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Fatty liver disease treatment

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https://www.readbyqxmd.com/read/28209927/improved-health-span-and-lifespan-in-mtdna-mutator-mice-treated-with-the-mitochondrially-targeted-antioxidant-skq1
#1
Irina G Shabalina, Mikhail Yu Vyssokikh, Natalia Gibanova, Robert I Csikasz, Daniel Edgar, Anne Hallden-Waldemarson, Zinaida Rozhdestvenskaya, Lora E Bakeeva, Valeria B Vays, Antonina V Pustovidko, Maxim V Skulachev, Barbara Cannon, Vladimir P Skulachev, Jan Nedergaard
MtDNA mutator mice exhibit marked features of premature aging. We find that these mice treated from age of ≈100 days with the mitochondria-targeted antioxidant SkQ1 showed a delayed appearance of traits of aging such as kyphosis, alopecia, lowering of body temperature, body weight loss, as well as ameliorated heart, kidney and liver pathologies. These effects of SkQ1 are suggested to be related to an alleviation of the effects of an enhanced reactive oxygen species (ROS) level in mtDNA mutator mice: the increased mitochondrial ROS released due to mitochondrial mutations probably interact with polyunsaturated fatty acids in cardiolipin, releasing malondialdehyde and 4-hydroxynonenal that form protein adducts and thus diminishes mitochondrial functions...
February 15, 2017: Aging
https://www.readbyqxmd.com/read/28205519/mitochondrial-atp-transporter-depletion-protects-mice-against-liver-steatosis-and-insulin-resistance
#2
Joonseok Cho, Yujian Zhang, Shi-Young Park, Anna-Maria Joseph, Chul Han, Hyo-Jin Park, Srilaxmi Kalavalapalli, Sung-Kook Chun, Drake Morgan, Jae-Sung Kim, Shinichi Someya, Clayton E Mathews, Young Jae Lee, Stephanie E Wohlgemuth, Nishanth E Sunny, Hui-Young Lee, Cheol Soo Choi, Takayuki Shiratsuchi, S Paul Oh, Naohiro Terada
Non-alcoholic fatty liver disease (NAFLD) is a common metabolic disorder in obese individuals. Adenine nucleotide translocase (ANT) exchanges ADP/ATP through the mitochondrial inner membrane, and Ant2 is the predominant isoform expressed in the liver. Here we demonstrate that targeted disruption of Ant2 in mouse liver enhances uncoupled respiration without damaging mitochondrial integrity and liver functions. Interestingly, liver specific Ant2 knockout mice are leaner and resistant to hepatic steatosis, obesity and insulin resistance under a lipogenic diet...
February 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/28196718/the-neuropeptide-galanin-is-up-regulated-during-cholestasis-and-contributes-to-cholangiocyte-proliferation
#3
Matthew McMillin, Gabriel Frampton, Stephanie Grant, Sharon DeMorrow
During the course of cholestatic liver diseases, mitotically dormant cholangiocytes proliferate and subsequently acquire a neuroendocrine phenotype. Galanin is a neuroendocrine factor responsible for regulation of physiological responses, such as feeding behavior and mood, and has been implicated in the development of fatty liver disease, although its role in biliary hyperplasia is unknown. Biliary hyperplasia was induced in rats via bile duct ligation (BDL) surgery, and galanin was increased in serum and liver homogenates from BDL rats...
February 11, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28190475/calycosin-attenuates-triglyceride-accumulation-and-hepatic-fibrosis-in-murine-model-of-non-alcoholic-steatohepatitis-via-activating-farnesoid-x-receptor
#4
Xingping Duan, Qiang Meng, Changyuan Wang, Zhihao Liu, Qi Liu, Huijun Sun, Pengyuan Sun, Xiaobo Yang, Xiaokui Huo, Jinyong Peng, Kexin Liu
BACKGROUND: Non-alcoholic steatohepatitis (NASH) represents the more severe end of hepatic steatosis and is associated with progressive liver disease. Calycosin, derived from the root of Radix Astragali, has been demonstrated to have favorable efficacy on acute liver injury. PURPOSE: The present study was to investigate the hepatoprotective effect of calycosin on attenuating triglyceride accumulation and hepatic fibrosis, as well as explore the potential mechanism in murine model of NASH...
February 15, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/28187366/a-combination-of-dietary-n-3-fatty-acids-and-a-cyclooxygenase-1-inhibitor-attenuates-nonalcoholic-fatty-liver-disease-in-mice
#5
Viswanathan Saraswathi, Curtis Perriotte-Olson, Murali Ganesan, Cyrus V Desouza, Yazen Alnouti, Michael J Duryee, Geoffrey M Thiele, Tara M Nordgren, Dahn L Clemens
We sought to determine whether a combination of purified n-3 fatty acids (n-3) and SC-560 (SC), a cyclooxygenase-1-specific inhibitor, is effective in ameliorating nonalcoholic fatty liver disease in obesity. Female wild-type mice were fed a high-fat and high-cholesterol diet (HF) supplemented with n-3 in the presence or absence of SC. Mice treated with SC alone exhibited no change in liver lipids, whereas n-3-fed mice tended to have lower hepatic lipids. Mice given n-3+SC had significantly lower liver lipids compared with HF controls indicating enhanced lipid clearance...
