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Nonalcoholic hepatic steatosis

Miaoting Yang, Zhijuan Chen, Chunxin Xiao, Waijiao Tang, Beijie Zhou
OBJECTIVE: To investigate the effects of sera from rats fed with Huganqingzhi tablets (HGT) on endoplasmic reticulum (ER) stress in a steatotic hepatocyte model of free fatty acids (FFAs)-induced nonalcoholic fatty liver disease (NAFLD) and explore the possible mechanism. METHODS: FFAs prepared by mixing oleic acid and palmitic acid at the ratio of 2:1. HepG2 cells were treated with the sera from rats fed with low-, moderate-or high-dose HGT (HGT sera) or sera of rats fed with fenofibrate (fenofibrate sera), followed by treatment with 1 mmol/L FFAs for 24 h to induce hepatic steatosis...
November 30, 2018: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
Nathan C Winn, Thomas J Jurrissen, Zachary I Grunewald, Rory P Cunningham, Makenzie L Woodford, Jill A Kanaley, Dennis B Lubahn, Camila Manrique-Acevedo, R Scott Rector, Victoria J Vieira-Potter, Jaume Padilla
The role of estrogen receptor alpha (ERα) signaling in immunometabolic function is established in females. However, its necessity in males, while appreciated, requires further study. Accordingly, we first determined whether lower metabolic function in male mice compared to females is related to reduced ERα expression. ERα protein expression in metabolically active tissues was lower in males than females and this lower expression was associated with worse glucose tolerance. Second, we determined if ERα is required for optimal immunometabolic function in male mice consuming chow diet...
December 4, 2018: American Journal of Physiology. Endocrinology and Metabolism
Benjamin Kramer, Lucas Martins França, Youhua Zhang, Antonio Marcus de Andrade Paes, A Martin Gerdes, Maria Alicia Carrillo-Sepulveda
Overconsumption of a diet rich in fat and carbohydrates, called the Western diet, is a major contributor to the global epidemic of cardiovascular disease. Despite previously documented cardiovascular protection exhibited in female rats, this safeguard may be lost under certain metabolic stressors. We hypothesized that female Wistar rats challenged by a Western diet composed of 21% fat and 50% carbohydrate (34.1% sucrose) for 17 wk would develop endothelial dysfunction via endothelial Toll-like receptor 4 (TLR4) signaling...
December 1, 2018: American Journal of Physiology. Heart and Circulatory Physiology
Guy Rostoker, Christelle Loridon, Mireille Griuncelli, Clémentine Rabaté, Fanny Lepeytre, Pablo Ureña-Torres, Belkacem Issad, Nasredine Ghali, Yves Cohen
BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a spectrum of diseases including steatosis, nonalcoholic steatohepatitis (NASH), cirrhosis, and end-stage liver failure. Hepatic iron accumulation has been linked to hepatic fibrosis severity in NASH and NAFLD. Iron overload induced by parenteral (IV) iron therapy is a potential clinical problem in dialysis patients. We analyzed the hypothetical triggering and aggravating role of iron on NAFLD in patients on dialysis. METHODS: Liver iron concentration (LIC) and hepatic proton density fat fraction (PDFF) were analyzed prospectively in 68 dialysis patients by magnetic resonance imaging (MRI)...
November 27, 2018: EBioMedicine
Eduardo J Arista Romeu, Galileo Escobedo, Adriana Campos-Espinosa, Ivette Irais Romero-Bello, Javier Moreno-González, Diego A Fabila-Bustos, Alma Valor Reed, Suren Stolik Isakina, José Manuel de la Rosa Vázquez, Carolina Guzmán
Nonalcoholic fatty liver disease (NAFLD) ranges from steatosis to nonalcoholic steatohepatitis and cirrhosis. Liver biopsy, considered the gold standard to diagnose NAFLD, shows significantly high rates of interobserver variability. Thus there is a need to develop tools that accurately categorize mild and advanced grades of steatosis in order to identify patients at higher risk of developing chronic liver disease. Diffuse reflectance spectroscopy (DRS) has proved to be useful in grading liver fibrosis and cirrhosis, without having been implemented for steatosis...
