• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.10 no.2
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• pp.185-192
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• 2007

Purpose: This study was conducted to evaluate the role of adiponectin, leptin, and tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) in the pathogenesis of non-alcoholic fatty liver disease (NAFLD) in obese children, and to elucidatethe relationship between these adipokines and insulin resistance. Methods: A total of 61 obese children (M : F=42 : 19, mean age 11.2${\pm}$1.3 years) admitted to our facility between March 2004 and June 2005 were included in this study. Patients were divided into three groups based on their NAFLD status obese children without fatty liver (N=23); obese children with simple steatosis (N=20); and obese children with non-alcoholic steatohepatitis (NASH) (N=18). The serum levels of adiponectin, leptin, and TNF-${\alpha}$ were measured, and insulin resistance determined by homeostasis model assessment (HOMA-IR) was calculated to estimate insulin resistance. In addition, the VSR (visceralsubcutaneous fat ratio) was estimated using abdominal computed tomography. Results: There was no difference in serum TNF-${\alpha}$ and leptin levels observed between the 3 groups (22.13${\pm}$6.37 vs. 21.35${\pm}$6.95 vs. 25.17${\pm}$9.30; p=0.342 & 20.29${\pm}$8.57 vs. 16.42${\pm}$6.85 vs. 20.10${\pm}$7.86; p=0.330). However, the serum adiponectin level was significantly lower in children with non-alcoholic steatohepatitis (NASH) than in the other two groups (6.08${\pm}$1.38 in children without steatosis vs. 5.69${\pm}$0.79 in simple steatosis vs. 4.93${\pm}$1.75 in NASH; p=0.026). In addition, the VSR was significantly increased in the NASH group (0.31${\pm}$0.08 vs. 0.32${\pm}$0.11 vs. 0.47${\pm}$0.14; p=0.001), and HOMA-IR revealed a significant difference among the three groups (4.77${\pm}$3.67 vs. 6.89${\pm}$7.05 vs. 10.42${\pm}$6.73; p=0.000). However, there was no significant correlation observed between the adiponectin levels and the HOMA-IR or the VSR (r=-0.117; p=0.450 & r=-0.106; p=0.499). Conclusion: Insulin resistance may affect the development of hepatic steatosis and steatohepatitis in children, and the results of this study suggest that, of several adipokines evaluated, adiponectin is important in the progression of steatosis to steatohepatitis in obese children.

• Journal of Life Science
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• v.32 no.12
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• pp.962-970
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• 2022

Nonalcoholic steatohepatitis (NASH) is the progressive stage of nonalcoholic fatty liver disease (NAFLD) that highly increases the risk of cirrhosis and liver cancer, and there are few therapeutic options available in the clinic. Poricoic acid (PoA), a component of Poria cocos Wolf, has a wide range of pharmacological activities; however, little is known about its effects on NASH. The preventive effects of PoA on NASH were examined in vivo and in vitro by analyzing triglyceride synthesis, inflammation and fibrosis. In the high fat and methionine-choline deficient diet (HFMCD)-induced NASH mice, PoA reduced the liver weight and the levels of alanine aminotransferase and aspartate aminotransferase compared with non-treated HFMCD group. The staining with Oil Red O and hematoxylin and eosin revealed that PoA administration reduced red staining and the size of lipid droplet. qPCR analysis showed that PoA also reduced the expression of genes related to triglyceride synthesis. Further, immunostaining with CD68 and qPCR analysis revealed that PoA reduced the staining with CD68 and the expression of inflammatory genes induced by HFMCD. Moreover, PoA reduced the staining with sirius red and antibody of α-smooth muscle actin and also reduced the expression of genes related to fibrosis. The treatment of PoA to AML12 cells reduced the increase in triglyceride amount and expression of genes associated with triglyceride synthesis, inflammation and fibrosis. Taken together, our study indicate that PoA has therapeutic effect on NASH through preventing triglyceride synthesis, inflammation and fibrosis.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.15 no.2
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• pp.74-78
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• 2012

With a markedly increased prevalence of obesity, non-alcoholic fatty liver disease (NAFLD) now becomes the most common cause of chronic liver disease in both adults and children. The etiology and pathogenesis of NAFLD are multifactorial and remain incompletely understood. According to the "two-hit" theory, inflammatory cytokines and adipokines are activated by oxidative stress and they are involved in insulin resistance, necroinflammatory steatohepatitis and fibrosis. This review discusses the latest updates on the role of some of important inflammatory adipokines and cytokines in the pathogenesis of NAFLD with an emphasis on their potential therapeutic implications.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.11 no.sup1
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• pp.149-152
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• 2008

Obesity tracks from childhood into adulthood, and the persistence of obesity rises with age among obese children. Obesity are independent risk factors for increased morbidity and mortality throughout the lifecycle. Obese individuals develop resistance to the cellular actions of insulin, characterized by an impaired ability of insulin to inhibit glucose output from the liver and to promote glucose uptake in fat and muscle. Insulin resistance is a key etiological factor for type 2 diabetes mellitus, dyslipidemia, hypertension, nonalcoholic steatohepatitis, polycystic ovarian syndrome.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.12 no.sup1
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• pp.62-71
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• 2009