January 27, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28185715/effects-of-oral-antidiabetic-drugs-on-changes-in-the-liver-to-spleen-ratio-on-computed-tomography-and-inflammatory-biomarkers-in-patients-with-type-2-diabetes-and-nonalcoholic-fatty-liver-disease
#6
Koichi Yabiku, Akiko Mutoh, Kazufumi Miyagi, Nobuyuki Takasu
PURPOSE: Oral antidiabetic drugs (OADs) such as pioglitazone and metformin have beneficial effects in patients with nonalcoholic steatohepatitis. We prospectively assessed the effects of OADs on nonalcoholic fatty liver disease (NAFLD) in 886 men with type 2 diabetes mellitus and in a murine model of NAFLD. METHODS: Patients were randomized to receive pioglitazone, metformin, sitagliptin, or a non-OAD (control) for 6 months. All the patients received dietary and exercise guidance once a month during this study...
February 6, 2017: Clinical Therapeutics
https://www.readbyqxmd.com/read/28183232/triterpenoids-and-polysaccharide-peptides-enriched-ganoderma-lucidum-a-randomized-double-blind-placebo-controlled-crossover-study-of-its-antioxidation-and-hepatoprotective-efficacy-in-healthy-volunteers
#7
Hui-Fang Chiu, Hui-Yu Fu, Yan-Ying Lu, Yi-Chun Han, You-Cheng Shen, Kamesh Venkatakrishnan, Oksana Golovinskaia, Chin-Kun Wang
CONTEXT: Ganoderma lucidum (Leyss: Fr) Karst. (Polyporaceae) is an oriental medicinal fungus, commonly used in traditional Chinese medicine (TCM) for treating various condition or diseases such as hypertension, hyperglycaemia, hepatitis and cancer. OBJECTIVE: The current study examines whether triterpenoids and polysaccharide-enriched G. lucidum (GL) influence antioxidation and hepatoprotective efficacy by suppressing oxidative stress. MATERIALS AND METHODS: Forty-two healthy subjects (22 male and 20 female) were recruited and segregated into two groups as experimental or placebo and requested to intake GL (n = 21) or placebo (n = 21) capsule (225 mg; after lunch or dinner) for six consecutive months and vice versa with one month washout period in between...
December 2017: Pharmaceutical Biology
https://www.readbyqxmd.com/read/28182612/non-alcoholic-fatty-liver-disease-in-hiv-infection
#8
Juan Macías, Juan A Pineda, Luis M Real
Non-alcoholic fatty liver disease is one of the most frequent chronic hepatic conditions worldwide. The spectrum of non-alcoholic fatty liver disease goes from hepatic steatosis to steatohepatitis, cirrhosis, and hepatocellular carcinoma. Risk factors for non-alcoholic fatty liver disease are metabolic, mainly obesity and the accompanying consequences. Treatment and prevention of non-alcoholic fatty liver disease should target those metabolic abnormalities. The frequency of and the factors associated with hepatic steatosis in HIV infection seem to be similar to those reported in the general population, though direct comparisons are lacking...
January 2017: AIDS Reviews
https://www.readbyqxmd.com/read/28181781/thyroid-dysfunction-and-nonalcoholic-fatty-liver-disease
#9
Zoe A Efstathiadou, Marina D Kita, Stergios A Polyzos
Thyroid hormones are crucial for hepatic lipid and glucose metabolism. Nonalcoholic fatty liver disease (NAFLD), a very common and potentially serious disease of modern society, shares common clinical features with hypothyroidism, such as obesity, insulin resistance and dyslipidemia. Furthermore, in certain studies, increased prevalence of hypothyroidism was observed in patients with NAFLD. However, whether there is a linear relationship between thyroid hormone levels and NAFLD incidence and severity, including values within or in proximity to the reference range remains a contradictory subject in the literature...
February 9, 2017: Minerva Endocrinologica
https://www.readbyqxmd.com/read/28178326/quantitative-liver-proteomics-identifies-fgf19-targets-that-couple-metabolism-and-proliferation
#10
Vittoria Massafra, Alexandra Milona, Harmjan R Vos, Boudewijn M T Burgering, Saskia W C van Mil
Fibroblast growth factor 19 (FGF19) is a gut-derived peptide hormone that is produced following activation of Farnesoid X Receptor (FXR). FGF19 is secreted and signals to the liver, where it contributes to the homeostasis of bile acid (BA), lipid and carbohydrate metabolism. FGF19 is a promising therapeutic target for the metabolic syndrome and cholestatic diseases, but enthusiasm for its use has been tempered by FGF19-mediated induction of proliferation and hepatocellular carcinoma. To inform future rational design of FGF19-variants, we have conducted temporal quantitative proteomic and gene expression analyses to identify FGF19-targets related to metabolism and proliferation...
