scholarly journals Momordica cochinchinensis Aril Ameliorates Diet-Induced Metabolic Dysfunction and Non-Alcoholic Fatty Liver by Modulating Gut Microbiota

2021 ◽  
Vol 22 (5) ◽  
pp. 2640
Author(s):  
Hsiu-Chen Huang ◽  
Chiung-Ju Chen ◽  
Yu-Heng Lai ◽  
Yu-Chun Lin ◽  
Wei-Chung Chiou ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Cell Model ◽  
Body Weight Gain ◽  
Peroxisome Proliferator ◽  
Alcoholic Fatty Liver ◽  
Nonalcoholic Fatty Liver ◽  
Momordica Cochinchinensis

Obesity and its associated conditions, such as type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD), are a particular worldwide health problem at present. Momordica cochinchinensis (MC) is consumed widely in Southeast Asia. However, whether it has functional effects on fat-induced metabolic syndrome remains unclear. This study was conducted to examine the prevention effect of Momordica cochinchinensis aril (MCA) on obesity, non-alcoholic fatty liver and insulin resistance in mice. MCA protected the mice against high-fat diet (HFD)-induced body weight gain, hyperlipidemia and hyperglycemia, compared with mice that were not treated. MCA inhibited the expansion of adipose tissue and adipocyte hypertrophy. In addition, the insulin sensitivity-associated index that evaluates insulin function was also significantly restored. MCA also regulated the secretion of adipokines in HFD-induced obese mice. Moreover, hepatic fat accumulation and liver damage were reduced, which suggested that fatty liver was prevented by MCA. Furthermore, MCA supplementation suppressed hepatic lipid accumulation by activation of the AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor-alpha (PPAR-alpha) signaling pathway in the human fatty liver HuS-E/2 cell model. Our data indicate that MCA altered the microbial contents of the gut and modulated microbial dysbiosis in the host, and consequently is involved in the prevention of HFD-induced adiposity, insulin resistance and non-alcoholic fatty liver disease.

Natural Aldose Reductase Inhibitor: A Potential Therapeutic Agent for Non-alcoholic Fatty Liver Disease

2020 ◽  
Vol 21 (6) ◽  
pp. 599-609 ◽  
Author(s):  
Longxin Qiu ◽  
Chang Guo
Keyword(s):  
Oxidative Stress ◽  
Liver Disease ◽  
Fatty Liver ◽  
Aldose Reductase ◽  
Fatty Liver Disease ◽  
Acid Oxidation ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Alcoholic Fatty Liver ◽  
Nonalcoholic Fatty Liver

Aldose reductase (AR) has been reported to be involved in the development of nonalcoholic fatty liver disease (NAFLD). Hepatic AR is induced under hyperglycemia condition and converts excess glucose to lipogenic fructose, which contributes in part to the accumulation of fat in the liver cells of diabetes rodents. In addition, the hyperglycemia-induced AR or nutrition-induced AR causes suppression of the transcriptional activity of peroxisome proliferator-activated receptor (PPAR) α and reduced lipolysis in the liver, which also contribute to the development of NAFLD. Moreover, AR induction in non-alcoholic steatohepatitis (NASH) may aggravate oxidative stress and the expression of inflammatory cytokines in the liver. Here, we summarize the knowledge on AR inhibitors of plant origin and review the effect of some plant-derived AR inhibitors on NAFLD/NASH in rodents. Natural AR inhibitors may improve NAFLD at least in part through attenuating oxidative stress and inflammatory cytokine expression. Some of the natural AR inhibitors have been reported to attenuate hepatic steatosis through the regulation of PPARα-mediated fatty acid oxidation. In this review, we propose that the natural AR inhibitors are potential therapeutic agents for NAFLD.

scholarly journals RIPK3 acts as a lipid metabolism regulator contributing to inflammation and carcinogenesis in non-alcoholic fatty liver disease

Gut ◽  
2020 ◽  
pp. gutjnl-2020-321767
Author(s):  
Marta B Afonso ◽  
Pedro M Rodrigues ◽  
Miguel Mateus-Pinheiro ◽  
André L Simão ◽  
Maria M Gaspar ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Body Weight Gain ◽  
Control Diet ◽  
Peroxisome Proliferator ◽  
Functional Link ◽  
Alcoholic Fatty Liver ◽  
The Impact ◽  
Alcoholic Fatty Liver Disease