November 2018: Journal of Biomedical Optics
Maoru Li, Ji Ma, Owais Ahmad, Yi Cao, Bing Wang, Qiangqiang He, Jiajing Li, Hongli Yin, Yifan Zhang, Jiang He, Jing Shang
Nonalcoholic fatty liver disease (NAFLD)1 is the most common chronic liver disease worldwide. Cichorium glandulosum Huet (CG) is a common traditional Uighur medicine, and it has been widely used as active therapy on various hepatic diseases. Recently, lipid-lowering effect has been revealed on CG. Polysaccharides are principal component of CG which could be the possible lipid-lowering compound in CG. In this study, extraction and purification of CG polysaccharides (CGP) was performed, and the lipid regulation effect of CGP was investigated on NAFLD zebrafish model...
October 2, 2018: Journal of Pharmacological Sciences
Yoosoo Chang, Yoo-Hun Noh, Byung-Seong Suh, Yejin Kim, Eunju Sung, Hyun-Suk Jung, Chan-Won Kim, Min-Jung Kwon, Kyung Eun Yun, Jin-Won Noh, Hocheol Shin, Yong Kyun Cho, Seungho Ryu
Nonalcoholic fatty liver disease (NAFLD) and gallstone disease (GD) are often found to coexist but the sequential relationship of NAFLD and GD to each other remains controversial. We prospectively evaluated the bidirectional relationship of NAFLD with GD. A cohort study was performed on Korean adults who underwent a health checkup and were followed annually or biennially for a mean of 6.0 years. Fatty liver and gallstones were diagnosed by ultrasound. NAFLD was defined as hepatic steatosis on ultrasonography in the absence of excessive alcohol use or other identifiable causes...
November 21, 2018: Journal of Clinical Medicine
Tomomi Yamada, Yuto Kashiwagi, Takemi Rokugawa, Hideaki Kato, Haruyo Konishi, Tadateru Hamada, Ryohei Nagai, Yusaku Masago, Michiko Itoh, Takayoshi Suganami, Yoshihiro Ogawa, Kohji Abe
INTRODUCTION: Melanocortin 4 receptor-deficient (MC4R-KO) mice fed a high-fat diet (HFD) develop liver pathology similar to human nonalcoholic steatohepatitis (NASH). However, although liver histology and blood biochemistry have been reported, hepatic function has not been evaluated. In the present study, we evaluated hepatic function in MC4R-KO mice fed an HFD using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) with gadolinium‑ethoxybenzyl‑diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)...
November 19, 2018: Magnetic Resonance Imaging
Kai-Pi Cheng, Horng-Yih Ou, Hao-Chang Hung, Chung-Hao Li, Kang-Chih Fan, Jin-Shang Wu, Hung-Tsung Wu, Chih-Jen Chang
Hepassocin (HPS) is a hepatokine that regulates hepatocyte proliferation. It is known that HPS plays an important role in the development of nonalcoholic fatty liver diseases (NAFLD). Fatty acids, such as oleic acid (OLA), exhibit the ability to activate the signal transducer and activator of transcription-3 (STAT3), and the binding site of STAT3 is found in the promoter region of HPS. However, the regulation of HPS by fatty acids is still obscure. To clarify the regulation of HPS, we detected the expression of HPS by western blots...
September 2018: Lipids
Xiaobo Gao, Shun Guo, Song Zhang, An Liu, Lei Shi, Yan Zhang
BACKGROUND: Endoplasmic reticulum (ER) stress, which can promote lipid metabolism disorders and steatohepatitis, contributes significantly to the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Calcium (Ca2+ ) homeostasis is considered to play a key role in ER stress. Matrine (Mat) has been applied for the treatment of hepatitis B, but its effect on NAFLD is still unknown, and there is no unified view of Mat on the regulation of ER stress in the previous literature. METHODS: The pharmacological effects were studied in high-fat-diet or methionine-choline-deficient diet induced C57BL/6J mice models and in palmitic acid (PA) induced L02 human liver cell model...
