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https://www.readbyqxmd.com/read/28223344/an-intestinal-farnesoid-x-receptor-ceramide-signaling-axis-modulates-hepatic-gluconeogenesis-in-mice
#1
Cen Xie, Changtao Jiang, Jingmin Shi, Xiaoxia Gao, Dongxue Sun, Lulu Sun, Ting Wang, Shogo Takahashi, Mallappa Anitha, Kristopher W Krausz, Andrew D Patterson, Frank J Gonzalez
Increasing evidence supports the view that intestinal farnesoid X receptor (FXR) is involved in glucose tolerance and that FXR signaling can be profoundly impacted by the gut microbiota. Selective manipulation of the gut microbiota-FXR signaling axis was reported to significantly impact glucose intolerance, but the precise molecular mechanism remains largely unknown. Here, caffeic acid phenethyl ester (CAPE), an over-the-counter dietary supplement and an inhibitor of bacterial bile salt hydrolase, increased levels of intestinal tauro-β-muricholic acid, which selectively suppresses intestinal FXR signaling...
March 2017: Diabetes
https://www.readbyqxmd.com/read/28223285/butyrate-regulates-liver-mitochondrial-function-efficiency-and-dynamic-in-insulin-resistant-obese-mice
#2
Maria Pina Mollica, Giuseppina Mattace Raso, Gina Cavaliere, Giovanna Trinchese, Chiara De Filippo, Serena Aceto, Marina Prisco, Claudio Pirozzi, Francesca Di Guida, Adriano Lama, Marianna Crispino, Diana Tronino, Paola Di Vaio, Roberto Berni Canani, Antonio Calignano, Rosaria Meli
Fatty liver, oxidative stress, and mitochondrial dysfunction are key pathophysiological features of insulin resistance and obesity. Butyrate, produced by fermentation in the large intestine by gut microbiota, and its synthetic derivative, the N-(1-carbamoyl-2-phenyl-ethyl) butyramide, FBA, have been demonstrated to be protective against insulin resistance and fatty liver.Here, hepatic mitochondria were identified as the main target of the beneficial effect of both butyrate-based compounds in reverting insulin resistance and fat accumulation in diet induced obese mice...
February 21, 2017: Diabetes
https://www.readbyqxmd.com/read/28222147/the-desert-gerbil-psammomys-obesus-as-a-model-for-metformin-sensitive-nutritional-type-2-diabetes-to-protect-hepatocellular-metabolic-damage-impact-of-mitochondrial-redox-state
#3
Inès Gouaref, Dominique Detaille, Nicolas Wiernsperger, Naim Akhtar Khan, Xavier Leverve, Elhadj-Ahmed Koceir
INTRODUCTION: While metformin (MET) is the most widely prescribed antidiabetic drug worldwide, its beneficial effects in Psammomys obesus (P. obesus), a rodent model that mimics most of the metabolic features of human diabetes, have not been explored thoroughly. Here, we sought to investigate whether MET might improve insulin sensitivity, glucose homeostasis, lipid profile as well as cellular redox and energy balance in P. obesus maintained on a high energy diet (HED). MATERIALS AND METHODS: P...
2017: PloS One
https://www.readbyqxmd.com/read/28215579/mitochondrial-dna-maintenance-defects
#4
REVIEW
Ayman W El-Hattab, William J Craigen, Fernando Scaglia
The maintenance of mitochondrial DNA (mtDNA) depends on a number of nuclear gene-encoded proteins including a battery of enzymes forming the replisome needed to synthesize mtDNA. These enzymes need to be in balanced quantities to function properly that is in part achieved by exchanging intramitochondrial contents through mitochondrial fusion. In addition, mtDNA synthesis requires a balanced supply of nucleotides that is achieved by nucleotide recycling inside the mitochondria and import from the cytosol. Mitochondrial DNA maintenance defects (MDMDs) are a group of diseases caused by pathogenic variants in the nuclear genes involved in mtDNA maintenance resulting in impaired mtDNA synthesis leading to quantitative (mtDNA depletion) and qualitative (multiple mtDNA deletions) defects in mtDNA...