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of pediatric liver disease. Similar to NAFLD in adults, NAFLD in children is associated with obesity and insulin resistance and requires liver histology for diagnosis and staging. However, significant histological differences exist between adult and pediatric NAFLD. The rise in childhood obesity has been accompanied by an increase in pediatric NAFLD. Age, gender and race/ethnicity are significant determinants of risk, and sex hormones, insulin sensitivity and adipocytokines are implicated in the pathogenesis of pediatric NAFLD. There is no consensus for treatment of NAFLD, however, data suggest that diet, exercise and some pharmacological therapies may be of benefit. To evaluate and effectively treat pediatric NAFLD, the pathophysiology and natural history of the disease should be clarified and non-invasive methods for screening, diagnosis, and longitudinal assessment developed.

• Clinical and Experimental Pediatrics
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• v.56 no.2
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• pp.45-51
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• 2013

Because nonalcoholic steatohepatitis can progress towards cirrhosis even in children, early detection of hepatic fibrosis and accurate diagnosis of nonalcoholic fatty liver disease (NAFLD) are important. Although liver biopsy is regarded as the gold standard of diagnosis, its clinical application is somewhat limited in children due to its invasiveness. Noninvasive diagnostic methods, including imaging studies, biomarkers of inflammation, oxidative stress, hepatic apoptosis, hepatic fibrosis, and noninvasive hepatic fibrosis scores have recently been developed for diagnosing the spectrum of NAFLD, particularly the severity of hepatic fibrosis. Although data and validation are still lacking for these noninvasive modalities in the pediatric population, these methods may be applicable for pediatric NAFLD. Therefore, noninvasive imaging studies, biomarkers, and hepatic fibrosis scoring systems may be useful in the detection of hepatic steatosis and the prediction of hepatic fibrosis, even in children with NAFLD.

• BMB Reports
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• v.42 no.8
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• pp.475-481
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• 2009

Emerging data demonstrate pivotal roles for brain insulin resistance and insulin deficiency as mediators of cognitive impairment and neurodegeneration, particularly Alzheimer's disease (AD). Insulin and insulin-like growth factors (IGFs) regulate neuronal survival, energy metabolism, and plasticity, which are required for learning and memory. Hence, endogenous brain-specific impairments in insulin and IGF signaling account for the majority of AD-associated abnormalities. However, a second major mechanism of cognitive impairment has been linked to obesity and Type 2 diabetes (T2DM). Human and experimental animal studies revealed that neurodegeneration associated with peripheral insulin resistance is likely effectuated via a liver-brain axis whereby toxic lipids, including ceramides, cross the blood brain barrier and cause brain insulin resistance, oxidative stress, neuro-inflammation, and cell death. In essence, there are dual mechanisms of brain insulin resistance leading to AD-type neurodegeneration: one mediated by endogenous, CNS factors; and the other, peripheral insulin resistance with excess cytotoxic ceramide production.

• Journal of Ginseng Research
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• v.42 no.3
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• pp.352-355
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• 2018

In this study, we precisely showed how the Rg3-enriched red ginseng extract (Rg3-RGE) lowers glucose, triglyceride, and low-density lipoprotein (LDL) levels in $LDL^{-/-}$ mice. Aspartate aminotransferase/serum glutamic-oxaloacetic transaminase), alanine aminotransferase /serum glutamate-pyruvate transaminase, and steatohepatitis were found to be reduced, and atheroma formation was inhibited by Rg3-enriched red ginseng extract.

• BMB Reports
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• v.55 no.10
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• pp.481-487
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• 2022

Over the past few years, hydrogen sulfide (H₂S) has been shown to exert several biological functions in mammalian. The endogenous production of H₂S is mainly mediated by cystathione β-synthase, cystathione γ-lyase and 3-mercaptopyruvate sulfur transferase. These enzymes are broadly expressed in liver tissue and regulates liver function by working on a variety of molecular targets. As an important regulator of liver function, H₂S is critically involved in the pathogenesis of various liver diseases, such as non-alcoholic steatohepatitis and liver cancer. Targeting H₂S-generating enzymes may be a therapeutic strategy for controlling liver diseases. This review described the function of H₂S in liver disease and summarized recent characterized role of H₂S in several cellular process of the liver.

• The Korean Journal of Physiology and Pharmacology
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• v.27 no.4
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• pp.299-310
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• 2023

Non-alcoholic fatty liver disease (NAFLD) is a complex disorder characterized by the accumulation of fat in the liver in the absence of excessive alcohol consumption. It is one of the most common liver diseases worldwide, affecting approximately 25% of the global population. It is closely associated with obesity, type 2 diabetes, and metabolic syndrome. Moreover, NAFLD can progress to non-alcoholic steatohepatitis, which can cause liver cirrhosis, liver failure, and hepatocellular carcinoma. Currently, there are no approved drugs for the treatment of NAFLD. Therefore, the development of effective drugs is essential for NAFLD treatment. In this article, we discuss the experimental models and novel therapeutic targets for NAFLD. Additionally, we propose new strategies for the development of drugs for NAFLD.