
Jun Lu ◽  
...  
Keyword(s):  
Immune Response ◽  
Lipid Metabolism ◽  
Fatty Liver ◽  
Hepatic Steatosis ◽  
Hepatic Tissue ◽  
Circulation System ◽  
Rna Seq ◽  
Rt Pcr ◽  
Alcoholic Fatty Liver ◽  
The Metabolic Syndrome

Abstract Background: HF diet-associated fatty liver (is also known as non-alcoholic fatty liver disease, NAFLD) is considered the hepatic component of the metabolic syndrome and has attracted widespread attention due to the increase in its prevalence. Daily dietary management, is considered to be one of the effective strategies for the prevention of NAFLD. In the present study, the effect of quinoa on the hepatic steatosis and the metabolism mechanism were investigated.Methods: Male SD rats simultaneously administered an HF diet and different amounts of quinoa (equivalent to 100 g/day and 300 g/day of human intake, respectively). After 12 weeks of the intervention, Hepatic TG and TC as well as serum anti-oxidative parameters were determined, H&E staining evaluated the hepatic steatosis. Differential metabolite in serum and hepatic tissue were analyzed using UPLC-QTOF-MSE. mRNA expression profile were investigated using RNA-Seq and further verified using real-time RT-PCR.Results: It showed that quinoa effectively controlled the weight of rats, mitigated hepatic steatosis and oxidative stress, which exhibited the beneficial effect of quinoa on prevention of NAFLD. These beneficial effects could be attributed to the regulation of the production of certain metabolites in the circulation system or liver such as LysoPC and PC. The RNA-Seq analysis and RT-PCR verification revealed that an intake of a high amount of quinoa more effectively up-regulated the genes related to lipid metabolism [Apoa (apolipoprotein)5, Apoa4, Apoc2) and down-regulated the genes related immune response [lrf (interferon regulatory factor)5, Tlr6 (Toll like receptor), Tlr10, Tlr11, Tlr12]. Conclusions: Quinoa could alleviate hepatic steatosis due to the regulation of metabolism and the expression of genes related with lipid metabolism and immune response.

scholarly journals Alleviating the effect of quinoa and the underlying mechanism on hepatic steatosis in high-fat diet-fed rats

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Chenwei Song ◽  
Wei Lv ◽  
Yahui Li ◽  
Pan Nie ◽  
Jun Lu ◽  
...  
Keyword(s):  
Immune Response ◽  
Lipid Metabolism ◽  
Hepatic Steatosis ◽  
High Fat Diet ◽  
Metabolic Profile ◽  
Hepatic Tissue ◽  
Circulation System ◽  
Rna Seq ◽  
Rt Pcr ◽  
High Fat

Abstract Background Nonalcoholic fatty liver disease (NAFLD) is considered the hepatic component of metabolic syndrome and has attracted widespread attention due to its increased prevalence. Daily dietary management is an effective strategy for the prevention of NAFLD. Quinoa, a nutritious pseudocereal, is abundant in antioxidative bioactive phytochemicals. In the present study, the effects of different amounts of quinoa on the progression of NAFLD and the related molecular mechanism were investigated. Methods Male SD rats were simultaneously administered a high fat diet (HF) and different amounts of quinoa (equivalent to 100 g/day and 300 g/day of human intake, respectively). After 12 weeks of the intervention, hepatic TG (triglyceride) and TC (total cholesterol) as well as serum antioxidative parameters were determined, and hematoxylin–eosin staining (H&E) staining was used to evaluate hepatic steatosis. Differential metabolites in serum and hepatic tissue were identified using UPLC-QTOF-MSE. The mRNA expression profile was investigated using RNA-Seq and further verified using real-time polymerase chain reaction (RT-PCR). Results Low amounts of quinoa (equivalent to 100 g/d of human intake) effectively controlled the weight of rats fed a high-fat diet. In addition, quinoa effectively inhibited the increase in hepatic TG and TC levels, mitigated pathological injury, promoted the increase in SOD and GSH-Px activities, and decreased MDA levels. Nontarget metabolic profile analysis showed that quinoa regulated lipid metabolites in the circulation system and liver such as LysoPC and PC. RNA-Seq and RT-PCR verification revealed that a high amount of quinoa more effectively upregulated genes related to lipid metabolism [Apoa (apolipoprotein)5, Apoa4, Apoc2] and downregulated genes related to the immune response [lrf (interferon regulatory factor)5, Tlr6 (Toll-like receptor), Tlr10, Tlr11, Tlr12]. Conclusion Quinoa effectively prevented NAFLD by controlling body weight, mitigating oxidative stress, and regulating the lipid metabolic profile and the expression of genes related to lipid metabolism and the immune response.