ObjectiveReceptor-interacting protein kinase 3 (RIPK3) is a key player in necroptosis execution and an emerging metabolic regulator, whose contribution to non-alcoholic fatty liver disease (NAFLD) is controversial. We aimed to clarify the impact of RIPK3 signalling in the pathogenesis of human and experimental NAFLD.DesignRIPK3 levels were evaluated in two large independent cohorts of patients with biopsy proven NAFLD diagnosis and correlated with clinical and biochemical parameters. Wild-type (WT) or Ripk3-deficient (Ripk3−/−) mice were fed a choline-deficient L-amino acid-defined diet (CDAA) or an isocaloric control diet for 32 and 66 weeks.ResultsRIPK3 increased in patients with non-alcoholic steatohepatitis (NASH) in both cohorts, correlating with hepatic inflammation and fibrosis. Accordingly, Ripk3 deficiency ameliorated CDAA-induced inflammation and fibrosis in mice at both 32 and 66 weeks. WT mice on the CDAA diet for 66 weeks developed preneoplastic nodules and displayed increased hepatocellular proliferation, which were reduced in Ripk3−/− mice. Furthermore, Ripk3 deficiency hampered tumourigenesis. Intriguingly, Ripk3−/− mice displayed increased body weight gain, while lipidomics showed that deletion of Ripk3 shifted hepatic lipid profiles. Peroxisome proliferator-activated receptor γ (PPARγ) was increased in Ripk3−/− mice and negatively correlated with hepatic RIPK3 in patients with NAFLD. Mechanistic studies established a functional link between RIPK3 and PPARγ in controlling fat deposition and fibrosis.ConclusionHepatic RIPK3 correlates with NAFLD severity in humans and mice, playing a key role in managing liver metabolism, damage, inflammation, fibrosis and carcinogenesis. Targeting RIPK3 and its intricate signalling arises as a novel promising approach to treat NASH and arrest disease progression.

scholarly journals Role of the endocrine system in the pathogenesis of non-alcoholic fatty liver disease

2009 ◽  
Vol 150 (48) ◽  
pp. 2173-2181 ◽  
Author(s):  
Krisztina Hagymási ◽  
Péter Reismann ◽  
Károly Rácz ◽  
Zsolt Tulassay
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Endocrine System ◽  
Hormone Deficiency ◽  
Alcoholic Fatty Liver ◽  
Nonalcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

The most frequent liver disorder in metabolic syndrome is the nonalcoholic fatty liver disease. Its pathogenesis is a complex, multifactorial process, characterized by insulin resistance and involvement of the endocrine system. Hypothyroidism may lead to nonalcoholic steatohepatitis via hyperlipidemia and obesity. Adult patients with growth hormone deficiency have a metabolic syndrome-like phenotype with obesity and many characteristic metabolic alterations. The chronic activation of the hypothalamic-pituitary-adrenal axis results in metabolic syndrome as well. Cushing’s syndrome has also features of metabolic syndrome. Mild elevation of transaminase activities is commonly seen in patients with adrenal failure. Non-alcoholic steatosis is twice as common in postmenopusal as in premenopausal women and hormonal replacement therapy decreases the risk of steatosis. Insulin resistance, diabetes mellitus type 2, sleeping apnoe syndrome, cardiovascular disorders and non-alcoholic fatty liver disease are more frequent in polycystic ovary syndrome. Hypoandrogenism in males and hyperandrogenism in females may lead to fatty liver via obesity and insulin resistance. Adipokines (leptin, acylation stimulating protein, adiponectin) have a potential role in the pathogenesis of nonalcoholic fatty liver. The alterations of endocrine system must be considered in the background of cryptogenic liver diseases. The endocrine perspective may help the therapeutic approaches in the future.

scholarly journals Hepatic Mitochondrial Remodeling is Mechanistically Linked to Insulin Resistance in Nonalcoholic Fatty Liver Disease

2020 ◽  
Author(s):  
Chris E. Shannon ◽  
Mukundan Ragavan ◽  
Juan Pablo Palavicini ◽  
Marcel Fourcaudot ◽  
Terry Bakewell ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Liver Disease ◽  
Fatty Liver ◽  
Mitochondrial Function ◽  
Fatty Liver Disease ◽  
Tca Cycle ◽  
Alcoholic Fatty Liver ◽  
Nonalcoholic Fatty Liver ◽  
Insulin Resistant ◽  
Mitochondrial Remodeling