February 16, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28213291/hepatoprotective-effect-of-2-o-galloylhyperin-against-oxidative-stress-induced-liver-damage-through-induction-of-nrf2-are-mediated-antioxidant-pathway
#5
Peng Wang, Yi-Meng Gao, Xing Sun, Na Guo, Ji Li, Wei Wang, Li-Ping Yao, Yu-Jie Fu
2'-O-galloylhyperin (2'-O-GH), an active compound isolated from Pyrola calliantha, possesses remarkable antioxidant activity. The aims of this study were to investigate the hepatoprotective effect of 2'-O-GH against oxidative stress and elucidate the underlying mechanistic signaling pathways in HepG2 cells as well as in an animal model. Results showed that 2'-O-GH significantly inhibited hydrogen peroxide (H2O2)-induced HepG2 cell death in a dose dependent manner. The mitogen-activated protein kinase activation, ROS production, mitochondrial membrane potential, intracellular calcium level and subsequent apoptotic protein activation in H2O2-stimulated HepG2 cells were remarkably inhibited by 2'-O-GH...
February 16, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28205519/mitochondrial-atp-transporter-depletion-protects-mice-against-liver-steatosis-and-insulin-resistance
#6
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/28205173/measurement-of-mitochondrial-cholesterol-import-using-a-mitochondria-targeted-cyp11a1-fusion-construct
#7
Barry E Kennedy, Mark Charman, Barbara Karten
All animal membranes require cholesterol as an essential regulator of biophysical properties and function, but the levels of cholesterol vary widely among different subcellular compartments. Mitochondria, and in particular the inner mitochondrial membrane, have the lowest levels of cholesterol in the cell. Nevertheless, mitochondria need cholesterol for membrane maintenance and biogenesis, as well as oxysterol, steroid, and hepatic bile acid production. Alterations in mitochondrial cholesterol have been associated with a range of pathological conditions, including cancer, hepatosteatosis, cardiac ischemia, Alzheimer's, and Niemann-Pick Type C Disease...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28193580/astaxanthin-inhibits-inflammation-and-fibrosis-in-the-liver-and-adipose-tissue-of-mouse-models-of-diet-induced-obesity-and-nonalcoholic-steatohepatitis
#8
Bohkyung Kim, Callie Farruggia, Chai Siah Ku, Tho X Pham, Yue Yang, Minkyung Bae, Casey J Wegner, Nicholas J Farrell, Ellen Harness, Young-Ki Park, Sung I Koo, Ji-Young Lee
The objective of this study was to determine if astaxanthin (ASTX), a xanthophyll carotenoid, can prevent obesity-associated metabolic abnormalities, inflammation and fibrosis in diet-induced obesity (DIO) and nonalcoholic steatohepatitis (NASH) mouse models. Male C57BL/6J mice were fed a low-fat (6% fat, w/w), a high-fat/high-sucrose control (HF/HS; 35% fat, 35% sucrose, w/w), or a HF/HS containing ASTX (AHF/HS; 0.03% ASTX, w/w) for 30 weeks. To induce NASH, another set of mice was fed a HF/HS diet containing 2% cholesterol (HF/HS/HC) a HF/HS/HC with 0...
March 2, 2016: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28183717/the-transcriptional-regulator-of-the-chaperone-response-hsf1-controls-hepatic-bioenergetics-and-protein-homeostasis
#9
Aijun Qiao, Xiongjie Jin, Junfeng Pang, Demetrius Moskophidis, Nahid F Mivechi
Metabolic energy reprogramming facilitates adaptations to a variety of stress conditions and cellular dysfunction, but how the energetic demands are monitored and met in response to physiological stimuli remains elusive. Our data support a model demonstrating that heat shock factor 1 (HSF1), a master transcriptional regulator of the chaperone response, has been coopted from its role as a critical protein quality-control regulator to having a central role in systemic energy sensing and for metabolic adaptation to nutrient availability...
February 9, 2017: Journal of Cell Biology
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
#10
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/28177662/esculetin-induces-apoptosis-of-smmc-7721-cells-through-igf-1-pi3k-akt-mediated-mitochondrial-pathways
#11
Juan Li, Shuang Li, Xiuli Wang, Hongxin Wang
Esculetin (6,7-dihydroxycoumarin) is a coumarin derivative extracted from natural plants and has been reported to have anti-cancer activity. However, the mechanism by which esculetin prevents human hepatic cancer cell growth is still largely unknown. In this study, we investigated the effect of esculetin on human hepatocellular carcinoma (HCC) SMMC-7721 cells and explored the cell signal mechanism. Our data indicated that esculetin induced apoptosis in SMMC-7721 cells, which were supported by DAPI staining and Annexin V/PI staining...