scholarly journals HEPATIC STEATOSIS IN SCHOOLCHILDREN AND ADOLESCENTS WITH CENTRAL OBESITY

2022 ◽  
Vol 7 (1) ◽  
pp. 32
Author(s):  
Tannia Jacqueline Lalaleo Portero ◽  
Carolina Arráiz de Fernández
Keyword(s):  
Physical Activity ◽  
Fatty Liver ◽  
Hepatic Steatosis ◽  
Central Obesity ◽  
Pediatric Population ◽  
Abdominal Ultrasound ◽  
Ultrasound Measurement ◽  
Cross Sectional ◽  
Alcoholic Fatty Liver ◽  
The Metabolic Syndrome

Introduction: Non-alcoholic hepatic steatosis is defined as the excessive accumulation of adipose tissue in the absence of alcohol consumption, being rare in the pediatric population. However, with the advent of the twentieth century pandemic, such as obesity, this pathology has increased its incidence, as well as others that belong to the metabolic syndrome. Objective: To determine the presence of hepatic steatosis in schoolchildren and adolescents with central obesity. Methods: observational, descriptive and cross-sectional research. The sample was of a census type, represented by 32 schoolchildren and adolescents who met the inclusion criteria, which are: age between 6 and 19 with central obesity - prior signing the informed consent. They underwent measurement of the waist circumference, abdominal ultrasound, measurement of the lipid profile and the determination of the level of physical activity through the application of the Pictorial Questionnaire of Infant Physical Activity. Results: 32 patients were studied, 18 (56.3%) male, adolescents 59.37%. With normal ultrasound (29/32) and with hepatic steatosis (3/32), of which 66.7% are grade II and 33.3% are grade III. Hypertriglyceridemia and borderline triglyceride levels 81.27% and hypercholesterolemia and borderline cholesterol levels 75%. Conclusion: School and adolescent patients with central obesity have borderline lipid profiles or dyslipidemia, in which, despite belonging to the pediatric population, moderate and severe cases of hepatic steatosis are evident. Keywords: fatty liver, non-alcoholic fatty liver disease, dyslipidemia, obesity.

scholarly journals Phosphorylation of eIF2α signaling pathway attenuates obesity-induced non-alcoholic fatty liver disease in an ER stress and autophagy-dependent manner

2020 ◽  
Vol 11 (12) ◽  
Author(s):  
Jie Li ◽  
Xinle Li ◽  
Daquan Liu ◽  
Shiqi Zhang ◽  
Nian Tan ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Liver Disease ◽  
Fatty Liver ◽  
Er Stress ◽  
Hepatic Steatosis ◽  
Fatty Liver Disease ◽  
Chow Diet ◽  
Dependent Manner ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

AbstractNon-alcoholic fatty liver disease (NAFLD) is the most common liver disorder and frequently exacerbates in postmenopausal women. In NAFLD, the endoplasmic reticulum (ER) plays an important role in lipid metabolism, in which salubrinal is a selective inhibitor of eIF2α de-phosphorylation in response to ER stress. To determine the potential mechanism of obesity-induced NAFLD, we employed salubrinal and evaluated the effect of ER stress and autophagy on lipid metabolism. Ninety-five female C57BL/6 mice were randomly divided into five groups: standard chow diet, high-fat (HF) diet, HF with salubrinal, HF with ovariectomy, and HF with ovariectomy and salubrinal. All mice except for SC were given HF diet. After the 8-week obesity induction, salubrinal was subcutaneously injected for the next 8 weeks. The expression of ER stress and autophagy markers was evaluated in vivo and in vitro. Compared to the normal mice, the serum lipid level and adipose tissue were increased in obese mice, while salubrinal attenuated obesity by blocking lipid disorder. Also, the histological severity of hepatic steatosis and fibrosis in the liver and lipidosis was suppressed in response to salubrinal. Furthermore, salubrinal inhibited ER stress by increasing the expression of p-eIF2α and ATF4 with a decrease in the level of CHOP. It promoted autophagy by increasing LC3II/I and inhibiting p62. Correlation analysis indicated that lipogenesis in the development of NAFLD was associated with ER stress. Collectively, we demonstrated that eIF2α played a key role in obesity-induced NAFLD, and salubrinal alleviated hepatic steatosis and lipid metabolism by altering ER stress and autophagy through eIF2α signaling.