2017: PloS One
https://www.readbyqxmd.com/read/28177674/exercise-restores-bioavailability-of-hydrogen-sulfide-and-promotes-autophagy-influx-in-livers-of-mice-fed-with-high-fat-diet
#11
Bing Wang, Jing Zeng, Qi Gu
In the gold standard treatment for non-alcoholic fatty liver disease (NAFLD), exercise training has been shown to effectively improve NASH. However, limited data are available about the underlying mechanisms involved. This work was undertaken to investigate the mechanisms underlying the beneficial effect of exercise training on high-fat diet (HFD)-induced NAFLD in mice. Male mice were fed with HFD and given moderate-intensity exercise for 24 weeks. Exercise training lowered weight gain, attenuated systemic insulin resistance and glucose intolerance, mitigated hepatic steatosis and fibrosis in mice fed with HFD...
January 10, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28176894/autoimmune-hepatitis-current-challenges-and-future-prospects
#12
REVIEW
Yoshio Aizawa, Atsushi Hokari
Autoimmune hepatitis (AIH) is a chronic progressive liver disease characterized by high levels of aminotransferases and autoantibodies, hypergammaglobulinemia, and interface hepatitis. AIH affects all races and all ages worldwide, regardless of sex, although a preponderance of females is a constant finding. The etiology of AIH has not been completely elucidated, but immunogenetic background and environmental parameters may contribute to its development. The most important genetic factor is human leukocyte antigens (HLAs), especially HLA-DR, whereas the role of environmental factors is not completely understood...
2017: Clinical and Experimental Gastroenterology
https://www.readbyqxmd.com/read/28169366/phytosterol-esters-attenuate-hepatic-steatosis-in-rats-with-non-alcoholic-fatty-liver-disease-rats-fed-a-high-fat-diet
#13
Lihua Song, Dan Qu, Qing Zhang, Jing Jiang, Haiyue Zhou, Rui Jiang, Yating Li, Yao Zhang, Hongli Yan
Given the adverse effects of drugs used for NAFLD treatment, identifying novel and effective natural compound to prevent NAFLD is urgently needed. In the present study, the effects of phytosterol esters (PSEs) on NAFLD were explored. Adult SD rats were randomized into five groups: normal chow diet (NC), high-fat diet (HF), low-, medium- and high-dose PSE treatment plus high-fat diet groups (PSEL, PSEM, and PSEH). Our results showed that the levels of LDL-C in the PSEL group and hepatic TG, TC, and FFA in the three PSEs groups were significantly decreased...
February 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28167804/mir-29a-modulates-scd-expression-and-is-regulated-in-response-to-a-saturated-fatty-acids-diet-in-juvenile-gift-oreochromis-niloticus
#14
Jun Qiang, Yi Fan Tao, Jie He, Yi Lan Sun, Pao Xu
MicroRNAs (miRNAs) are small non-coding RNAs that regulate target gene expression by binding to the 3'untranslated region (3'UTR) of the target mRNA. MiRNAs regulate a large variety of genes, including those involved in liver biology and disease. Here, we report for the first time that miR-29a post-transcriptionally regulates stearoyl-CoA desaturase (SCD) by binding to its 3'UTR in genetically improved farmed tilapia (GIFT), Oreochromis niloticus, as shown by a 3'UTR luciferase reporter assay. miR-29a antagomir treatment in vivo resulted in significant up-regulation of SCD expression...
February 6, 2017: Journal of Experimental Biology
https://www.readbyqxmd.com/read/28167322/-nlrp3-inflammasome-blockade-reduces-liver-inflammation-and-fibrosis-in-experimental-nash-in-mice
#15
Auvro R Mridha, Alexander Wree, Avril A B Robertson, Matthew M Yeh, Casey D Johnson, Derrick M Van Rooyen, Fahrettin Haczeyni, Narci C-H Teoh, Christopher Savard, George N Ioannou, Seth L Masters, Kate Schroder, Matthew A Cooper, Ariel E Feldstein, Geoffrey C Farrell
BACKGROUND AND AIMS: NOD-like receptor protein 3 (NLRP3) inflammasome activation occurs in NAFLD. We used the first small molecule NLRP3 inhibitor, MCC950, to test whether inflammasome blockade alters inflammatory recruitment and liver fibrosis in two murine models of steatohepatitis. METHODS: We fed foz/foz and wildtype (Wt) mice atherogenic diet 16 weeks, gavaged MCC950 or vehicle until 24 weeks, then determining NAFLD phenotype. In mice fed methionine/choline deficient (MCD) diet, we gavaged MCC950 or vehicle 6 weeks and determined effects on liver fibrosis...