February 3, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28174739/increased-mitochondrial-genetic-diversity-in-persons-infected-with-hepatitis-c-virus
#12
David S Campo, Ha-Jung Roh, Brian L Pearlman, Daniel S Fierer, Sumathi Ramachandran, Gilberto Vaughan, Andrew Hinds, Zoya Dimitrova, Pavel Skums, Yury Khudyakov
BACKGROUND & AIMS: The host genetic environment contributes significantly to the outcomes of hepatitis C virus (HCV) infection and therapy response, but little is known about any effects of HCV infection on the host beyond any changes related to adaptive immune responses. HCV persistence is associated strongly with mitochondrial dysfunction, with liver mitochondrial DNA (mtDNA) genetic diversity linked to disease progression. METHODS: We evaluated the genetic diversity of 2 mtDNA genomic regions (hypervariable segments 1 and 2) obtained from sera of 116 persons using next-generation sequencing...
September 2016: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28166970/effects-of-intrauterine-growth-restriction-during-late-pregnancy-on-the-cell-apoptosis-and-related-gene-expression-in-ovine-fetal-liver
#13
Yingchun Liu, Chi Ma, Hui Li, Lingyao Li, Feng Gao, Changjin Ao
This study investigated the effect of intrauterine growth restriction (IUGR) during late pregnancy on the cell apoptosis and related gene expression in ovine fetal liver. Eighteen time-mated Mongolian ewes with singleton fetuses were allocated to three groups at d 90 of pregnancy: Restricted Group 1 (RG1, 0.18 MJ ME kg BW(-0.75) d(-1), n = 6), Restricted Group 2 (RG2, 0.33 MJ ME kg BW(-0.75) d(-1), n = 6) and a Control Group (CG, ad libitum, 0.67 MJ ME kg BW (-0.75) d (-1), n = 6). Fetuses were recovered at slaughter on d 140...
March 1, 2017: Theriogenology
https://www.readbyqxmd.com/read/28165879/resveratrol-prevents-ammonia-induced-mitochondrial-dysfunction-and-cellular-redox-imbalance-in-c6-astroglial-cells
#14
Larissa Daniele Bobermin, Diogo Onofre Souza, Carlos-Alberto Gonçalves, André Quincozes-Santos
BACKGROUND: Resveratrol is a polyphenolic compound that presents several protective effects in the central nervous system, including gliotoxicity associated to hyperammonemia, a key element for the development of hepatic encephalopathy. In this condition, mitochondrial dysfunction leads to a reactive oxygen species (ROS) overproduction, which, in turn, exacerbates mitochondrial failure and causes cellular damage. OBJECTIVE: This study sought to determine whether prevention of mitochondrial dysfunction and the maintenance of cellular redox status by resveratrol contribute to its protective action toward ammonia toxicity...
February 6, 2017: Nutritional Neuroscience
https://www.readbyqxmd.com/read/28165481/targeting-mitochondrial-dysfunction-can-restore-antiviral-activity-of-exhausted-hbv-specific-cd8-t-cells-in-chronic-hepatitis-b
#15
Paola Fisicaro, Valeria Barili, Barbara Montanini, Greta Acerbi, Manuela Ferracin, Francesca Guerrieri, Debora Salerno, Carolina Boni, Marco Massari, M Cristina Cavallo, Glenda Grossi, Tiziana Giuberti, Pietro Lampertico, Gabriele Missale, Massimo Levrero, Simone Ottonello, Carlo Ferrari
Hepatitis B virus (HBV)-specific CD8 T cells are functionally exhausted in chronic hepatitis B infection, and this condition can be corrected only partially through the modulation of inhibitory pathways, which suggests that a more complex molecular interplay underlies T cell exhaustion. To gain broader insight into this process and identify additional targets for the restoration of T cell function, we compared the transcriptome profiles of HBV-specific CD8 T cells from patients with acute and chronic disease with those of HBV-specific CD8 T cells from patients able to resolve HBV infection spontaneously and influenza (FLU)-specific CD8 T cells from healthy participants...