scholarly journals CARF (CDKN2AIP) Regulates Hepatic Lipid Metabolism and Protects Against Development of Non-Alcoholic Fatty Liver Diseases

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A284-A284
Author(s):  
Kamrul M Hasan ◽  
Meher Parveen ◽  
Alondra Pena ◽  
Erick Galdamez Calles ◽  
Marvy Gergis ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Mouse Model ◽  
Fatty Liver ◽  
Hepatic Steatosis ◽  
Hepg2 Cells ◽  
Liver Diseases ◽  
Hepatic Lipid Metabolism ◽  
Alcoholic Fatty Liver ◽  
Hepatic Lipid

Abstract Non-alcoholic fatty liver diseases (NAFLD) is the most common form of liver diseases in the USA with 30–40% of American being affected and about 12% with nonalcoholic steatohepatitis (NASH), a leading cause of end-stage liver diseases. NAFLD has been linked with insulin resistance, type2 diabetes, obesity, and cardiovascular diseases but molecular mechanisms underlying the development of NAFLD and its association with metabolic syndromes are poorly understood. In this study, we explored the role of CARF (collaborator of ARF) also known as CDKN2AIP, a novel gene of ARF-MDM2-p53 pathway in the development of NAFLD. It has been shown that, p53, beyond its tumor suppressor functions, can regulate the cellular glucose and lipid metabolism and its activation has been reported to induce hepatic steatosis in mice. However, as a regulator of p53 pathway, the role of CARF in the lipid metabolism and associated metabolic diseases has not been studied yet. Using high-fat diet (HFD) fed obesity mouse model of NAFLD we found that the expression of CARF along with Sirt1, pAMPK, and pACC was significantly decreased in the HFD induced fatty livers compared to control. Similarly, CARF expression was also down-regulated in palmitate (PA)-treated HepG2 cells, an in vitro model of steatosis. We also observed that shRNA mediated knockdown or lentiviral vector mediated overexpression of CARF induced or reduced the endogenous fat accumulation, respectively, in HepG2 cells, suggesting that CARF expression is negatively regulated in NAFLD. Additionally, we performed RNA seq analysis after CARF silencing in HepG2 cells and demonstrated that silencing of CARF altered the expression of genes regulating hepatic de novo lipogenesis, beta-oxidation, and lipid secretion all of which favor the accumulation of fat in the hepatocytes. Furthermore, genes associated with mitochondrial functions such as the TCA cycle and oxidative phosphorylation were also altered which could play a role in the development of NAFLD. Finally, we demonstrated that AAV mediated hepatic overexpression of CARF in HFD fed mouse model significantly reduced the fat accumulation in the liver as evident by H&E staining of liver sections and intrahepatic triglyceride level. Altogether we conclude that CARF plays a vital role in hepatic lipid metabolism and its downregulation perturbs lipid homeostasis leading to hepatic steatosis and the development of NAFLD.