February 3, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28164196/preventive-effect-of-silibinin-in-combination-with-pu-erh-tea-extract-on-non-alcoholic-fatty-liver-disease-in-ob-ob-mice
#16
Wen-Yi Hu, Xiao-Hui Ma, Wang-Yi Zhou, Xin-Xin Li, Ting-Ting Sun, He Sun
There are presently no miracle drugs for non-alcoholic fatty liver disease (NAFLD). This study investigates the synergistic effect of Silibinin combined with Pu-erh tea extract (PTE) against NAFLD and explores the suggested mechanism of action. Ob/ob mice were fed a high fat diet along with the oral administration of Silibinin (86 mg per kg per day), PTE (250 mg per kg per day) or their combination for 6 weeks. Their lean littermates who were fed with standard chow diet were used as the control group. The blood biochemical index and histopathological evaluation were analyzed...
February 6, 2017: Food & Function
https://www.readbyqxmd.com/read/28163820/apolipoprotein-ciii-overexpression-induced-hypertriglyceridemia-increases-nonalcoholic-fatty-liver-disease-in-association-with-inflammation-and-cell-death
#17
Adriene A Paiva, Helena F Raposo, Amarylis C B A Wanschel, Tarlliza R Nardelli, Helena C F Oliveira
Nonalcoholic fatty liver disease (NAFLD) is the principal manifestation of liver disease in obesity and metabolic syndrome. By comparing hypertriglyceridemic transgenic mice expressing apolipoprotein (apo) CIII with control nontransgenic (NTg) littermates, we demonstrated that overexpression of apoCIII, independent of a high-fat diet (HFD), produces NAFLD-like features, including increased liver lipid content; decreased antioxidant power; increased expression of TNFα, TNFα receptor, cleaved caspase-1, and interleukin-1β; decreased expression of adiponectin receptor-2; and increased cell death...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28161092/fatty-acid-and-non-alcoholic-fatty-liver-disease-meta-analyses-of-case-control-and-randomized-controlled-trials
#18
Xiao-Fei Guo, Bo Yang, Jun Tang, Duo Li
BACKGROUND AND AIMS: Blood and/or liver fatty acid contents of healthy subjects and non-alcoholic fatty liver disease (NAFLD) patients have shown inconsistent associations. In addition, the results of randomized controlled trials (RCTs) in relation to the effects of n-3 polyunsaturated fatty acid (PUFA) supplementation on alanine aminotransferase (ALT), aspartate aminotransferase (AST), liver fat, triglyceride (TAG) and fasting glucose levels are inconsistent. The present study aimed to investigate the differences of fatty acid content in the blood and/or liver tissue between healthy subjects and NAFLD patients, and to quantify the benefits of n-3 PUFA therapy in NAFLD patients...
January 16, 2017: Clinical Nutrition: Official Journal of the European Society of Parenteral and Enteral Nutrition
https://www.readbyqxmd.com/read/28160250/thiopurines-and-methotrexate-use-in-ibd-patients-in-a-biologic-era
#19
REVIEW
Gerassimos J Mantzaris
Although we have been living in the era of biologic therapy for several decades, the use of immunomodulators (primarily thiopurines [azathioprine and mercaptopurine] and less so methotrexate) still remains an important component of the inflammatory bowel disease (IBD) pharmaceutical arsenal. Thiopurines as monotherapy exert corticosteroid-sparing effects and can maintain long-term remission in a considerable proportion of patients who have frequent relapses and are or have become mesalazine and/or corticosteroid intolerant or refractory...
February 3, 2017: Current Treatment Options in Gastroenterology
https://www.readbyqxmd.com/read/28159867/fenofibrate-but-not-ezetimibe-prevents-fatty-liver-disease-in-mice-lacking-phosphatidylethanolamine-n-methyltransferase
#20
Jelske N van der Veen, Susanne Lingrell, Xia Gao, Abhijit Takawale, Zamaneh Kassiri, Dennis E Vance, René L Jacobs
BACKGROUND AND AIMS: Mice lacking phosphatidylethanolamine N-methyltransferase (PEMT) are protected from high-fat diet (HFD)-induced obesity and insulin resistance. However, these mice develop severe non-alcoholic fatty liver disease (NAFLD) when fed the HFD, which is mainly due to inadequate secretion of VLDL particles. Our aim was to prevent NAFLD development in mice lacking PEMT. METHODS: We treated Pemt-/- mice with either ezetimibe or fenofibrate to see if either could ameliorate liver disease in these mice...
February 3, 2017: Journal of Lipid Research
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