February 6, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28161417/celastrol-attenuates-mitochondrial-dysfunction-and-inflammation-in-palmitate-mediated-insulin-resistance-in-c3a-hepatocytes
#16
Mohamad Hafizi Abu Bakar, Mohamad Roji Sarmidi, Joo Shun Tan, Mohamad Norisham Mohamad Rosdi
Accumulating evidence indicates that mitochondrial dysfunction-induced inflammation is among the convergence points for the greatest hallmarks of hepatic insulin resistance. Celastrol, an anti-inflammatory compound from the root of Tripterygium Wilfordii has been reported to mitigate insulin resistance and inflammation in animal disease models. Nevertheless, the specific mechanistic actions of celastrol in modulating such improvements at the cellular level remain obscure. The present study sought to explore the mechanistic roles of celastrol upon insulin resistance induced by palmitate in C3A human hepatocytes...
February 1, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28159595/a-35%C3%A2-kda-phyllanthus-niruri-protein-suppresses-indomethacin-mediated-hepatic-impairments-its-role-in-hsp70-ho-1-jnks-and-ca-2-dependent-inflammatory-pathways
#17
Sudip Bhattacharyya, Sharmistha Banerjee, Chirajyoti Guha, Shatadal Ghosh, Parames C Sil
The present study has been conducted to explore a novel strategy to modulate the unfavourable effects of indomethacin by Phyllanthus niruri protein (PNP) and the underlying mechanism PNP exploits for the amelioration of that pathophysiology. In hepatocytes, indomethacin enhanced reactive oxygen species (ROS), reduced intracellular antioxidant capacity, up regulated mitogen activated protein kinase (MAPKs), disrupted mitochondrial membrane potential, activated apoptotic pathways and there by reduced the viability of the hepatocytes...
January 31, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28151934/hepatitis-b-virus-modulates-store-operated-calcium-entry-to-enhance-viral-replication-in-primary-hepatocytes
#18
Jessica C Casciano, Nicholas J Duchemin, R Jason Lamontagne, Laura F Steel, Michael J Bouchard
Many viruses modulate calcium (Ca2+) signaling to create a cellular environment that is more permissive to viral replication, but for most viruses that regulate Ca2+ signaling, the mechanism underlying this regulation is not well understood. The hepatitis B virus (HBV) HBx protein modulates cytosolic Ca2+ levels to stimulate HBV replication in some liver cell lines. A chronic HBV infection is associated with life-threatening liver diseases, including hepatocellular carcinoma (HCC), and HBx modulation of cytosolic Ca2+ levels could have an important role in HBV pathogenesis...
2017: PloS One
https://www.readbyqxmd.com/read/28148899/regulation-of-hepatic-pyruvate-dehydrogenase-phosphorylation-in-offspring-glucose-intolerance-induced-by-intrauterine-hyperglycemia
#19
Yong Zhang, Ying Zhang, Guo-Lian Ding, Xin-Mei Liu, Jianping Ye, Jian-Zhong Sheng, Jianxia Fan, He-Feng Huang
AIM: Gestational diabetes mellitus (GDM) has been shown to be associated with a high risk of diabetes in offspring. In mitochondria, the inhibition of pyruvate dehydrogenase (PDH) activity by PDH phosphorylation is involved in the development of diabetes. We aimed to determine the role of PDH phosphorylation in the liver in GDM-induced offspring glucose intolerance. RESULTS: PDH phosphorylation was increased in lymphocytes from the umbilical cord blood of the GDM patients and in high glucose-treated hepatic cells...
January 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28146130/effects-of-natural-products-on-fructose-induced-nonalcoholic-fatty-liver-disease-nafld
#20
REVIEW
Qian Chen, Tingting Wang, Jian Li, Sijian Wang, Feng Qiu, Haiyang Yu, Yi Zhang, Tao Wang
As a sugar additive, fructose is widely used in processed foods and beverages. Excessive fructose consumption can cause hepatic steatosis and dyslipidemia, leading to the development of metabolic syndrome. Recent research revealed that fructose-induced nonalcoholic fatty liver disease (NAFLD) is related to several pathological processes, including: (1) augmenting lipogenesis; (2) leading to mitochondrial dysfunction; (3) stimulating the activation of inflammatory pathways; and (4) causing insulin resistance...
January 31, 2017: Nutrients
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