ABSTRACTInsulin resistance and altered hepatic mitochondrial function are central features of type 2 diabetes (T2D) and non-alcoholic fatty liver disease (NAFLD), but the etiological role of these processes in disease progression remains unclear. We investigated the molecular links between insulin resistance, mitochondrial remodeling, and hepatic lipid accumulation in a rodent model of T2D / NAFLD. Livers from obese, insulin resistant mice displayed augmented mitochondrial content and increased TCA cycle and pyruvate dehydrogenase (PDH) activities. Insulin sensitization with pioglitazone mitigated pyruvate-driven TCA cycle activity and PDH activation via both covalent (PDK4 and PDP2) and allosteric (intracellular pyruvate availability) mechanisms. Interestingly, improvements in insulin sensitivity and mitochondrial function were entirely dissociated from changes in hepatic triglycerides, diacylglycerides or fatty acids. Instead, we show that the mitochondrial phospholipid cardiolipin undergoes pathological remodeling in livers from obese mice and that this is reversed by insulin sensitization. Our findings identify targetable mitochondrial features of T2D and NAFLD and highlight the benefit of insulin sensitization in managing the clinical burden of obesity-associated disease.

scholarly journals Non Alcoholic Fatty Liver Disease- Is it a Rarity in Children of Bangladesh?

2020 ◽  
Vol 44 (2) ◽  
pp. 97-103
Author(s):  
ASM Bazlul Karim ◽  
Md Rukunuzzaman
Keyword(s):  
Insulin Resistance ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Elevated Serum ◽  
Physical Activities ◽  
Screening Tests ◽  
Alcoholic Fatty Liver ◽  
Nonalcoholic Fatty Liver ◽  
Serum Aminotransferases

Nonalcoholic fatty liver disease (NAFLD) is a disease of liver occurring due to excess accumulation of fat in the liver. For defining NAFLD, there must be evidence of hepatic steatosis (HS), either by imaging or by histology and lack of secondary causes of hepatic fat accumulation. Frequency of NAFLD is increasing worldwide. Overall prevalence of NAFLD in Bangladesh is 33.9%. Insulin resistance is the central factor for the pathogenesis of NAFLD. Most of the children are asymptomatic and are identified incidentally by elevated serum aminotransferases. The objectives of this review are to provide the pediatricians an overview of fatty liver disease in children regarding its etiology, patients’ evaluation and management. This review also provides the approach to a child with fatty liver disease based on the best available evidence from electronic literature searches. Obese (BMI for age > 95th centile) and overweight children (BMI for age between 85th to 95th centile) having additional risk factors like insulin resistance should be routinely screened for NAFLD. Estimation of serum ALT and/ or ultrasonography are the recommended screening tests. Though the treatment of NAFLD includes dietary modifications, physical activities, drugs and surgery; diet and physical activities are the cornerstone of management of NAFLD. Bangladesh J Child Health 2020; VOL 44 (2) :97-103

scholarly journals Biomarkers in Nonalcoholic Fatty Liver Disease

2014 ◽  
Vol 28 (11) ◽  
pp. 607-618 ◽  
Author(s):  
Manuela G Neuman ◽  
Lawrence B Cohen ◽  
Radu M Nanau
Keyword(s):  
Insulin Resistance ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Apolipoprotein A1 ◽  
Specific Reference ◽  
Disease Manifestation ◽  
Alcoholic Fatty Liver ◽  
Nonalcoholic Fatty Liver

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a chronic liver condition characterized by insulin resistance, type 2 diabetes and fat accumulation in the liver that may cause hepatic inflammation and progressive scarring leading to nonalcoholic steatohepatitis (NASH) and irreversible liver damage (cirrhosis). As a result, there has been increased recognition of the need to assess and closely monitor individuals for risk factors of components of NAFLD and NASH, as well as the severity of these conditions using biomarkers.AIM: To review the biomarkers used to diagnose and define the severity of NAFLD and NASH.METHODS: A comprehensive PubMed and Google Scholar literature search was performed using the terms “non-alcoholic fatty liver disease”, “non-alcoholic steatohepatitis”, as well as the name of each biomarker known to be used. Articles indexed between 2004 and 2014 were used. Each author read the publications separately and the results were discussed.RESULTS: Biomarkers offer a potential prognostic or diagnostic indicator for disease manifestation, progression or both. Serum biomarkers, including total cholesterol, triglycerides, insulin resistance and C-peptide, have been used for many years. Emerging biomarkers, such as apolipoprotein A1, apolipoprotein B, leptin, adiponectin, free fatty acids, ghrelin and tumour necrosis factor-alpha, have been proposed as tools that could provide valuable complementary information to that obtained from traditional biomarkers. Moreover, markers of cell death and mitochondrial dysfunction (cytokeratins) represent powerful predictors of risk. For biomarkers to be clinically useful in accurately diagnosing and treating disorders, age-specific reference intervals that account for differences in sex and ethnic origin are a necessity.CONCLUSIONS: The present review attempts to provide a comprehensive analysis of the emerging risk biomarkers of NAFLD and NASH, and to use the clinical significance and analytical considerations of each biomarker pointing out sentinel features of disease progression.

scholarly journals Non Alcoholic Fatty Liver Disease- Is It Always Benign?