November 20, 2018: Journal of Translational Medicine
Shigeki Masuda, Yuya Fujishima, Norikazu Maeda, Yuri Tsugawa-Shimizu, Yuto Nakamura, Yoshimitsu Tanaka, Yoshinari Obata, Shiro Fukuda, Hirofumi Nagao, Shunbun Kita, Hitoshi Nishizawa, Iichiro Shimomura
Glycosylphosphatidylinositol-specific phospholipase D (GPI-PLD) is an enzyme which specifically cleaves GPI anchors. Previous human studies suggested the relationship of GPI-PLD to insulin resistance, Type 1 and type 2 diabetes, and nonalcoholic fatty liver disease (NAFLD). However, the biological roles of GPI-PLD have not been elucidated. Here, we hypothesized that GPI-PLD impacted on lipid and glucose metabolism, especially in liver. GPI-PLD mRNA was most highly expressed in liver, and hepatic mRNA level and circulating concentration of GPI-PLD were significantly augmented in diabetic mice...
November 20, 2018: American Journal of Physiology. Endocrinology and Metabolism
Huiling Jiang, Qiaowei Guan, Yewei Xiao, Zhiqiang Feng, Guang Yu, Qiangwen Pan
The purpose of this study was to explore the effects of strontium on fatty liver, and to clarify the possible mechanisms by which strontium improves nonalcoholic fatty liver disease (NAFLD). We also evaluated how strontium affected the endoplasmic reticulum stress (ERS) pathways. We established an in vitro model of NAFLD using a human hepatocyte cell line (L02) treated with 0.2 mM palmitic acid. The Sprague-Dawley rats were fed with a high-fat diet (HFD) to establish NAFLD model in vivo. After strontium treatment, the total cholesterol (TC), triglyceride (TG), and lipid deposition in L02 cells and liver tissues were determined...
November 17, 2018: Journal of Medicinal Food
Jing Luo, Qian Chen, Tianran Shen, Xu Wang, Wanjun Fang, Xiaocai Wu, Zenan Yuan, Gengdong Chen, Wenhua Ling, Yuming Chen
Background: Sex hormone-binding globulin (SHBG), a glycoprotein synthesized by hepatocytes, has been linked to insulin resistance and hepatic lipid metabolism and is suggested to be associated with nonalcoholic fatty liver disease (NAFLD). This study aimed to investigate the association of SHBG with NAFLD in Chinese adults. Methods: We conducted a community-based, cross-sectional study in China involving 2912 participants aged 40-75 years old. All participants underwent detection for hepatic fat infiltration by ultrasound in addition to providing complete medical history and undergoing physical and blood biochemical examinations...
2018: Nutrition & Metabolism
Qiuyue Kong, Nan Li, Hao Cheng, Xiaojin Zhang, Xiaofei Cao, Tao Qi, Leyang Dai, Zhihong Zhang, Xuan Chen, Chuanfu Li, Yuehua Li, Bin Xue, Lei Fang, Li Liu, Zhengnian Ding
Nonalcoholic steatohepatitis (NASH) is the most prevalent cause of chronic liver disease worldwide. Macrophage-mediated inflammation plays a critical role in NASH pathogenesis; however, optimum therapies for macrophage activation and NASH remain elusive. Heat shock protein 12A (HSPA12A) encodes a novel member of the HSP70 family. Here, we report that NASH patients showed increased hepatic HSPA12A expression and serum HSPA12A contents. Intriguingly, knockout of HSPA12A ( Hspa12a -/- ) in mice attenuated high-fat diet (HFD)-induced hepatic steatosis and injury...
November 19, 2018: Diabetes
Chen Li, Qing Liu, Liqun Xie
Nonalcoholic fatty liver disease (NAFLD) is characterized by lipid accumulation and inflammation in the liver, contributing to a broad spectrum of severe pathologies, such as metabolic syndrome and hepatocellular carcinoma. Presently, the pathogenesis that attributes to NAFLD has not been fully understood. NLRP2 has been shown to inhibit the NF-κB signaling, and thus may contribute to regulate the inflammatory response. However, its role in NAFLD is largely unclear. In the study, we found that NLRP2 was markedly decreased in liver tissues of individuals with severe steatosis, or in a genetic deficiency (ob/ob) mice...