Healthy PNPLA3 Risk Allele Carriers Present with Unexpected Body Fat Composition. A Study of One ousand Subjects

2014 ◽  
Vol 23 (1) ◽  
pp. 33-37 ◽  
Author(s):  
Agnieszka Kempinska-Podhorodecka ◽  
Marcin Krawczyk ◽  
Marta Klak ◽  
Malgorzata Blatkiewicz ◽  
Frank Lammert ◽  
...  
Keyword(s):  
Body Weight ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Alcoholic Fatty Liver ◽  
The Metabolic Syndrome ◽  
Anthropometric Characteristics ◽  
The Common ◽  
Total Fat ◽  
Alcoholic Fatty Liver Disease

Introduction: The common PNPLA3 (adiponutrin) variant p.I148M represents a major genetic driver of progression in non-alcoholic fatty liver disease (NAFLD). NAFLD is commonly associated with traits of the metabolic syndrome, therefore it is mostly suspected in obese individuals. Here, we investigate the association between the PNPLA3 variant and anthropometric traits in a cohort of healthy individuals.Patients and methods: We recruited 1,000 (500 females; age 18 - 66 years) healthy blood donors. The PNPLA3 variant was genotyped using TaqMan assays. All individuals were phenotyped with respect to anthropometric characteristics. We also determined the percentage of total fat (F%) and active tissue (TA%) of body weight.Results: Healthy carriers of the PNPLA3 [IM] and [MM] genotypes, although not differing in height from individuals with the genotype [II], displayed significantly lower body weight and lower BMI (both P = 0.005), higher TA% (P = 0.03) but lower F% (P = 0.03) and smaller waist, chest and shin circumferences (all P < 0.05). Separate analysis for males and females demonstrated an association between the [IM] and [MM] genotypes and higher TA% but lower F% (P = 0.04) in females. In males, BMI and total weight were significantly (P = 0.04) lower among carriers of the [M] allele.Discussion: Healthy individuals carrying the prosteatotic PNPLA3 allele p.I48M may be leaner as compared to the carriers of the common allele. Hence in clinical practice they might be overlooked since they do not necessarily present with the anthropometric characteristics commonly associated with severe hepatic steatosis.Abbreviations: ATX - autotaxin; BMI - body mass index; F% - total fat of body weight in %; Fkg - total fat of body weight in kilograms; GWAS - genome-wide association study; LPA - lysophosphatidic acid; NAFLD, non-alcoholic fatty liver disease; NASH - non-alcoholic steatohepatitis; PA - phosphatidic acid; PNPLA3-patatin-like phospholipase domain containing 3 (adiponutrin); TA% - active tissue of body weight in %; TAkg - active tissue of body weight in kilograms; WHR - waist-to-hip ratio.

scholarly journals How does hepatic lipid accumulation lead to lipotoxicity in non-alcoholic fatty liver disease?

2021 ◽  
Vol 15 (1) ◽  
pp. 21-35
Author(s):  
Yana Geng ◽  
Klaas Nico Faber ◽  
Vincent E. de Meijer ◽  
Hans Blokzijl ◽  
Han Moshage
Keyword(s):  
Lipid Metabolism ◽  
Liver Disease ◽  
Fatty Liver ◽  
Lipid Accumulation ◽  
Fatty Liver Disease ◽  
Lipid Uptake ◽  
Cellular Mechanisms ◽  
Alcoholic Fatty Liver ◽  
Lipid Species ◽  
Alcoholic Fatty Liver Disease

Abstract Background Non-alcoholic fatty liver disease (NAFLD), characterized as excess lipid accumulation in the liver which is not due to alcohol use, has emerged as one of the major health problems around the world. The dysregulated lipid metabolism creates a lipotoxic environment which promotes the development of NAFLD, especially the progression from simple steatosis (NAFL) to non-alcoholic steatohepatitis (NASH). Purposeand Aim This review focuses on the mechanisms of lipid accumulation in the liver, with an emphasis on the metabolic fate of free fatty acids (FFAs) in NAFLD and presents an update on the relevant cellular processes/mechanisms that are involved in lipotoxicity. The changes in the levels of various lipid species that result from the imbalance between lipolysis/lipid uptake/lipogenesis and lipid oxidation/secretion can cause organellar dysfunction, e.g. ER stress, mitochondrial dysfunction, lysosomal dysfunction, JNK activation, secretion of extracellular vesicles (EVs) and aggravate (or be exacerbated by) hypoxia which ultimately lead to cell death. The aim of this review is to provide an overview of how abnormal lipid metabolism leads to lipotoxicity and the cellular mechanisms of lipotoxicity in the context of NAFLD.

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