1970 ◽  
Vol 25 (3) ◽  
pp. 144-152 ◽  
Author(s):  
Mohammad Mohibur Rahman ◽  
Tariq Abedin ◽  
Robed Amin ◽  
M Ridwanur Rahman ◽  
Md Abul Faiz
Keyword(s):  
Insulin Resistance ◽  
Liver Disease ◽  
Liver Biopsy ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Asian Population ◽  
Imaging Method ◽  
Alcoholic Fatty Liver ◽  
Nonalcoholic Fatty Liver ◽  
The Metabolic Syndrome

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease observed in the clinical practice of hepatology affecting approximately 20% of the general population. It is increasingly apparent that non alcoholic steatohepatits (NASH) and NAFLD are not Western disease. There is evolution of Western-style life among the Asian population and NASH has increasingly been diagnosed in several regions in Asia. NASH is considered as a type of a larger spectrum of NAFLD that is a consequence of insulin resistance and other underlying factors with histological findings ranging from fatty change alone to fat plus inflammation, to fat plus ballooning degeneration, and to fat plus alcoholic hepatitis-like lesions including Mallory body and fibrosis, the latter two categories being considered as NASH. Although liver biopsy is currently the gold standard for diagnosis, there is a need for less invasive methods. Imaging by ultrasound, computerized tomography and magnetic resonance are all able to demonstrate fat. Ultrasound, although probably not the most reliable imaging method, has many advantages and, when positive, gives a high degree of certainty of the diagnosis depending on the prevalence of fatty liver in the population being studied. Unlike liver biopsy, none of these techniques is able to differentiate simple steatosis from non- alcoholic steatohepatitis. The ultimate goal of treating the patient with NASH is to prolong life by avoiding the end-organ diseases associated with insulin resistance and the metabolic syndrome. Treatment of patients with nonalcoholic fatty liver has typically been focused on the management of associated conditions as well as discontinuation of potentially hepatotoxic drugs. Weight loss and exercise improve insulin sensitivity. Bariatric surgery may improve liver histology in patients with morbid obesity. Insulin sensitising drugs showed promise in pilot trials as have a number of hepatoprotective agents. Further randomised, well controlled trials are required to determine the efficacy of these drugs. In this article, we will review (1) various processes that are involved in the pathogenesis of NASH (2) the existing medical therapy for patients with nonalcoholic fatty liver, (2) the emerging and potentially useful medications. (J Bangladesh Coll Phys Surg 2007; 25 : 144-152)

scholarly journals Nonalcoholic Fatty Liver Disease (NAFLD) - A Disease of New Era

1970 ◽  
Vol 8 (1) ◽  
pp. 17-27
Author(s):  
Md Abul Kalam Azad ◽  
Shaheen Lipika Quayum ◽  
Hanif Mohammad ◽  
Maj Chowdhury ◽  
Tak Mahmood ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Oxidant Stress ◽  
Bacterial Overgrowth ◽  
Hepatocellular Injury ◽  
Alcoholic Fatty Liver ◽  
Nonalcoholic Fatty Liver ◽  
The Metabolic Syndrome

Non-alcoholic fatty liver disease (NAFLD) is the term used to describe the alcohol-like liver injury that occurs in the absence of alcohol abuse (alcohol consumption of over 20 g/day excludes the condition). It includes a range of histological abnormalities including simple steatosis or fatty liver, non-alcoholic steatohepatitis (NASH) and NAFLD induced cirrhosis. Its increasing prevalence in western countries, the diagnostic difficulties by noninvasive tests, and the possibility of progression to advanced fibrosis and even cirrhosis make NASH a challenge for physicians. NASH is frequently associated with type 2 diabetes and the metabolic syndrome, and several genetic and acquired factors are involved in its pathogenesis. Insulin resistance plays a central role in the development of a steatotic liver, which becomes vulnerable to additional injuries. Several cyclic mechanisms leading to self-enhancement of insulin resistance and hepatic accumulation of fat have been recently identified. Excess intracellular fatty acids, oxidant stress, tumor necrosis factor, and mitochondrial dysfunction are causes of hepatocellular injury, thereby leading to disease progression and to the establishment of NASH. Intestinal bacterial overgrowth also plays a role, by increasing production of endogenous ethanol and proinflammatory cytokines. Therapeutic strategies aimed at modulating insulin resistance, managing risk factors, including reduction of weight normalizing lipoprotein metabolism, and down regulating inflammatory mediators with probiotics have promising potential.   DOI = 10.3329/jom.v8i1.1375 J MEDICINE 2007; 8 : 17-27

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