December 9, 2018: Biochemical and Biophysical Research Communications
Vinay Sundaram, Timothy R Morgan
Hepatic steatosis and steatohepatitis have several etiologies; the most common are alcoholic steatohepatitis (ASH) and obesity/metabolic syndrome-induced steatohepatitis, also known as nonalcoholic steatohepatitis (NASH). Although the etiology of these 2 conditions is different, they share pathways to disease progression and severity. They also have differences in physiologic pathways, and shared and divergent mechanisms can be therapeutic targets. There is no approved pharmacologic therapy for NASH, but several molecules are under study...
February 2019: Clinics in Liver Disease
Nitzan C Roth, Jia Qin
Excessive alcohol consumption can lead to a spectrum of liver histopathology, including steatosis, steatohepatitis, foamy degeneration, fatty liver with cholestasis, and cirrhosis. Although variability in sampling and pathologist interpretation are of some concern, liver biopsy remains the gold standard for distinguishing between steatohepatitis and noninflammatory histologic patterns of injury that can also cause the clinical syndrome of alcohol-related hepatitis. Liver biopsy is not routinely recommended to ascertain a diagnosis of alcohol-related liver disease in patients with an uncertain alcohol history, because the histologic features of alcohol-related liver diseases can be found in other diseases, including nonalcoholic steatohepatitis and drug-induced liver injury...
February 2019: Clinics in Liver Disease
Marcin Krawczyk, Dominika Maciejewska, Karina Ryterska, Maja Czerwińka-Rogowska, Dominika Jamioł-Milc, Karolina Skonieczna-Żydecka, Piotr Milkiewicz, Joanna Raszeja-Wyszomirska, Ewa Stachowska
(1) Introduction: Zonulin (ZO) has been proposed as a marker of intestinal permeability. Only a few studies have analyzed to date how diet influences the serum concentration of ZO among patients with non-alcoholic fatty liver disease (NAFLD). We performed a six-month dietetic intervention to evaluate the association between fiber intake and ZO concentration in 32 individuals with NAFLD. (2) Methods: Fiber content in the diet was estimated by Food Frequency Questionnaire (FFQ) and by analyzing 72-h nutritional diaries...
November 18, 2018: Nutrients
Wonsuk Choi, Jun Namkung, Inseon Hwang, Hyeongseok Kim, Ajin Lim, Hye Jung Park, Hye Won Lee, Kwang-Hyub Han, Seongyeol Park, Ji-Seon Jeong, Geul Bang, Young Hwan Kim, Vijay K Yadav, Gerard Karsenty, Young Seok Ju, Chan Choi, Jae Myoung Suh, Jun Yong Park, Sangkyu Park, Hail Kim
Nonalcoholic fatty liver disease (NAFLD) is increasing in worldwide prevalence, closely tracking the obesity epidemic, but specific pharmaceutical treatments for NAFLD are lacking. Defining the key molecular pathways underlying the pathogenesis of NAFLD is essential for developing new drugs. Here we demonstrate that inhibition of gut-derived serotonin synthesis ameliorates hepatic steatosis through a reduction in liver serotonin receptor 2A (HTR2A) signaling. Local serotonin concentrations in the portal blood, which can directly travel to and affect the liver, are selectively increased by high-fat diet (HFD) feeding in mice...
November 16, 2018: Nature Communications
Christian A Hudert, Heiko Tzschätzsch, Birgit Rudolph, Hendrik Bläker, Christoph Loddenkemper, Hans-Peter Müller, Stephan Henning, Philip Bufler, Bernd Hamm, Jürgen Braun, Hermann-Georg Holzhütter, Susanna Wiegand, Ingolf Sack, Jing Guo
OBJECTIVES: Today, nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in children and adults alike. Yet, the noninvasive evaluation of disease severity remains a diagnostic challenge. In this study, we apply multifrequency magnetic resonance elastography (mMRE) for the quantification of liver steatosis and fibrosis in adolescents with NAFLD. METHODS: Fifty adolescents (age range, 10-17 years; mean BMI, 33.9 kg/m; range, 21.4-42.1 kg/m) with biopsy-proven NAFLD were included in this prospective study...
November 15, 2018: Investigative Radiology
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